PATHO - Reproductive System Flashcards
Female gametes are known as ____________.
Male gemetes are known as __________.
Each gamete contains _____ chromosomes. Female x male gametes unite together to form a ____ chromosome zygote.
Female gamete: ovum
Male gamete: spermatozoon (sperm cell)
Each gamete: 23 chromosomes
Joins together to form a 46 chromosome zygote
Classification of sex hormones
steroid hormones
all made from cholesterol
Function of dehydroepiandrosterone (DHEA) in females and males
- from adrenal gland, ovary, other tissues
- Females & Males : converted to androstenedione ⇒ estrogens, testosterone, both
Function of estrogens in females and males
- estrone, estradiol, estriol - works on estrogen receptors 𝝰 & 𝛃 (in ovary and placenta, small amounts in other tissues)
-
Females: stimulates development of female sex traits:
- breast, uterus, and vaginal maturation
- proliferation of endometrium during menstrual cycle
- mammary gland development during pregnancy
- promotes fetal adrenal gland function
- uteroplacental blood flow
- Males: growth at puberty, fusion of bone growht plate, preventing apoptosis of germ cells
Source and function of testosterone in females and males
- Source: adrenal glands (from DHEA), ovaries
- Females: libido, learning, sleep, protein anabolism, growth of muscle and bone, pubic and axillary hair, activation of sebaceous glands, contributes to acne
- Males: stimulates spermatogenesis, development of 1’ and 2’ sex tracts, bone and muscle growth, pubic and axillary hair, activates sebaceous glands, contributes to acne, maintains libido
Source and function of GnrH in females and males
- Source: neuroendocrine cells in hypothalamus
- Females & males: stimulates secretion of gonadotropins (FSH an dLH) from anterior pituitary
Source and function of FSH in females and males
- Source: gonadotroph cells from anterior pituitary
- Females: promotes development of ovarian follicles, stimulates estrogen secretion
- Males: promotes development of testes, stimulates spermatogenesis by Sertoli cells
Source and function of LH in females and males
- Source: gonadotroph cells in anterior pituitary
- Females: triggers ovulation; rpomotes development of corpus luteum
- Males: stimulates testosterone production by Leydig cells of testes
Source and Function of Inhibin in females and males
- Source: ovary and testes
-
Females & Males: inhibits FSH production in anterior pituitary
- in females, Inhibin B is primarily secreted in follicular phase but spikes when ovulation occurs
- Inhibin A is secreted during luteal phase and further supresses FSH
- also restrains prolactin and GH release, inteferes with GnRH receptors, and promotes breakdown of itnracellular gonadotropins
- activity boosted by follistatin
Source and Function of Human Chorionic Gonadotropin (hCG) in females
- Source: placenta
- Females: supports corpus luteum, which secretes estrogen and progesterone during first 7 weeks of pregnancy
Source and function of Activin in females
- Source: ovary (granulosa cells)
- Females: stimulates secretion of FSH and pituitary response to GnRH and FSH binding in dominant granulosa cells
- inhibited by follistatin
Source and Function of progesterone in females
- Source: ovary and placenta
- Females:
- promotes secretory changes in endometrium during luteal phase of menstrual cycle
- quiets uterine muscle activity
- prevents lactogenesis during pregnancy
Source and function of relaxin
Source: corpus luteum, myometrium (uterine muscle), placenta
Function: inhibits uterine contractions during pregnancy and soften pelvic joints and cervix to facilitate childbirth
In early embryonic development, the reproductive structures of male and female embryos are ____________.
They consist of a pair of primary sex organs known as ________ and two pairs of ducts which are _____________ and _____________.
In early embryonic development, the reproductive structures of male and female embryos are homologous (the same)/undifferentiated.
They consist of a pair of primary sex organs known as gonads and two pairs of ducts which are mesonephric (wolffian) and paramesonephric (müllerian) ducts.
What are the mullerian ducts?
How may these ducts change in females vs males?
- precursors of the internal female sex organs (oviducts, uterus, cervix, upper vagina)
- initially formed regardles sof genotypic sex (no SRY signaling needed for development)
- SRY signaling is needed in males for these ducts to regress and prevents deelopment of female reproductive tract
What are wolffian ducts? What is their function?
precursor of male internal sex organs
secretes testosterone and promotes development of male sex organs
The first sign of development of reproductive organs (male/female) occurs during _____ week of gestation.
5th
What kind of effect does the SRY gene have on embryonic differentiation?
- sex-determining region of the Y chromosome
Where is Muwllerian inhibitory hormone (MIF) secreted from?
What is the function of Muwllerian inhibitory hormone (MIF) in reproductive development?
Source: secreted by Sertoli cells in the testes
Function: promotes degeneration of the müllerian ducts
- No MIF, the müllerian ducts would develop and wolffian ducts would degenerate with loss of male sex organ development
At what age would the male gonads (testes) descend into the scotum?
At what age would the testes produce sperm?
Descend into the scrotum: 9 months
Sperm production: after puberty
How does female gonadal development occur?
- development occurs due to absence of SRY expression
- estrogen is present while testosterone and MIF are absent which lead to loss of wolffian system; also promotes development of external genitalia
- 6-8 weeks’ gestation: two female gonads develop into ovaries
- mesonephric ducts deteriorate and upper ends of paramesonephric ducts decome fallopian tubes
Where do external reproductive structures stem from and how do they develop from these precursor structures?
Source: homologous embyronic tissues (i.e. undifferentiated)
Development: at 7-8 weeks gestation, the male & female embryos develop genital tubercle (elevated structure). The tubercle relies on testosterone for differentiation into external male genitalia or else female genitalia will develop in the absence of ovaries
Describe when and what occurs during development of the endocrine system in utero that contributes to sexual differentiation.
4/5 weeks gestation: anterior pituitary development begins
10 weeks: GnRH produced in hypothalamus - contraols production of LH and FSH in anterior pituitary
12 weeks: vascular connection between hypothalamus and pituitary is established
28 weeks: in female fetus, high levels of FSH and LH are excreted (up until 28 weeks) and stimulate production of estrogen and progesterone by the ovary. At ~28 weeks, etrogen and progesterone levels in ovaries and placenta are high enough so gonadotropin production decreases
Females:
Production of ova occurs (during fetal life/at puberty).
How many female gametes mature per menstrual cycle?
Males:
Production of sperm occurs (during fetal life/at puberty).
How many sperm are produced daily?
Females:
ova production occurs during fetal life
one female gamete matures per menstrual cycle
Males:
sperm production occurs at puberty
Millions are produced daily, for life
What negative feedback system develops to regulate reproductive hormones?
- present at term pregnancy
- includes gonadostat (gonadotropin-releasing hormone pulse generator) that responds to high levels of placental estrogens by releasing low levels of GnRH
- After birth, steroid hormone level drops (due to loss of maternal placental hormones)
- GnRH is secreted from hypothalamus and LH and FSH are released
- in boys: peaks at 3-6 mos and then falls
- in girls: peaks at 12-18 mos and then falls
- gonadotropins are suppressed until the onset of puberty
Puberty vs Adolescence
Puberty: onset of sexual maturation (different from adolescence) - marked by development of secondary sex characteristics, rapid growth, and ability to reproduce
- Girls: begins ~8-9 y.o. with breast development (therlarche), ends with first ovulatory menstrual period in females (which can take up to 1-2 years after menarche)
- Boys: begins ~11 y.o. but may occur ealier with increased weight and BMI, begins with voice changes and ends with first ejaculation with mature sperm
- Complete when an individual is capable of reproduction
Adolescence: developmental stage between childhood and adulthood
Factors that influence puberty
- genetics
- environment
- ethnicity
- general health
- earlier onset in obese girls
- delayed with low body fat and reduced weight/intense exercise
- nutrition
What physiological/hormonal changes occur with reproductive maturation in girls (i.e. puberty)?
- ~ 1 year before puberty, there are nocturnal pulses of LH and FSH and increased response to GnRH which stimulate gonadal maturation (gonadarche) with estradiol secretion
- estradiol causes breast development (thelarche), maturation of sex organs (vagine, uterus, ovaries), and fat deposition in the hips
- estrogen and increased groth factor production causes rapid skeletal growth
- ovaries start to release matura ova
Adrenarche
- increased production of androgens (from adrenal gland)
- dehydroepiandrosterone
- androstenedione
- these are converted to testosterone and estrogen before puberty
- S/S: hair growth in armpits and pubic area, sweat and sebaceous gland activation
What physiological/hormonals changes occur during reproductive maturation in males (i.e. during puberty)?
- ~ 1 year before puberty, there are nocturnal pulses of LH and FSH and increased response to GnRH which stimulate gonadal maturation (gonadarche) with testosterone secretion
- estrogen and increased growth factor production causes rapid skeletal growth
- Testosterone causes growth of testes, scrotum, penis
- +ve feedback loop of gonadotropins stimulating gonads to produce more sex hormones
- with males, testes begin producing more mature sperm (that can fertilize ovum)
Function of the female reproductive system?
Function of external genitalia?
Overall function: to produce mature ova. provide protection and nourishment to fetus until birth
Function of external genitalia: protect body openings, involved in sexual functioning
What are the major extenal genitalia structures (6) in females?
known collectively as the vulva/pudendum
- Mons pubis
- Labia majoraa
- Labia minora
- Clitoris
- Vestibule
- Perineum
Structure and function of the mons pubis
Structure: fatty tissue layer over pubis symphysis. Gets covered in pubic hair has more active sebaceous/sweat glands during puberty
- moundlike shape due to fat deposition under the skin (caused by estrogen)
Function: protects the pubic symphysis during sexual intercourse
Structure and function of Labia Majora/majus
Structure: two folds of skin extending from mons pubis to fourchette (see diagram) to form a cleft
- During puberty: increased fatty tissue, pubic hair on lateral surfaces, and secretion of lubricants from sebaceous glands on medial surface
- ++sensitive to temperature, touch, pressure, and pain
- homologous to the male scrotum
Function: protects inner structures of vulva
Structure and Function of labia minora/minus
Structure: two smaller, thinner, asymmetric folds of skin within labia majora; forms the clitoral hood (prepuce) and frenulum. Splits to enclose the vestibule and then converge near anus to form fourchette
- hairless, pink, and moist
- well supplied by nerves, blood vessels, and sebaceous glands
Function: sebaceous glands secrete bactericidal fluid that lubricates and waterproofs vulva skin. Labia swell with blood during sexual arousal
Structure and Function of clitoris
Structure: the erectile organ betweeen the labia minora. Small and cylindrical with a visible glans and shaft that lies beneath the skin
- homologous to the penis
Function: major site for sex stimulation and orgasm. Slightly enlarges when it is filled with blood during sexual arousal
Structure and Function of vestibule & associated glands in that area
Structure: area that is protected by labia minora, contains the external opening of the vagina (introitus/vaginal orifice) and urethral opening (urinary meatus). Introitus may also be covered by hymen (thin perforated membrane)
- openings are lubricated by two pairs of glands - Skene glands, Bartholin glands
- Skene glands: aka lesser vestibular/paraurethral glands - has ducts that open on both sides of the urinary meatus. Lubricates urinary meatus
- Bartholin glands: aka greater vestibular/vulvovaginal glands - has ducts that open on either side of introitus. Secrete mucus to lubrivate inner labial surfaces and enhance viability and motility of sperm
Function: tissue underneath vestibule fills with blood and becomes engorged during sexual excitement. Secretions from the ^ glands facilitate sex
Structure of perineum
Structure: area between vaginal orifice and anus. Has less hair, skin, and subQ tissue (so skin is clsoe to underlying muscles).
- Covers the muscular perineal body - a fibrous structure that consists of elastic fibers and connective tissue & is the common attachment point for bulbocavernosus, external anal sphincter, and levator ani muscles
- varies in length (2-5cm +), has elastic properties
- length and elasticity of perineal body influences tissue resistance and injury during childbirth
What are the major internal reproductive organs in females?
ovaries
fallopian tubes
uterus
vagina
What is the structure of the vagina? What are the four layers it consists of?
Structure: an elastric & fibromuscular canal 9-10cm long. Extends up and backwards from the introitus to the lower portion of the uterus
- upper part surrounds the cervix
- Fornix: space around the cervix that is further divided into posterior (deeper) and anterior fornix - occurs due to cervix meeting the vaginal canal at a 90 deg angle
- lengthens, widens, and anterior 1/3rd becomes congested with blood during sexual excitement
Vaginal wall has 4 layers:
- 1) Mucous membrane lining of squamous epithelial cells - thickens and thins in response to hormones (i.e. estrogen). In those that are of reproductive age, this layer is arranged in transverse wrinkles (rugae_)_ that allows stretching during coitus and childbirth
- 2) Fibrous connective tissue - has lots of blood and lymphatic vessels
- 3) Smooth muscle
- 4) Connective tissue - has rich network of blood vessels
Cul-de-sac
pouch that separates the posterior fornix and rectum
What happens to the vaginal wall during sexual arousal?
- vaginal wall becomes engorged with blood, which pushes som fluid to the surface of the mucosa enhancing lubrication
- vaginal wall doesn’t have mucus-secreting glands so secretions drain into the vagina from the endocervical glands or Bartholin/Skene glands
What two factors help with maintaining self-cleansing action of the vagina to defend from infection?
1) Acid-base balance - discourages proliferation of pathogenic bacteria
- before puberty: vaginal pH ~7
- at puberty: pH 4.0 - 5.0
2) Thickness of vaginal epithelium
- before puberty: thin epithelium
- at puberty: thickens
Protection is greatest during sexually active years and when estrogen levels are high and there is a normal population of Lactobacillus acidophilus. These changes are maintained until menopause (pH then rises again to alkaline levels and epithelium thins)
What is the structure of the uterus and how does it develop throughout puberty?
- hollow & pear shaped organ with its lower end opening into the vagina
- loosely held in position by ligaments, peritoneal tissue folds, and pressure of adjacent organs (bladder, sigmoid colon, rectum)
- In most women: uterus is tipped forward (anteverted) which makes it rest on the bladder but can exist in other positions
- Innervation: by motor and sensory fibers of ANS
- During puberty: attains its adult size and descends from abdomen to the lower pelvis (between bladder and rectum)
-
In a mature, non preggo female:
- 7-9 cm long, 6.5 cm wide with muscular walls 3.5cm thick
-
After preggo:
- enlarges ~1cm in all dimensions
What are the two major parts of the uterus?
1) Corpus: body of uterus
- Fundus: top of corpus (above where the fallopian tubes insert). Widest part of the uterus
- Isthmus: area just above the cervix. Narrowest part of the uterus
2) Cervix:“neck” of uterus - extends from isthmus to vagina
The endocervical canal is the passageway between upper opening (internal os) and lower opening (external os) of the cervix
What are the three layers that make up the uterine wall?
1) Perimetrium (parietal peritoneum) - outer serous membrane that covers uterus
2) Myometrium - thick muscular middle layer
3) Endometrium - aka uterine lining
- made of a functional layer (superficial compact layer and spongy middle layer) and basal layer
- Functional layer: responds to estrogen and progesterone; proliferates and sheds monthly between puberty and menopause
- Basal layer: attached to the myometrium and regenerates the functional layer after shedding (menstruation)
Which structure in the cervix does not have an endometrial layer?
What type(s) of cells are found here?
endocervical canal
lined with columnar epithelial cells which is continuous with the lining of the outer cervix & vagina (aquamous epithelial cells)
The point where the columnar and squamous epithelial cells meet is known as the ________________. What is this area particularly susceptible to?
transformation zone/squamous-columnar junction
vulnerable to HPV which can lead to cervical dysplasia or carcinoma. These are the cells that are removed for examination during a pap smear
Functions of the uterus
- anchors and protects a fertilized ovum, provides optimal environment while ovum develops, and pushes the fetus out at birth
- involved in sexual response and conception
- during sexual arousal, cervix dilates slightly while uterus increases in size and moves up and backward (like a tent) that results in the cervix sitting in semen
- during orgasm, rhythmic contractions facilitate sperm movement through cervical opening
Function of the cervix
- acts as a mechanical barrier to infectious microorganisms from the vagina
- external cervical os has a mucous plug (during luteal phase of menstrual cycle and pregnancy)
- During ovulation, mucus changes under estrogen influence and forms watery strands (spinnbarkeit mucus) that facilitates sperm transport into the uterus
- downward flow of cervical secretions also flushes microorganisms away from cervix and uterus
- pH of secretions are also inhospitable to bacteria, and there are enzyms and antibiotices (IgA) that are involved with immune system
Structure of fallopian tubes
Structure: aka oviducts/uterine tubes. Enter the uterus bilaterally just beneath the fundus. Curve up and over the two ovaries. Each tube ~8-12 cm long and 1 cm in diameter. At the ends, it is fringed (fimbriae) and called the infundibulum
Function: direct the ova from the spaces around the ovaries into the uterus (the fimbriae move and create a current that draws the ovum into the infundibulum and then into the fallopian tube. One in the tube, cilia and peristalsis push it towards the uterus
Where does fertilization occur? What happens when the egg is/is not fertilized?
- Fertilization occurs in the ampulla (distal third) of fallopian tube
- Sperm released into the vagina can travel upward through endocarical canal and uterine cavity to get to the fallopian tubes
- If an ovum is present in either tube, fertilization can happen
- ovum becomes a blastocyst and then implants itself in the endometrium of the uterine wall
- If not fertilized, ovum fragments and leaves uterus with menstrual fluids
Describe the structure and function of the ovaries.
Structure: primary female reproductive organs. Almond shaped and on both sides of the uterus. Suspended by mesovarium portions of the broad ligament, ovarian ligaments, and suspensory ligaments
- homologous to testes
- If at reproductive age: 3-5cm long, 2.5cm wide, 2cm thick, weighs 4-8 g
Function: secrete female sex hormones & development/release of female gametes
Describe the changes/process that occur during the ovarian cycle
- Follicular maturation, ovulation, corpus luteum development, corpus luteum degeneration
- At birth there are 1-2 mil ova within the primordial (immature) ovarian follicles
- By puberty, drops to 300k - 500k and some follicles and ova begin to mature (so there are follicles in different stages)
- Every menstrual cycle, one of the follicles that reaches maturation and releases its ovum (the remaining ones fail to develop or degenerate - these are atretic follicles)
- After ovum release, follicle develops into the corpus luteum
- if fertilization occurs, corpus luteum enlarges and secretes hormoens that maintain and support pregnancy
- if fertilization does not occur, it releases these hormones for 14 days and then degenerates which triggers the maturation of another follicle
- cycle occurs from puberty to menopause (except pregnancy or hormonal contraceptive use)
- At menopause: process stops and ovaries atrophy
Theca cells
granulosa cells
two types of cells in the ovarian follicle that secrete sex hormones
Theca cells: produce androgens that migrate to granulosa cells
Granulosa cells: convert androgens to estradiol
Female sex hormones include:
estrogen
androgens
progesterone
What is estrogen and what functions does it have?
generic term for 3 similar hormones derived from cholesterol: estradiol, estrone, estriol
Estradiol (E2) - most potent and plentiful. 95% of it produced by the ovaries (very little from the adrenal cortex and placenta)
Estrone: converted from androgen in ovarian and adipose tissue
Estriol: metabolite of estrone and E2
Functions:
- maturation of reproductive organs
- development of secondary sex characteristics, growth, and maintenance of pregnancy
- closure of long bones after growth spurt in puberty
- bone and skin maintenance
- systemic organ function
What are androgens and its function?
- primarily sex hormones produced in testes but occurs in small amounts (from adrenal cortex) in men and women, and from the ovaries
- some (dehydroepiandrosterone and androstenedione) are precursors of estrogens (estrone, estradiol)
Functions: skeletal growth & pubic/axillary hair growth during puberty. Activate sebaceous glands (acne). Involved in libido
What is progesterone and its function?
What is it: the 2nd major female sex hormone, sometimes known as the hormone of pregnancy. Secreted by the corpus luteum when stimulated by anterior pituitary (which is stimulated by LH).
Function: Works with estrogen to control ovarian menstrual cycle
- LH surges 24-36 hr before ovulation and promotes luteinization of granulosa in dominant follicle
- this results in progesterone production and the development of blood vessels and connective tissue
- thickens endometrium to prep it for implantation of blastocyte
Function/Effects during pregnancy:
- 1) maintaining thickened endometrium
- 2) relaxing smooth muscle in myometrium which prevents premature concentractions and helps uterus expand
- 3) thickening of myometrium to prepare for labour
- 4) promoting growth of lobules and alveoli in the breast to prep for lactation BUT preventing lactation until fetus is born
- 5) preventing additional maturation of ova by supressing FSH and LH (i.e. stops menstrual cycle)
- 6) providing immune modulation (tolerating against fetal antigens so that mom’s immune system does not attack fetus)
Menses (menstrual bleeding) starts with what and ends with what?
What factor(s) affect the onset of menses?
Starts with menarche (first menstruation)
Ends with menopause (cessation of menstrual flow for 1 year)
body weight (% of body fat may change metabolic rate and lead to hormone changes associated with early menarche - 11 years or younger)
How long do menstrual cycles last?
What factors affect menstrual cyclicity and regular ovulation?
- at first, cycles are anovulatory and vary between 10-60 days +
- regular patterns start once adolescence hits, cycles last 21-45 days
- through adulthood, most common the cycle length is 28 days (25-30 days)
- ~2-8 years before menopause, cycles begin to lengthen again
Factors:
- 1) activity of GnRH
- 2) initial pituitary secretion of FSH
- 3) estrogen (estradiol) positive feedback mechanism for FSH/LH surge prior to ovulation, oocyte maturation, corpus luteum formation, and progesterone production
Phases of the menstrual cycle
Two phases:
1) follicular/proliferative phase (postmenstrual)
2) luteal/secretory phase (premenstrual)
What happens during the follicular/proliferative phase of the menstrual cycle?
- occurs after menses (functional layer of endometrium sheds)
- Two simultaneous processes occur during this phase:
- 1) maturation of ovarian follicle
- 2) proliferation of endometrium
- GnRH and balanced activin & inhibin levels from granulosa cells contribute to increase in FSH levels from anterior pituitary - this stimulates follicles and rescues a dominant ovarian follicle from apoptosis (days 5-7 of cycle)
- Estrogen and FSH together increase # of FSH receptors in primary follicle which make them more sensitive to FSH. This also induces LH stimulation
- LH and FSH stimulation continue to encourage estrogen secretion and increased levels
- As estrogen levels increase, FSH levels drop due to increase in inhibit-B secreted by granulosa cells in the dominant follicle → this drop decreases the growth of less developed follicles
- estrogen causes endometrial cells to proliferate and stimulate LH production
- surge in FSH and LH is required for final follicular growth and ovulation
What marks the onset of the luteal/secretory phase?
What occurs during this phase?
Onset: ovulation (release of ovum from mature follicle)
What occurs during this phase:
- ovarian follicle begins to transform into corpus luteum
- LH is secreted from anterior pituitary which stimualtes corpus luteum to secrete progesterone which then initiates secretory phase of endometrial development
- Glands and blood vessels in the endometrium branch through the functional layer, glands secret a thin glycogen-containing fluid (which prepares for implantation because it’s full of nutrients)
- Human chorionic gonadotropin (hCG) is secreted 3 days after fertilization by blastocytes and maintains corpus luteum once implantation occurs (day 6 or 7)
- production of estrogen and progesterone will continue until placenta can adequarelt maintain hormonal production
- If no conception/implantation occurs, corpus luteum degenerates and stops its progesteron and estrogen production → this results in endometrium entering an ischemic/menstrual phase causing it to shed
How long do menstrual blood flows typically last? How much blood is lost?
What is menstrual discharge composed of?
- blood flow typically lasts 3-7 days (but can be irregular)
- blood loss can be 30-80ml with most of it being during the first 3 days of menses
- menstrual discharge consits of blood, mucus, and desquamated endometrial tissue, does not clot under normal circumstances
- usually dark and has musty odor on oxidation
What is the ovarian cycle and how is it regulated via hormones?
The process of follicular maturation, ovulation, corpus luteum development, and corpus luteum degeneration
- Decline in luteal phase estrogen, progesterone, and inhibin secretion allows FSH levels to rise (and slight LH increase)
- FSH stimulates granulosa cell growth and initates estrogen production
- A group of ovarian follicles then get recruited and begin to mature → eventually one becomes dominant and the others atrophy
- Dominant follicle begins to secrete progressively larger amounts of estrogen which increases pituitary sensitivity to GnRH (creating a +ve feedback look with FSH and LH surge)
- Ovulation occurs 1-2 hr before final progesterone surge or 12-36 hr after onset of FSH and LH surge
- Progesterone, proteolytic enzymes, and prostaglandins trigger mechanisms that control release of ovum
- FSH and LH surge also transform granulosa cells of follicle into corpus luteum, and corpus luteum secretes progesterone and estrogen
- progesterone acts to suppress new follicular growth during early/midluteal phases
- if pregnancy doesn’t occur, the corpus luteum persists 11-14 days and then regresses and disappears
What are the uterine phases of the menstrual cycle?
Follicular/proliferative phase, luteal/secretory phase, and menstruation
Midfollicular/proliferative phase: increased levels of estrogen contribute to endometrial repair and proliferation leading to endometrial thickness (luteal phase). Cervical mucus is thin and watery
Ovulation: peak estrogen occurs right before which maximally stimulates cervical glands to produce mucus (more abundant and elastic/spinnbarkeit). Tiny channels also develop which allow access for sperm into interior of uterus
Secretory phase: occurs after ovulation (where progesterone levels increase) and endometrial tissu develops secretory characteristics
Menstruation: Endometrial tissue breaks down when implantation does not take place (~11 days after oculation) and then shedding of tissue starts ~14 days after ovulation
What is the vaginal response to cyclic hormonal changes of the menstrual cycle?
- vaginal epithelial cells grow maximally during follicular/proliferative phase (influenced by estrogen)
- Cornification: keratinized cells overgrowing basal epithelium - occurs after ovulation
- Decornification: when leukocytes invade vaginal epithelium and remove the outer layers (near end of luteal phase)
How does body temperature change with menstrual cycle?
- Basal body temperature (BBT) has biphasic changes
- Follicular phase: BBT ~37C
- Luteal phase: BBT avg temp increases by 0.2 to 0.5 C
- Declines again to follicular phase levels at the end of luteal phase, 1-3 days before onset of menstruation
What are breasts and where are they located?
What is it: modified sebaceous glands
Location: ventral surface of thorax (superficial fascia of chest wall)
- extend vertically from 2nd rib to 6/7th ICS
- laterally from side of sternum to midaxillary line
- breast tissue may also extend into axilla (known as tail of Spence)
Describe the structure of the female breast
- composed of 15-20 pyramid-shaped lobes that are separated and supported by Cooper ligaments
- each lobe has 20-40 lobules (alveoli) that further subdivide into functional units (acini) → each acinus is lined with an epithelial layer that is capable of milk secretion and a subepithelial layer that is capable of contracting to squeeze milk from the acinus
- acini empty into a network of lobular collecting ducts which empty into interlobular collecting and ejecting ducts, and ducts reach the skin via openings/pores in the nipple
- lobes and lobules are surrounded and separated by muscle strands and fatty connective tissue
- Nipple: pigmented cylindric structure located at 4th-5th ICS with multiple openings on its surface; contains smooth muscles
- Areola: pigmented circular area around the nipple; contain smooth muscles
- Glands of Montgomery: sebaceous glands that are located within the areola and help with lubrication of the nipple during lactation
- Nipple becomes erect with sexual stimulation, breastfeeding, exposure to cold
Blood supply: internal and lateral thoracic arteries, intercostal arteries. Venous return empties into SVC. Lymphatic draining occurs through axillary nodes
Innervation: receives sensory info from 2nd - 6th intercostal nerves and cervical plexus
Describe the process of breast development throughout life stages
Childhood: latent growth. Only nipple and areola grow as body surface grows
Puberty: onset of puberty is breast development, stimulated by estrogen secretion.
Reproductive years: breast undergoes cyclic changes in response to changes in the levels of estrogen and progesterone assocaited with menstrual cycle
- estrogen promotes development of lobular ducts
- progesterone stimulates development of cells lining acini
- Increased prolactin levels after childbirth cause lactation and further prolactin secretion occurs with continued breast feeding
- Oxytocin also released after chilbirth and controls milk ejection from acini cells
What changes occur to the breast (structures) during follicular and luteal phases the menstrual cycle?
Follicular/proliferative phase: high estradiol levels increase vascularity of breast tissue and stimulate proliferation of ductal and acinar tissue. Progesterone levels icnrease and contribute to breast changes induced by estradiol
- progesterone also dilates the ducts and converts acinar cells into secretory cells
- leads to premenstrual breast fullness, tenderness, and increased breast nodularity
- breast volume may increase 10-30 ml
Luteal/secretory phase: effects are sustained into this phase
Function of female breast
- provide source of nourishment for the newborn
- Colostrum is produced in low quantities in first few days postpartum and is rich in immunologic components (IgA, lactoferrin, leukocytes, developmental factors)
Structure and development of the male breast
Development:
- up until puberty, development of male breast is similar to female breast
- however it doesn’t develop any further because of lower levels of estrogen and progesterone & antagonistic effects of androgens
Structure: mostly fat with small underdeveloped nipple and ductlike structures in subareolar area
External Male Genitalia
penis
testes
scrotum
epididymis
Structure of testes
Structure:
- oval and varies in dimensions and weight
- almost entirely surrounded by tunica vaginalis (outer covering made from vaginal processes during descent) which separates testis from scrotal wall and tunica albuginea
- inward extensions of tunica albuginea separate testis into ~250 compartments/lobules that have seminiferous tubules (where sperm production occurs)
- Tissues surrounding ^ are Leydig cells which occur in clusters and produce androgens
- two ends of each seminiferous tubule join and leave lobule via tubulus rectus leading to central portion of the testis (rete testis) - sperm move from efferent tubules (vasa efferentia) to epididymis where they mature
Innervation: adrenergic fibers (regulates blood flow to Leydig cells)
Blood supply: arterial blood from inernal spermatic and differentials arteries. Blood flows over testes surface and then enters parenchyma (functional tissues). Surface flow cools the blood to temperatures that promote spermatognesis (i.e. ~1-7C below body core temp). Testes are suspended outside pelvic cavity to facilitate cooling
Function and development of the testes
Function: 1) produce sperm (gametes); 2) produce sex hormones (androgens and testosterone)
Development:
-
Embryonic/fetal life: testes develop within the abdomen; descend towards developing scrotum ~3 months before birth.
- At ~1 month before birth, testes enter twin passageways (inguinal canals) which are vaginal processes created by peritoneal outpouchings
- processes close and inguinal canal disappears once descent is complete
Structure and Function of the Epipdidymis
Structure: comma-shaped structuer that curves over the posterior portion of each testis. Consists of a single, densely packed and coiled duct (5-7cm in length, 6m when uncoiled).
Functions: structurally, it conducts sperm from efferent tubules to the vas deferens. Physiologically, it functions to help with sperm maturation, mobility, and fertility.
- Sperm is immature when it enters head of epipdidymis so they are not fully motile or able to ferilize an ovum
- Takes 12+ days for sperm to travel the length of the epipdidymis where they can receive nutrients and testosterone
- After they travel the full length, sperm is stored in the epididymal tail and vas deferens (duct with muscular layers for peristalsis as it transports sperm towards urethra)
- vans deferens enters pelvic caivty through spermatic cord
Structure and Function of the Scrotum
Structure: skin-covered fibromuscular sac that is homologous to the labia majora. Covers the testes, epididymides, and spermatic cord.
- Skin is thin and has rugae which allows for enlarging or relaxing
- At puberty, skin darkens, develops active sebaceous glands, and becomes sparsely covered with hair
-
Tunica dartos: a layer of connective tissue that lies under the skin; also forms a septum that separates the two testes.
- Contracts in cold temperatures which pull testes close to warm body
- Relaxes in warm temperatures which suspend the testes away from body heat
Function: the contraction/relaxation of the tunica dartos helps regulate and promote optimal tempature for spermatogenesis. Scrotal sensitivity (to touch, pressure, temp, and pain) protects testes from potential harm
How does the scrotum change during sexual excitement?
- scrotal skin and tunica thcken, and the scrotum tightens and lifts
- spermatic cord shortens and partially elevates the testes towards the body
- as excitement plateaus, the engorged testes increase 50% in size, rotate anteriorly, and flatten against the body signaling impending ejaculation
Structure and Function of the Penis
Structure: homologous to the clitoris
- External: it is made up of a shaft with a tip (glans) that contains the urethral opening. Skin of the glans folds oer the tip of the penis which forms the prepuce/foreskin.
-
Internal: consists of urethra and 3 compartments/sinusoids (two corpora cavernosa, one corpus spongiosum) that are separated by Buck fascia
- compartments are enclosed by tunica albuginea
- urethra passes through the corpus spongiosum and ends at the sagittal slit in the glans
Function: 1) delivery of sperm to the female vagina AND 2) elimination of urine
Erectile reflex
- a process where erectile tissues within the corpora cavernosa and corpus spongiosum become engorged with blood (allows penetration of the female vagina)
- the arterioles that supply the vascular spaces in these erectile tissues are dilated and filled with blood causing expansion of the tissue and an erection
- Erection is maintained by compression or constriction of veins that drain the corpora cavernosa and corpus spongiosum
- veins open when sexual stimulation stops/ejaculation occurs and blood flows out of the arterioles. Penis becomes flaccid
When do erections and ejaculation begin (i.e. life stage)?
What changes occur with the penis during sexual excitment?
- Erections begin in utero and continue throughout life but ejaculation does not occur until sperm production begins at puberty
- Growth of penis and scrotal contents continue past puberty (not complete until teens/early twenties)
- Sexual excitement causes corpora cavernosa to increase in length and width, become rigid causing penis to become erect
- Stimulation of the glands provides max erotic sensation (because lots of nerve endings)
- With sexual arousal, skin color deepens, glans doubles in size, and urethral meatus dilates
- Ejaculation occurs with strong contractions of vas deferens, epididymis, seminal vesicles, prostate, urethra, and penis
Internal male genitalia consists of:
1) Ducts: consist of two vasa deferentia, ejaculatory duct, and urethra. Conducts sperm and glandular secretions from the testes to the urethral opening of the penis
2) Glands: consist of prostate gland, two seminal vesicles, and two Cowper (bulbourethral) glands. Secretes fluids that serve as a vehicle for sperm transport and create nutritious alkaline medium that promotes sperm motility and survival
Semen: sperm x glandular fluids
Describe the pathway in which sperm takes to be ejaculated.
1) Sperm leave epididymides and travel rapidly through internal ducts (emission - occurs moments before ejaculation when sex arousal peaks)
2) Emission occurs as smooth muscle in epididymides wall and vasa deferentia contract rhythmically (peristalsis) - this pushes sperm and secretions through the vasa deferentia
3) As sperm leaves ampulla (wide portion) of vas deferens, seminal vesicles secrete a nutritious glucose-rich fluid into the semen
4) semincal vesicles (glands behind the urinary bladder but in front of rectum) join the ampulla to become the ejaculatory duct which then joins the urethra where they both pass through the prostate gland
5) During emission and ejaculation, a sphincter closes which prevents urine from entering the urethra
Structure and function of the prostate gland
Structure: size of walnut, surrounds the urethra, made of glandular alveoli and ducts embedded in fibromuscular tissue
Function: when semen moves through the prostatic portion of the urethra, the prostate gland contracts rhyhtmically and secretes prostatic fluid (thin milky substance with an alkaline pH to help sperm survive in acidic environment in females). The secretions also help to mobilize sperm after ejaculation
Function bulbourethral glands (Cowper glands)
Function: last pair of glands to add fluid to the ejaculate. Ducts secrete mucus into the urethra near the base of the penis before semen is expeled via muscle constractions
Average ejaculate amount and composition
Avg: 2-6ml of semen (contains 75- 400 million sperm)
~98% of ejaculate consists of glandular fluids (60-70% from seminal vesicles and 20% from prostate)
Spermatogenesis takes place within what structure?
Describe the process of spermatogenesis
- Occurs within seminiferous tubules of testes
Process of sperm production: whole process takes ~70-80 days
- basement membrane of seminiferous tubules is lined with diploid (46 chromosome) germ cells (spermatogonia) that undergo mitotic division
- Some move away from basement membrane and mature to become primary spermatocytes
- ^ these can undergo meiosis (two haploids now) into secondary spermatocytes
- ^ these further undergo meiosis again into four spermatids which then differentiate into spermatozoa (sperm) each with 23 chromosomes
-
Sertoli cells (nondividing support cells): determine if spermatids develop into sperm
- spermatids attach themselves to Sertoli cells to receive nutrients and hormonal signals needed to develop into sperm
What are the male sex hormones and their function in males?
Androgens - Testosterone: primary male sex hormone/androgen - primarily produced by Leydig cells of testes (and some from adrenal gland)
Functions:
- sexual differentiation
- urogenital system development
- affects nervous and skeletal tissues, bone marrow, skin and hair, & sex organs
- anabolic effect on skeletal muscle tissue (which is why men and women have such different body weight and composition)
- stimulates growth of muscle and cartilage of larynx which causes voice deepening
- stimulates bone marrow and renal EPO production which causes increased Hb and Hct levels
- activates sebaceous glands = acne, coarse hair, facial hair
- associated with libido
What changes occur with aging with the female reproductive system?
Perimenopause: transitional period between reproductive and nonreproductive years (can last 1-8 years). Most will have variability in frequency and quality of menstrual flow 5-10 years prior too. Sx: shortening of menstrual cycle (shorter follicular phase, unpredictable ovulation) and then lengthening of cycle
Menopause: 12 consecutive months with no period. Due to loss of ovarian function, low estrogen and progesterone levels, and high FSH and LH levels. Within first 5 years is early menopause. Late menopause comes after up until death.
Ovarian changes: accelerated follicular loss which ends supply of follicles (increased FSH stimulation, decreased inhibin, slightly elevated estradiol levels
Uterine changes: 50% of perimenopausal women will have dysfunctional uterine bleeding (heavy, unpredictable) due to increased in anovulatory cycles that cause endometrium to thicken
Breast tissue changes: breast tissue becomes involuted, fat deposites and connective tissue increase. Breasts are reduced in size and firmness
Urogenital tract changes: ovaries shrink, uterus atrophys, vasgina shortens, narrows, and loses elasticity. Decreased lubrication and vaginal pH increases (higher risk of vaginitis). Cervix atrophies, cervical os shrinks, vaginal epithelium atrophies. Less pubic hair, less prominent labia major and minora. Urethral tone and pelvic muscle tone decline, leading to urinary frequency, urgency, UTIs, incontinence. Regular sex and organ may diminish some of these changes.
Skeletal changes: loss of bone mass leading to increased brittleness and porous bone. Possible osteoporosis esp in lumbar spine and femoral neck
Cardiac changes: Risk of CAD increases (increase in LDL, decrease in HDL)
Systemic changes: vasomotor flushes; changes in estrogen levels also can increase emotional stress (unpredictable mood swings), depression and anxiety, weight gian, migraine headaches, insomnia. Lower estrogen levels decrease skin thickness, diminish skin elasticity (more dryness and wrinkling)
What are vasomotor flushes?
- a rise in skin temperature, dilation of peripheral blood vessels, increased blood flow in the hands, increased skin conductance, and transient increase in HR followed by a temperature drop and profuse perspiration over flush areas
- face, neck, potentially chest and other areas
- Other Sx: dizziness, nausea, headaches, palpitations
- can vary in frequency, intensity, duration (1 - 15 years)
- Believed to be caused by rapid decreases in estrogen levels (estrogen replacement therapy may help with some symptoms)
What is the link between menopause and the risk of ovarian, breast, and uterine cancer?
- menopauses increases that risk
- risk is greater in those who start menstruating <12 y.o. or experiencing menopause after 55 y.o.
- women who menstruate longer than normal during a lifetime are exposed to more estrogen and have more ovulations (more estrogen exposure = more risk of uterine and breast cancers)
- More ovulations than normal increases risk of ovarian cancer
True or False. Men maintain reproductive capacity longer than women, and that there is no distinct even that characterizes aging of the male reproductive system
True
Andropause - What is it and what factors contribute to this process?
emotional and physical changes associated with androgen deficiency in the aging male (only occurs in a small % of men)
Contributing factors: decreased testosterone levels, change in responsiveness of target tissues, decreased levels of sex hormone binding globulin, changes in hypothalamus and pituitary gland
What changes occur with aging with the male reproductive system?
Sexual drive/Libido: influenced by changes in health status and testosterone levels (influenced by social, psych, and environmental factors)
Erectile/ejaculatory capacity: longer stimulation needed to achieve full erection, slower and less forceful ejaculation, less pelvic muscle involvement. Decreased vasocongestive response, longer refractory time (up to 24 hours)
Testicular changes: decreased weight, atrophy, softening of testes. Seminiferous tubules thicken in basement membrane area, arrest of germ cells, decrease in spermatogenic activity, and collapse. Sclerosis and fibrosis eventually cause complete obstruction. Decreased semen volume, sperm concentration, sperm motility and changes to morphology. Decreased fertility.
Hormonal changes: hormone synthesis decreases, target tissues decline in responsiveness. Decreased testosterone levels as Leydig cells decrease in number. Gonadotropin levels increase.
Associated changes: functional deterioration of accessory sex organs. Loss of muscle mass, strength, and endurance which contribute to decrease libido
A female with a suspected reproductive-related problem will likely complain of pain where?
pain from umbilicus to lower abdomen
LLQ to suprapubic region and RLQ
Androgen insensitivity syndrome (AIS)
Definition, Cause, Clinical Manifestations
Definition: hormone resistance disorder characterized by a female phenotype in someone who is XY and has testes producing age-appropriate androgen concentration
Cause: often genetic mutation to androgen receptor (AR)
Clinical Manifestations:
- Complete androgen insensitivity: testes palpable within labia majora, normal breast development but sparse axillary/pubic hair; no menarche because no uterus, cervix, and ovaries. Short vagina that ends blindly.
- Milder insensitivity: less dramatic phenotype manifestations, many have normal male genitalia
Genotype vs phenotye
Genotype: the genetic constitution of an individual organism (i.e. XY male genotype)
Phenotype: set of observable traits of an individual resulting from interaction of its genotype with the environment
What do uterine abnormalities typically stem from?
How are they diagnosed and what is the prognosis?
Origin: most stem from abnormal cell migration in the müllerian ducts during key moments in fetal development
Diagnosis: rarely diagnosed until women has trouble becoming pregnant or carrying a baby to term because the uterus is capable of menstruation but may have difficulty supporting a growing fetus. Dx done via ultrasound during pregnancy or MRI.
Prognosis: depends on severity of malformation and location and size of placenta and fetus. Some can be surgically corrected to improve outcome of future pregnancies
Potential abnormalities in lower genital tract
- two vaginas
- vaginal septum (thin membrane dividing the vaginal vault)
- for most, there are no functional problems but can be surgically corrected if needed
Normal range for onset of puberty is
8-13 years old - however age of onset is multifactorial and can be influenced by many things
Delayed/Absent Puberty
Definition: sexual maturation occuring later than usual, secondary sex characteristics are developed later
- 95% cases this is a normal physiologic event (normal hormone levels, HPG axis is intact, maturation is slowly occuring) - tx rarely needed UNLESS it’s psychosocial in nature
- 5% of cases are caused by disruption in HPG (hypothalamix-pituitary-gonadal) axis or systemic disease
Causes: trauma/infections causeing gonadal failure, genetic abnormalities, tumors, etc.
Precocious Puberty
Definition, Cause, Types, Treatment
Definition: sexual maturation <6 (in black girls), <7 (in white girls), and <9 in boys. Rare.
Causes: various - obesity, increased protein consumption, endocrine disruptiors (from common household products, pesticides, pharmaceuticals), lethal CNS tumors
Types:
- Complete precocious puberty: premature development of appropriate characteristics for the child’s gender (onset and progression of all pubertal features - thelarche, pubarche, menarche)
- Partial precocious puberty: partial development of appropriate 2’ sex characteristics
- Mixed precocious puberty: development of 2’ sex characteristics of the opposite gender (virilization of a girl, feminization of a boy)
Treatment: idnetifying underlying cause or administering appropriate hormones. Many are reversible
What are common signs and symptoms of reproductive-related disorders in females?
- Abdominal, pelvic pain - periumbilical (around umbilicus) or lower
- Abnormal vaginal drainage, hemorrhage - (amniotic fluid, blood, etc.)
- Burning/itching of genitals
- Urinary - frequency, incontinence, dysuria (burning? UTI symptoms)
- Breast changes, discharge from nipples - blood? breastfeeding?
- Trauma
Dysmenorrhea
Definition, Patho, Clinical Manifestations, Diagnosis, Treatment
Definition: painful or difficult menses
- Primary dysmenorrhea: painful menstruation associated with release of prostaglandins in ovulatory cycles but not wiht pelvic disease. Begins with onset of ovulatory cycles and highest prevalence during adolescence. 50% experience this, 10% are incapacitated for 1-3 days due to pain severity.
- Secondary dysmenorrhea: related to pelvic pathologic conditions, manifests later in reproductive years, and can occur any time in menstrual cycle
Pathophysiology: Primary dysmenorrhea due to excessive prostaglandin F2α which is a potent stimulant of myometrium and vasoconstrictor. Causes increased myometrial contractions, constricts endometrial blood vessels, and enhances nerve hypersensivity (pain). Can lead to ischemia and endometrial shedding. May be due to increased COX enzyme activity. First 48 hours of menstruation have higher prostaglandin levels.
Secondary dysmenorrhea: due to disorders like endometriosis (most common cause), endometritis (infection), pelvic inflammatory disease, adhesions, obstructive uterine or vaginal anomalies, inflammation, uterine fibroids, polyps, tumors, cysts, IUDs
Clinical Manifestations: *pelvic pain with onset of menses*. Severity related to length and amount of menstrual flow. Pain often radiates into groin. May also have backache, anorexia, vomiting, diarrhea, syncope, headache (due to prostaglandins and its metabolites entering systemic circulation). Usually starts right before period and rarely persists 1-3 days during menstrual flow.
Diagnosis: obtain history and pelvic exam to differentiate between 1’ and 2’.
Treatment: NSAIDs (to reduce COX enzyme activity). Hormonal contraceptives (stops ovulation and creates an atrophic endometrium which decreases prostaglandin synthesis and myometrial contractility)
- Regular exercise and stress reduction
- Palliative approaches: heat, acupuncture, TENS, supplements, herbal tx
Amenorrhea (Primary)
Definition, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Definition: lack of menstruation
- Primary amenorrhea: fialure of menarche and absence of menstruation by 13 y.o. without development of 2’ sex characteristics OR by 15 y.o. regardless of presence of 2’s sex characteristics
Causes: pregnancy; Other most common ones - hypothalamic dysfunction, PCOS, hyperprolactinemia, and ovarian failure
Pathophysiolpgy: compartmentalize the causes
- I—Anatomic defects (i.e. no uterus, vagina)
- II—Involve the ovary, genetic disorders (turner syndrome), and androgen insensitivity syndrome (AIS)
- III—Involve anterior pituitary gland and result in failure of hormonal signaling to ovaries (tumors that cause failure of signaling via FSH and LH)
- IV—CNS disorders, primarily hypothalamic defects the prevent secretion of GnRH
Clinical Manifestations: absence of first menstrual period. Cause of amenorrhea will determine whether 2’ sec characteristics and height are affected
Diagnosis: hx taking andphysical exam to determine presence/absence of 2’ sex characteristics. Lab studies to look at levels of gonadotropins or ovarian hormones. MRI.
Treatment: treat underlying cause and hormone replacement therapy to induce development of 2’ sex characteristics.
Secondary Amenorrhea
Definition, Causes, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Definition: Absence of menses (3 or more cycles) after previous menstrual periods
- common and normal during early adolescence, pregnancy, lactation, and perimenopausal period (primarily due to anovulation)
Common causes: (MOST COMMON is pregnancy) - others: thyroid disorders, hyperprolactinemia, HPO interruption 2’ to excessive exercise, stress, or weight loss, PCOS
Pathophysiology: depends on the cause. see screenshot.
Clinical Manifestations: absence of mesnses after previous menstrual periods. May also have infertility, vasomotor flushes, vaginal atrophy, acne. osteopenia, and hirsutism (abnormal hairiness) depending on the cause of amenorrhea
Diagnosis: must rule out pregnancy first. History (stress, extreme exercise, large dietary changes, eating disorders, sleep abnormalities) and physical exam. Rule out hypothyroidism. Identify hormone or anatomic alterations.
Treatment: Depends on cause - hormonal replacement therapy, corrective procedure (surgical removal of pituitary tumor).
What is the most common cause of abnormal uterine bleeding/cycle irregularity?
failure to ovulate related to age, stress, and endocrinopathy
Define the following abnormal menstrual bleeding patterns.
Polymenorrhea
Oligomenorrhea
Metrorrhagia
Hypermenorrhea
Menorrhea
Menorrhagia
Menometrorrhagia
Polymenorrhea: cycles shorter than 3 weeks. May indicate disturbance in endocrine control of ovulation
Oligomenorrhea: cycles longer than 6-7 weeks. May indicate disturbance in endocrine control of ovulation
Metrorrhagia: abnormal bleeding between periods; may be sign of organic disease
Hypermenorrhea: excessive flow, may be a sign of organic disease
Menorrhea/Menorrhagia: increased amount and duration of flow
Menometrorrhagia: prolonged flow associated with irregular and intermittent spotting between bleeding episodes
Dysfunctional Uterine Bleeding (DUB)
Definition, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Definition: heavy or irregular bleeding in the absence of organic disease. Affects perimenopausal women the most (they take up 50% of cases as a result of irregular ovulation)
Pathophysiology: primarily due to lack of ovulation. Failure to ovulate causes irregular menstrual bleeding due to lack of progesterone and sometimes excess estrogen. This results in excessive and irregular endometrial thickness and subsequent excessive and irregular bleeding.
- Contributing factors: PCOS, obesity, thyroid disease
- Other causes: corpus luteum defects resulting in progesterone deficiencies, abnormalities in uterus or cervix (endometrial polyps, fibroids, cancer)
Clinical Manifestations: unpredictable and variable amount and duration of bleeding. May lead to flooding and passing of large clots which leads to excessive blood loss. This can lead to iron deficiency anemia and related symptoms (fatigue, SOB).
Diagnosis: DUB diagnosed after other causes have been ruled out. If no cause found, usually assumed that bleeding is caused by a lack of regular ovulation.
Treatment: NSAIDs first line of tx for excessive menstrual beleeding because it reduces prostaglandin synthesis within endometrial tissues which leads to vasoconstriction and decreased bleeding. Most effective when taken few days before beginning of menstrual period and continued through days of heaviest bleeding.
- Goal is to control bleeding, prevent hyperplasia, prevent or treat anemia, and treat concurrent endocrine problems if present
- Oral contraceptives that have estrogen and progesterone
- levonorgestrel IUD (LNG-IUD)
- If no desire for future babies: ablation, hysterectomy
Polycystic Ovary Syndrome (PCOS)
Definition. Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Definition: hormonal disorder where ovaries produce abnormal amount of androgens. One of the most common endocrine disturbances affecting women, leading cause of infertility in US.
Diagnosis criteria: at least two of the following
- few or anovulatory menstrual cycles
- elevated levels of androgens
- polycystic ovaries
Pathophysiology: genetic predisposition and an obesity-prone lifestyle related to insulin resistance and excess insulin and androgens. Cardinal feature: hyperandrogenic state; this is exacerbated by glucose intolerance/insulin resistance and hyperinsulinemia and causes worse S/S. PCOS predisposes to obesity and pre-existing obesity predisposes to more severe PCOS.
- Insulin resistance causes compensatory hyperinsulinemia which overstimulates androgen secretion by ovarian stroma and reduces hepatic secretion of serum sex-hormone-binding globulin (SHBG)
- Net effect is increase in free testosterone levels
- Excessive androgen affects follicular growth and insulin suppresses apoptosis of follicles that typically disintegrate
Inappropriate gonadotropin secretion triggers a cycle that worsens anovulation. Elevated LH levels cause increased androgen levels from adrenal glands/ovaries that are then converted to estrogen and testosterone. This decreases SHBG which causes increased free estradiol levels. Elevated estrogen levels trigger a +ve feedback response in LH and a -ve feedback response in FSH. New follicular growth is continuously stimulated by not to full maturaiton and ovulation.
Clinical Manifestations: usually show up within 2 years of puberty. S/S related to anovulation and hyperandrogenism. DUB or amenorrhea, hirsutism, acne, infertility. HTN and DLD common
Diagnosis: based on evidence of excess androgen (hirsutism, male pattern hair distribution, acne), chronic anovulation, insulin resistance, inappropriate gonadotropin secretion (low [FSH], high [LH] and [DHEA])
Treatment: combination of oral contraceptives to controll irregular menstrual cycles and oppose estrogens and androgens. Metformin to decrease insulin resistance. Weight loss.
Premenstrual syndrome (PMS)/Premenstrual dysphoric disorder (PMDD)
Definition, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Definition: Condition with a combination of symptoms and cyclic physical, psychologic, or behavioral changes that impair interpersonal relationships or interfere with usual activities. Occurs in the luteal phase of the menstrual cycle. PMDD is a more severe sometimes disabling extension of PMS
Pathophsyiology: multiple theories - increased vulnerability to fluctuations in ovarian-derived hormones and HPA axis changes. Erratic ovarian hormone fluctuation may cause vasomotor symptoms (hot flashes) and perimenopausal depression. NTs (5HT, GABA, NE) may interact with estrogen/progesterone and cause mood/behavioura changes. Genetics and environmental factors also play a role - i.e. family predisposition.
Clinical Manifestations: symptoms begin after ovulation during luteal phase and persist up to 4 days into menstrual cycle. Pattern of symptom frequency and severity is more important than specific complaints. ~300 physical, emotional, and behavioural symptoms are attributed to PMS/PMDD. Emotional symptoms: depression, anger, irritability, fatigue - most prominent. Physical symptoms are least prominent.
Diagnosis: based on health history and symptoms.
Treatment: symptomatic treatment (stress reduction, exercise, counseling, biofeedback, diet, rest). Two major forms of treatment: hormonal cycle regulation & SSRIs
How do infections of the genital tract occur in females?
Exogenous: pathogens introduced via sexual transmission
Endogenous: from microorganisms that are normally there in the vagina, bowel, or vulva but then migrate to a new location or overproliferate when immune system/defence mechanisms are down
Pelvic Inflammatory Disease (PID)
Definition, Causes, Risk Factors, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Definition: acute inflammatory process caused by infection & can involve any organ(s) of the upper genital tract (uterus, fallopian tubes, ovaries).
- Most severe form - entire peritoneal cavity
Causes: most are sexually transmitted infections (mainly chlamydia & gonorrhea) that migrate from vagina to uterus, fallopian tubes, and ovaries. Microorganisms that make up vaginal flora. CMV. Spontaneous or induced abortions, normal/abnormal deliveries (puerperal infections), other surgeries.
Risk factors: infection by previous STD, multiple sex partners or a partner who has had multiple sex partners/previous PID, being sexually active 25 y.o. or younger, useing douches, IUD for birth control.
Pathophysiology: development of infections depends on virulence of microorganisms, size of population, immune defense of the pt. PID develops when pathologic microbes ascend from an infected cervix to infect the uterus and adnexae (uterine appendages). Initial infection involves endocervical mucosa, Bartholin gland, or others and then move upwards towards fallopian tubes and tubo-ovarian region.
- Anaerobic bacteria have also been involved with increasing PID risk due to their ability to alter pH of vaginal environment and decrease mucus integrity that’s blocking the cervical opening
- greatly associated (66% of cases) with bacterial vaginosis (BV)
Clinical Manifestations: varies - from sudden severe abdo pain with fever OR asymptomatic. First sign of ascending infection may be onset of low bilateral abdominal pain that is dull and steady with a gradual onset. Sx more likely to develop during or immediately after menstruation. Pain may worsen with walking, jumping, or sex. May also have dysuria and irregular bleeding.
Diagnosis: limited and vague symptoms. Likely diagnosis if a sexually active women has abdominal/pelvic tenderness and one of the following:
- cervical motion tenderness
- uterine tenderness
- adnexal (uterine appendages) tenderness
Treatment: broad spectrum antibiotics, pelvic rest (no intercost, physical rest, comfort measures). If uncorrected, can lead to sepsis, organ scarring, and infertility.
Salpingitis
Definition, Pathophysiology, Complications
Definition: inflammation of the fallopian tubes
Pathophysiology: inflammatory process develops after the infection has been established and causes changes in the columnar epithelia that line the upper reproductive tract. Inflammation causes localized edema and potential necrosis in that area.
- Gonorrhea gonococci: attach to the fallopian tubes and secrete a toxic substance to the tubal mucosa which causes further inflammation and damage
- Chlamydia: enters the tubal cells and replicates which bursts the cell membrane as it reproduces, resulting in permanent scarring
- Both^ can spread to the abdominal cavity via openings of the fallopian/uterine tubes
Complications: peritonitis & bacteremia - increases risk for endocarditis, meningitis, and infectious arthritis. Chronic consequences - infertility and tubal obstruction, ectopic pregnancy, pelvic pain of varying degrees, intestinal obstruction from adhesions between the bowel and pelvic organs
Vaginitis
Definition, Cause, Patho, Clinical Manifestations, Diagnosis, Treatment
Definition: irritation or inflammation of the vagina, typically caused by infection. Characterized by an increased in WBCs on saline wet prep exam
- Vaginosis: vaginal irritation without WBCs
Causes/Incidence: overgrowth of normal flora (such as with use of antibiotics which kill off normal vaginal flora and facilitate growth of Candida albicans), STDs, low etrogen levels during menopause (atropic vaginitis). Incidence - highest in women 15-24 y.o.
Pathophysiology: occurs with alterations in vaginal environment like changes to local defense mechanisms (skin integrity, immune reaction, vaginal pH). Changes in pH (from its normal 4-5.0) will increase risk of infection.
- Factors: douching; using soaps, spermicides, feminine hygiene sprays, deodorant menstrual pads/tampons; having conditions associated with increased glycogen content of vaginal secretions (pregnancy, diabetes)
Diagnosis: history, physical exam, examination of discharge (infection will show change in colour or copious amounts, bad odor, or irritating).
Treatment: development and maintaining acidic environment, relieving symptoms (pruritis, irritation), antimicrobial or antifungal meds to eradicate infectious organisms. Partner will also have to be treated if it can be sexually transmitted.
Cervicitis
Definition, Causes, Patho, S/S, Treatment
Definition: non-specific term describing inflammation of the cervix; defined by CDC as having two major diagnostic signs (either or both may be present)
- purulent or mucopurulent discharge from cervical os
- endocervical bleeding induced by gently introducing a cotton swab into the cervix
- Mucopurulent cervicitis (MPC): caused by 1+ sexually transmitted pathogens (Trichomonas, Neisseria, Chlamydia, Mycoplasma, Ureaplasma)
Causes: infectious or non-infectious causes - chemicals and substances introduced into vagina, disruptions to normal vaginal flora, STDs
Pathophysiology: infection causes cervix to become red and edematous. Mucopurulent (mucus and pus containing) exudate drains from external cercical os.
S/S: vague pelvic pain, bleeding, dysuria. Bleeding during sex or with pelvic exam, pap smears.
Treatment: treatment for PID while awaiting results of microbial testing (because mucopurulent cervicitis is a sx of PID). Treat women and sex partners: abstain from sex until therapy completed. Treat with antibiotics.
Vulvodyniavestibulitis (VV)
Definition, Classifications, Cause, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Definition: chronic vulvar pain lasting 3+ months without visible dermatosis; inflammation of vulva/vaginal vestibule or both; infection; neoplasia; or identifiable neurologic disorder. aka vulvitis, vestibulitis, or vulvovestibulitidynia
Classifications: based on location of pain, localized or generalized, whether pain is provoked, unprovokes, or mixed.
- Localized: characterized by pain from a cause that usually doesn’t cause pain (allodynia) to vulvar vestibule (entrance of vagina) area
- Generalized: diffuse pain pattern involving all of the pudendal nerve distribution and beyond
- Provoked: touch/stimulation elicits pain
- Unprovoked: pain that occurs in the absence of touch or stimulation
- Mixed: pain that varies with or without touch or stimulation
Cause: unidentified. Potentially multifactorial
Pathophysiology: proposed - chronic disorder of nerves supplying the vulva. Chronic irritants, recurrent infections, hormonal changes, and chronic skin conditions may trigger chronic inflammation. Normal sensations cause heightened sensitivity.
Clinical Manifestations: pain that can be burning, stinging, irritation, or raw.
Diagnosis: difficulty to evaluate and treat due to not well known mechanisms. Rule out/treating other conditions that may contribute to vulvar inflammation. Cotton swab testing to identify patinful areas.
Treatment: limited. Potentially lidocaine, topical antidepressants, botox. Bathing in lukewarm water in mild baking soda solution and ice packs. Avoid irritants, wear loose cotton clothin, use appropriate antimicrobial/antifungal treatments
Bartholinitis/Bartholin cyst
Definition, Causes, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Definition: acute inflammation of one or both of the ducts that lead from the introitus (vaginal opening) to the Bartholin/greater vestibular glands. Most lesions are cysts or abscesses.
- Chronic bartholinitis: presence of small cyst that is slightly tender but otherwise asymptomatic. Most don’t require tx and symptoms don’t occur unless there is an exacerbation of infection that causes an abscess to form in the gland itself
Causes: microorganisms that infect lower female reproductive tract (streptococi, staphylococci, sexually transmitted pathogens).
Pathophysiology: infection or trauma causes inflammatory changes that narrow the distal portion of the duct which leads to obstruction and stasis of glandular secretions. Obstruction can vary in size (1-8cm diameter) and be located in the posterolateral portion of the vulva.
Clinical Manifestations: red and painful affected area, pus at the opening of the duct. Possible fever, malaise.
Diagnosis: clinical manifestations and exudate culture to ID infectious microorganisms.
Treatment: broad-spectrum antibiotics. Pain relieved with analgesics and warm sitz baths. Surgical drainage for abscesses.
Pelvic Organ Prolapse (POP)
Definition, Causes, Risk Factors, Treatment
Definition: descent of one or more of the following: vaginal wall, uterus, or apex of vagina (after hysterectomy) - progressive descent of structures occur due to perineal muscles and endopelvic fascia losing tone and strength with aging which then fails to keep pelvic organs in proper positions.
- Uterine Prolapse: descent of cervix or entire uterus into the vaginal canal or completely through vagina and protrudes into introitus (severe), creating ulceration and discomfort
Causes: direct trauma (ex. childbirth), pelvic floor surgery, damage to pelvic innervation (esp. pudendal nerve).
Risk factors: in nulliparous women - occupational activities that require heacy lifting or chronic med conditions. Others: aging, obesity, hysterectomy, familial history.
Treatment: pessary - removable mechanical device that holds the uterus in position (first line of treatment)
- Kegal exercises: strengthens pelvic fascia
- estrogen therapy in menopausal women
- Last resort: surgical repair (with or without hysterectomy)
Degree of uterine prolapse
Grade 1: uterus is in upper half of vagina; not treated unless it causes discomfort
Grade 2: uterus near opening of vagina; some moderate symptoms
Grade 3: severe prolapse; cervix protrudes from vagina
Grade 2 and 3 cause feelings of heaviness, fullness, collapse through vagina.
What are cystoceles, rectoceles, and enteroceles?
Cystocele: descent of part of posterior bladder wall and trigone into the vaginal canal, usually caused by childbirth. Severe cases will have bladder and anterior vaginal wall bulge outside introitus.
- Sx: usually insignificant in mild-moderate cases; vaginal pressure if prolapse is large
- Increased bulging and descent of the anterior vaginal wall and urethra can be aggravated by vigorous activity, prolonged standing, sneezing, coughing, or straining; relieved by rest or recumbent/prone position
- Tx: management via vaginal pessary, Kegels, estrogen therapy for postmenopausal women, surgery last resort
Rectocele: bulging of rectum and posterior vaginal wall into the vaginal canal. Childbirth may increase damage and potentially lead to a rectocele. Sx may not appear until after menopause. May be produced or aggravated by lifelong chronic constipation and straining. Genetic and familial predisposition.
- Sx: vaginal pressure, rectal fullness, incompletel bowel evacuation
- Difficult defecation can be facilitated by applying manual pressure to the posterior vaginal wall
- Tx: management and prevention of constipation and possible use of pessary
Enterocele: herniation of rectouterine pouch into rectovaginal septum (between rectum and posterior vaginal wall). Can be congenital or acquired.
- Congenital: rarely causes symptoms or progresses in size
- Acquired: can result from muscular weakness caused by previous surgery or from pelvic relaxation disorders (uterine prolapse, cystocele, rectocele)
- Tx: surgical
Benign Ovarian Cysts
Incidence, Causes, Pathophysiology, Clinical Manifestations, Treatment
Incidence/Prevalence: can occur during anytime but most common reproductive years and at the extremes of the reproductive years. Increases when hormonal imbalances are more common (puberty, menopause). Benign ovarian cysts are quite common, comprises 1/3 of gynec. hospital admissions
Causes: most common - follicular cysts and corpus luteum cysts (aka functional cysts)
Pathophysiology: follicular and corpus luteum cysts are unilateral, typically 5-6cm in diameter. Occurs when follicle(s) are stimualted but no dominant follicle develops and completes maturation process. Types:
-
Follicular cysts: fluid-filled and can be caused by a transient condition where the dominant follicle fails to rupture or one or more of the nondominant follicles fails to regress.
- May be due to no progesterone production which causes GnRH release to increase FSH levels. This continues to stimulate follicles to mature, granulosa cells to grow, and estradiol levels to icnrease. This stimualtes follicular cysts to develop
- Sx: possibly asymptomatic, some pelvic pain, bloated, tender breasts, heavy/irregular menses
- Usually go away one regular cycle and progesterone levels are restored
-
Corpus Luteum cyst: Highly vascularized cyst formed by the granulosa cells left behind after ovulation. If large, can rupture and cause hemorrhage
- Spontaneously regresses with normal menstrual cycle
- S/S: dull pelvic pain and amenorrhea or delayed menstruation followed by irregular or heavier bleeding. If ruptured, massive bleeding and ++pain & immediate surgery is required
- Tx: oral contraceptives to prevent cyst formation
- Dermoid cysts: ovarian teratomas (contains elements of of all 3 germ layers). Usually asymptomatic but have malignant potential and should be removed.
Clinical Manifestations: most are asymptomatic. Cysts can cause ovarian torsion (rare) if large enough - ovaries will twist on its own ligaments which decreases blood supply to the ovary and cause extreme pain, usually as acute severe unilateral abdominal or pelvic pain.
Treatment: surgery for ovarian torsion
What are ovarian cysts? How do physiological cysts differe from neoplastic cysts?
Cyst: fluid filled sac or pocket on/near ovary (not a collection of cells - that’s a tumor)
- Physiologic: occurs from normal functioning ovary, resolves spontaneously if small with slight abdominal pain
- Neoplastic: abnormal, not relatede to function of ovary, found on ultrasound
Endometrial Polyps
Definition, Risk Factors, Clinical Manifestations, Diagnosis, Treatment
Definition: a benign mass of endometrial tissue and contains varied amount of glands, stroma, blood vessels. Usually solitary and can occur anywhere within uterus
- Polyps have varied structure and classified as hyperplastic, atrophic (inactive) or functionl
- Most often in those 40-50 y.o. but can occur at all ages
Risk factors: hyperestrogenic states, obesity, tamoxifen use, HTN
Clinical Manifestations: most are asymptomatic but can cause intermenstrual bleeding or excessive menstrual beleding.
Diagnosis: hysteroscopy, ultrasonography
Treatment: surgical removal
Leiomyomas
Definition, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Definition: aka myomas/uterine fibroids. Benign tumors that develop from smooth muscle cells in myometrium.
- Most common benign tumors of the uterus (many are small and asymptomatic)
- Estrogen- and progesterone-sensitive
- Risk factors: hereditary, nulliparity, obesity, PCOS, diabetes, black race, HTN
Pathophysiology: most leiomyomes occur in multiples in the fundus. Classified as subserous, submucous, or intramural
Clinical Manifestations: abnormal vaginal bleeding, pain, Sx related to pressure on nearby structures. Fibroids may contribute to infertility and obstruction during birth if large enough. Leiomyoma can make uterine cavity large which increases endometrial SA which causes increased menstrual bleeding.Fibroid is relatively slow growing so it allows adjacent structures to adapt to pressure which causes symptoms of abdominal pressure to develop slowly. Abdominal or genital heavieness with larger ones.
- pressure on bladder may contribute to urinary frequeny, urgency, and dysuria
- pressure on the ureter may cause distension upstream from pressure point
- rectosigmoid pressure may lead to constipation
Diagnosis: bimanual examination that reveals irregular nontender nodularity of uterus. Pelvic sonography and MI
Treatment: depends on symptoms, tumor size, age, reproductive status and overall health of person
- Most are asymptomatic so can be managed via observation
- Medical tx here is aimed at shrinking myoma or reducing symptoms (ex. hormone contraceptives)
- Myomectomy/removal of fibroid from uterine muscle (standard of care) may be less invasive than full hysterectomy
Adenomyosis
Definition, Clinical Manifestations, Diagnosis, Treatment
Definition: presence of islands of endometrial glands surrounded by benign endometrial stroma within uterine myometrium. Common in late reproductive years (high in 40 y.o. and those who take tamoxifen), & those who have given bith.
Clinical Manifestations: may be asymptomatic or may be assocaited with abnormal menstrual bleeding, anemia, dysmenorrhea, uterine enlargement, and uterine tenderness during menstruation. Secondary dysmenorrhea becomes increasingly severe as disease progresses.
Diagnosis: exam will show enlarged and globular uterus, most tender just before or after menstruation. Dx confirmed with ultrasonography or MRI
Treatment: symptomatic tx (NSAIDs, hormonal contraceptives, levonorgestrel IUD. Surgical resection or hysterectomy if severe.
Endometriosis
Definition, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Definition: presence of functioning endometrial tissue of implants OUTSIDE the uterus. This tissue still responds to hormonal fluctuations of the menstrual cycle.
Potential/theories of causes:
- retrograde menstruation - Endometrial tissue may flow retrograde into abdominopelvic cavity during menses and implants. Dries up and then creates an adhesion
- coelomic metaplasia (tissue replaced with another tissue - peritoneum, müllerian ducts, and germinal epithelium of the ovary all derived from coelomic wall epithelium)
- embryonic cell rest (embryonic cells that are at rest become activated)
- iatrogenic mechanical transplantation
- lymphatic and vascular dissemination
- genetic predisposition
Pathophysiology: Poorly understood - influenced by genetic, epigenetic, environmental, and cellular factors. Endometrial tissue is a highly dynamic tissue with regenerative tissue undergoing cyclic processes of growth, differentiation, shedding, and regeneration as part of the menstrual cycle. These depend on steroid hormones, growth factors, and leukocytes that affect the balance between proliferation and apoptosis.
- Endometriosis is considered benign but some (1%) will have increased risk of malignant transformation involving multiple pathways of development
- Defining feature: presence and proliferation of endometrial-like tissue (implants) (stromal and glandular tissue) in areas outside of uterine cavity (primarily in ovaries, fallopian tubes, bladder, rectosigmoid colon, and uterine myometrium) which then causes infertility and pain
Several characteristics in pathophysiology:
- (1) high levels of estrogen production are observed in endometriosis, with production of aromatase
- (2) evidence of switching of cell fates during development, where epithelial and mesenchymal transition (mesenchymal to epithelial and vice versa)
- (3) Inflammation and peritoneal leukocytes may facilitate progression of lesions in endometriosis
- (4) some components of innate immune system are involved in endometriosis (dendritic cells, macrophages, Toll-like receptors) and adaptive immune system (T- and B-cell functions) which can promote apoptosis, tissue damage, and multiorgan involvement
- (5) Development of lesions is dependent on new blood vessel development (angiogenesis)
- (6) Genetic and epigenetic roles present in endometriotic lesions and some ovarian cancers
- (7) Stem cells may contribute to endometriotic lesions
Cyclic changes depend on the blood supply of the lesions (implants) and the presence of glandular and stromal cells. Given sufficient blood supply, ectopic endometrium proliferates, breaks down, and bleeds with the normal menstrual cycle. Bleeding can cause inflammation which triggers inflammatory mediators and lead to fibrosis, scarring, adhesions, and pain.
Clinical Manifestations: varies in frequency and severity, can mimic other pelvic disease. Highly associated with infertility. Abdo/pelvic pain, dyschezia (pain on defecation), dyspareunia (pain on intercourse), and less commonly constipation and abnormal vaginal bleeding.
- If implants are within the pelvis: aymptomatic pevlic mass having irregular movable nodule and a fixed retroverted uterus on examination
- Most sx can be explained by proliferation, breakdown, and bleeding of ectopic endometrial tissue with subsequent formation of adhesions
- Dyschezia is hallmark sx and occurs when there os endometrial tissue implanting in rectosigmoid musculature and subsequent fibrosis
Diagnosis: symptoms, pelvic laparoscopy for definitive diagnosis. Classified as stages I (minimal), II (mild), and III (moderate).
Treatment: based on preventing progression of disease, alleviating pain, and restoring fertility. Conservative surgical treament - laparoscopic removal or endometrial implants.
What is unique about the female reproductive system that allows for tumors to grow without detection?
Can reproductive cancers or cervical cancers detected early?
malignant tumors are common. The pelvis and abdomen are poorly innervated and designed to accommodate a growing fetus so cancers in the reproductive tract can often grow large before causing pain
Reproductive cancers - likely dx early if there are sx such as vag bleeding
Cervical cancer - minimal symptoms until late in the process but can be detected early wih Pap smears
Cervical Cancer
Incidence/Prevalence, Causes, Risk Factors, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Incidence/Prevalence: 4th more common cancer in women worldwide. 4th highest death rate among cancers in women. Rates have declined significantly in US mainly due to prevalence and frequency of screening with the Pap test.
Causes: Almost always associated with HPV infection. High-risk (oncogenic) types of HPV (esp. 16 and 18) can cause high-grade dysplasia and cancer
- Precancerous lesions/dysplasia: Cervical intraepithelial neoplasia (CIN) and cervical carcinoma in situ (CIS)
- Process can be slow and invasive cancer can develop over 10-12 years
Risk factors: multiple sex partners, male partner with multiple previous/current sexual partners, young age at first sexual intercourse, high parity, persistent infection with HPV-16 or -18, immunosuppression, use of oral contraceptives, certain HLA subtypes, nicotine use.
Pathophysiology: Cervix is lined by two types of epithelial cells - squamous cells (outer aspect) and columnar glandular cells (along inner canal). HPV infects immature basal cells in areas of epithelial breaks/injury or immature cells at the transformation zone/squamocolumnar junction. Ability of HPV to act as a carcinogen depends on viral proteins E6 and E7 as they interfere with activity of tumor-supressing proteins that regulate cell growth and survival. HPV causing cancer also depends on immune/hormonal responses and other environmental factors that determine the persistence of HPV infection.
Slow progressive disease, moves from normal cervical epithelial cells to dysplasia to carcinoma in situ, and then cancer.
Clinical Manifestations: predominantly asymptomatic so 90% of them can be detected early via Pap and HPV testing. If Sx exist, it may be change in vaginal discharge or bleeding. Bleeding may vary and occur after intercourse or between periods. Complaints of abnormal menses or postmenopausal bleeding. Yellow vaginal discharge (less common). Odor. It advanced, then urinary or rectal symptoms and pelvic or back pain.
Diagnosis: Pap smears and HPV testing. If dysplasia detected, colposcopy to ID lesions and obtain needed biopsies.
Treatment: depends on degree of neoplastic change, size, location, extend of spread. Surgery, radiation therapy, chemo, targeted treatment. Excellent prognosis with early detection and treatment. PRevention of HPV infection via vaccines.
Vaginal Cancer
Incidence, Risk Factors, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Incidence: rarest of the female genital cancers. Can occur at any age but predominany in women 50+ y.o. and >90% have SCC.
Risk Factors: age 60+, diethylstilbestrol (DES) exposure in utero, HPV-16, HIV, genital warts,
Pathophysiology: Most SCCs of the vagina are associated with high-risk HPVs
Clinical Manifestations: can be asymptomatic. Abnormal vaginal bleeding discharge not releted to menstrual periods, pain during intercourse, pain in pelvic area, pain when urinating, and constipation.
Diagnosis: regular pelvic exams esp in women with a history of intrauerine DES exposure. Biopsy.
Treatment: depends on findings and pt age. Surgery, chemo, radiation therapy.
Vulvar Cancer
Definition, Risk Factors Pathophysiology, Diagnosis, Treatment
Definition: most often affecting labia majora, less often labia minora, clitoris, vaginal glands
Risk factors: HPV-16 (cause), HIV, HPV-18 (probable cause), aging, previous cancer, cervical cancer survivor, previous CIN, women with certain autoimmune conditions, immunosuppression, organ transplant recipients, tobacco use. Many sexual partners, first sexual intercourse at a young age, and history of abnormal pap tests. Any risk factors for STIs.
Pathophysiology: Majority are SCC. Development of vulvar cancer is preceded by condyloma or squamous dysplasia.
Dx/Tx: early detection is critical. Treatment includes surgery, radiationa, chemo, biologic therapy
Endometrial Cancer
Definition, Incidence/Risk Factors, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Definition: most common type of uterine cancer and gynecologic malignancy, 6th most common cancer worldwide. Classified into Type I and II. Type I ~80% of cases,
Incidence/Risk Factors: highest in high income countries. Primary risk factor is unopposed estrogen exposure (without progesterone). Others factors: chronic hyperinsulinemia, hyperglycemia, body fatness, adult weight gain, chronic inflammation, lack of physical activity.
- Associated with T2DM
- most occur in postmenopausal women, peak incidence in late 50s early 60s
Pathophysiology: Endometrial hyperplasia associated with estrogenic stimulation of estrogen. Alterations in endometrial cancer:
- 1) altered estrogen receptor (ER) and progesterone receptor (PR) expression
- 2) genetic mutation causing loss of function of tumor-suppressor gene PTEN
- 3) pveractive PI3K/AKT signaling pathway which increases ability of the estrogen receptor to turn on the expression of target genes
- 4) gene mutation
Progesterone inhibits estrogen-driven growth in uterus so if there is atypical expression of the PR that it may be anti- or pro-proliferative of endometrium
Clinical Manifestations: **abnormal vaginal bleeding** most common. More advanced stages: pain and weight loss.
Diagnosis: should be evaluated in postmenopausal, obese, or those with unopposed estrogen conditions (anovulatory cycles) if they have unscheduled or persistent, irregular vaginal bleeding. Biopsy if endometrial tissue is v thick.
Treatment: based on extent of disease - curettage for carcinoma in situ, hysterectomy, chemo, radiation
Ovarian Cancer
Incidence/Prevalence, Risk factors, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Incidence/Prevalance: leading cause of mortality in gynecologic malignancies (more deaths than all other gyne malignancies combined). highest incidences in more developed regions.
Risk factors: advancing age, fenetics, family history, BMI (obesity), height, reproductive/hormonal factors, menopausal hormone therapy, endometriosis, diabetes, previous cancer, smoking, asbestos, talc-based powder, ionizing radiation
- Risk is reduced by factors that suppress ovulation (pregnancy, breastfeeding, combined hormonal contraceptive use)
Pathophysiology: tumours arising from 3 ovarian components
- (1) from fimbriae of fallopian tubes and from deposits of endometriosis
- (2) from germ cells - pluripotent and migrate to the ovary from the yolk sac
- (3) from stromal cells
Normal ovary contains 3 major cell types that benign and malignant tumours come from:
- (1) germ cells that are derived from endoderm and migrate to gonadal ridge where they proliferate and differentiate into oocyte
- (2) endocrine and interstitial hormone producing cells that produce estrogen and progesterone
- (3) epithelial cells derived from müllerian ducts that cover ovary (most common of the malignant ovarian tumors - 90%)
Three major types of epithelial tumors: serous, mucinous, endometrioid. These all have benign, borderline, and malignant category
Clinical Manifestations: no early symptoms, disease is usually advanced by time treatment is sought. Possible vague symptoms: abdominal distention, loss of appetite, early satiety, pelvic pain. Advanced disease: pain, abdominal swelling/distention, dyspepsia (upset stomach), vomiting, alterations in bowel habits. Abnormal vaginal bleeding in postmenopausal endometrium. Pelvic pressure, leg pain.
- Tumour obstruction of vascular channels can cause thrombosis, coagulation, and metastasis can cause pleurla effusion
Diagnosis: difficult to diagnose early and treat. Routine screening. Biopsy.
Treatment: surgery (done to determine stage of disease and remove as much as tumour as possible). Treatment then customized based on cancer stage, woman’s desires, cell type, sensitivity of cancer cells. Radiation, chemo.
Sexual Dysfunction
lack of satisfaction with sexual function resulting from pain or deficiency in sexual desire, arousal, or orgasm
organic and psychosocial disorders that play a role
The most common sexual dysfunction in women is ______________.
What factors may affect this and what treatment would be suitable for this dysfunction?
disorders or desire (hypoactive sex desire, decreased libido)
Factors: aging, biological manifestation of depression, not being satisfied with relationships, hx of abuse, alcohol/substance use, prolactin-secreting pituitary tumors, testosterone deficiency, medications
Treatment: counseling, psychotherapy, antidepressants
What is anorgasmia (orgasmic dysfunction)?
What factors may contribute to this?
inability for a woman to orgasm (ranges from difficulty in arousal to lack of orgasm)
Factors: chronic illness affecting arousal, conditions that block orgasms like diabetes, alcoholism, neuro disturbances, hormonal deficiencies, and pelvic disorders. Meds (narcotics, tranquilizers, antidepressants, HTN meds)
Dyspareunia
What is it, potential causes
Definition: painful intercourse. Common. Pain may be burning, sharp, searing, cramping & can be external, vaginal, deep abdominal, or pelvic.
Causes: psychosocial and organic causes
- inadequate lubrication
- drugs with drying effect (ex. antihistamines, certain tranquilizers, marijuana)
- disorder (diabetes, vaginal infections, estrogen deficiency)
- Skin problems around introitus/vulva
- Irritation/infection of clitoris
- Disorders of vaginal opening, urethra, anus
- Pelvic disorders (infections, tumours, abnormalities to uterus/cervix
Vaginismus
Definition, cause
Definition: involuntary muscle spasm in response to attempted penetration
Causes: psychological - prior sex trauma, fear of sex. Organic - similar to dyspareunia including vulvovestibulitis
Infertility
Definition, Causes, Diagnosis, Treatment
Definition: inability to conceive >1 year of unprotected sex
Causes: Female infertility results from dysfunction of the normal reproductive process
- Menses and ovulation
- Fallopian tube function (egg transport, fertilization site)
- Implantation of fertilized egg
Ovarian dysfunciton: due to hormonal effects (PCOS, stress), diminished ovarian reserve (lacking eggs), premature ovarian insufficiency (failure of ovarian function <40 y.o.).
Fallopian tube dysfunction: from acute pelvic infections (chlamydia, gonorrhea)
Diagnosis/Evaluation: Initial workup includes semen analysis, determination of ovulation, and hysterosalpingography of the fallopian tubes
Treatment: correcting underlying cause. Male infertility corrected surgically or by artificial insemination from husband/donor sperm. For females, hormone medications to induce ovulation, assisted reproductive technology (IVF)
Galactorrhea
Definition, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Definition: inappropriate lactation; persistent and excessive secretion of milky fluid from breasts of woman who is not pregnant or nursing. Can also occur in men. Not associated with breast cancer.
Pathophysiology: not a primary breast disorder but rather occurs due to other pathological processes occuring somewhere else in the body. Chiefly hormonne imbalances caused by hypothalamus-pituitary disturbances, tumors, or neurological damage. Exogenous causes: drugs, estrogen, nipple manipulation.
Most common cause: nonpuerperal hyperprolactinemia - excessive amounts of prolactin in the blood that’s unrelated to preganancy or childbirth. Can be caused by anything that stimulates/overstimulates units that secrete prolactin in pituitary gland, anything that interferes with production of PIF (i.e. dopamine), anything that interferes with pituitary receptors for PIF
- Associated with certain drugs, hypothyroidism (which stimulates TSH and prolactin release from pituitary), and pituitary tumors (prolactinoma
- Chronic stress inhibits PIF
- head trauma, SCI, brain injuries can stimulate suckling reflex which increases prolactin secretion
Clinical Manifestations: milky breast secretion of nonpregnant, nonlactating women. Most also have menstrual abnomalities. If pituitary process involved, pt may also have hirsutism and infertility. If hypothalamic lesion: CNS symptoms (headhache, vision issues, sleep disturbances, abnormal temp, thirst, appetite)
Diagnosis: high serum prolactin levels. T4 and TSH levels measured to rule our hypothyroidism. MRI for locating adenomas
Treatment: ID and treating cause. Medical therapy is common, rare need for surgery or radiation therapy
Benign Breast Disease (BBD)
Definition, common sx, classifications
- Spectrum of noncancerous changes in the breast
- Most common sx: pain, palpable mass, nipple discharge
- Broadly classified
- Nonproliferative breast lesions
- Proliferative breast disease without atypia
- Atypical (atypia) hyperplasia
Benign Breast Disease (BBD) - Nonproliferative Breast Lesions
Definition, Pathophysiology
Definition: breast lesions not associated with increased risk of breast cancer. Lesions include:
- (1) simple breast cysts
- (2) papillary apocrine change - increase in ductal epithelial cells that has apocrine changes or eosinophilic cytoplasm
- (3) mild hyperplasia of the usual type - increase in # of epithelial cells within a duct that is more than 2 cells (but not more than 4) in depth
Pathophysiology: simple cysts are the most common and commonly occurs in those in their 30s to 50s. Feels “squishy” when they’re close ot the breast surface but if deeply embeeded then they can feel hard. Often rupture with release of secretory material into the adjacent tissue resulting in chronic inflammation and scarring fibrosis which contributes tot he firmness palpated.
BBD - Proliferative Breast Lesions wihtout Atypia
Definition: disorders characterized by proliferation of ductal epithelium or stroma (or both) without cellualr signs of abnormality (i.e. atypia). Types:
1) Usual ductal hyperplasia (UDH): additional epithelial cells that fill and distend the ducts and lobules (usually found by accident). Cells vary in shape and size but retain features of benign cells. No additional tx needed.
2) Intraductal papillomas: Solitary or diffuse papillomas. Solitary ones have same array of cells that grow from the cyst wall into lumen of duct. Growth can occur when dilated duct near nipple causes benign nipple dischare. Diffuse papillomatosis: multiple papillomas and may be present as masses or cause nipple discharge. Lesions require surgical excision.
3) Sclerosing adenosis: lobular lesion with increased fibrous tissue and scattered glandular cells.
4) Radial scar (RS): irregular, radial proliferation of ductlike small tubules entrapped in a dense central fibrosis. Usually discovered when a breast lesion/abnormality is biopsied and removed.
5) Simple fibroadenomas: benign solid tumors that have glandular and fibrous lesions. Uknown etiology but potentially due to hormonal issues. Usually regress after menopause.
BDD - Proliferative Breast Lesions with Atypia
Definition, Risk/Incidence, Diagnosis/Treatment
Atypical Hyperplasia (AH): increase in number of cells with cells having variation in structure (atypia). High risk benign lesion
- Atypical ductal hyperplasia (ADH): abnormal proliferation of cells in breast ducts
- Atypical lobular hyperplasia (ALH): proliferation of cells in lumen of lobular units
Risk/Incidence: Those with AH have increased risk of breast cancer compared to nonproliferative lesion. The younger a woman is when diagnosed with atypical hyperplasia, the higher the risk that breast cancer will develop
Diagnosis/Treatment: physical exam, mammography, ultrasonography, MI, biopsy. Treatment is symptom relief (i.e. reducing caffein intake and chocolate to reduce overstimnulation and pain and nodularity in some women).
The most common cause of cancer death among women, and the leading cause of death in women 40-44 y.o. is ______________.
Breast cancer
What factors/risks contribute to the development of breast cancer?
- risk is related to timing, duration, and pattern of exposures
- Risk factors can be classified as: reproductive, hormone, environmental and familial
- Two other important factors:
- Involution of mammary gland
- breast density
Reproductive factors that contribute to breast cancer
- Reduced risk if first pregnancy at young age
- Pregnancy-associated breast cancer (PABC): Breast cancers that occur during pregnancy, and risk may persist to at least 5 years postpartum and longer
- Hypothesis: breast cancer risk is due to gland involution after pregnancy and lactation uses some of the same tissue remodeling pathways activated during wound healing (proinflammatory pathways) which promotes tumour progression
Describe how lobular involution, age, and postlactational involution contribute to breast cancer
-
Terminal duct lobular units (TDLUs): structures of the breast that are responsible for lactation - The predominant source of breast cancers
- Aging causes breast lobules to involute/regress with decrease in size and number of acini per lobule and replaced with intralobular stroma (denser collagen of tissue)
-
Lobular involution - glandular elements and collagen in lobules replaced with fatty tissue. Associated with reduced risk of breast cancer
- Wound healing process occurs during involution which results in a proinflammatory states that can promote carcinogenesis - transient increased in breast cancer risk followed by long term risk reduction)
- Postlactational involution - Mammary gland regresses and remodels to its prepregnant state (fibroblasts involved with secrete proteases that degrade ECM proteins and release bioactive matrix fragments that promote tumor growth)
- Oophorectomy: removal of ovaries - decreased risk in breast cancer possibly due to accelerated involution
Hormonal factors that contribute to risk of breast cancer
Six factors that affect risk of breast cancer:
- 1) Protective effect of an early (i.e., in the 20s) first pregnancy
- 2) Protective effect of removal of the ovaries and pituitary gland
- 3) Increased risk associated with early menarche, late menopause, and nulliparity
- 4) Relationship between types of fat, free estrogen levels, and oxidative changes in estrogen metabolism
- 5) Hormone-dependent development and differentiation of mammary gland structures
- 6) Efficacy of antihormone therapies for treatment and prevention of breast cancer
Vast majority of breast cancers are initially hormone dependent. Estrogen plays prominent role in cellular proliferation, differentiation, and apoptosis. Androgen receptor (AR) has been implicated in prostate cancer and development/progression of breast cancer.
Four major hormonal hypotheses for breast cancer:
- 1) ovarian androgen excess (ex. testosterone) - due to chronic anovulation and progesterone deficiency
- 2) estrogen and progesterone levels - increased proliferation rates of breast epithelium when these hormones were also produced by ovaries. Increases postmenopausal breast cancer risk
- 3) elevated estrogen levels alone - elevated levels and breast cancer risk
- 4) local (paracrine) biosynthesis of estrogens in breast tissue
Describe hormone replacement therapy and breast cancer risk
- Estrogen plus Progesterone Therapy (MHT)
- Estrogen Only Therapy (ET)
Estrogen-progestogen menopausal therapy and estrogen-progestrogen contraceptives are carcinogenic agents for breast cancer
Insulin and Insulin-like Growth Factors (IGFs) and their role in breast cancer risk
- IGFs regulate cellular functions involving cell proliferation, migratory, differentiation, and apoptosis
- Diabetes (and insulin resistance, increased insulin level, estrogen and GH levels, inflammation and signaling pathways) leading to increased risk of breast cancer
- Insulin therapy and sulfonylurea were found to be mildly associated with increased breast cancer risk
Describe the association between prolactin and GH and breast cancer risk.
- GH induces production of IGFs in the liver
- IGF signaling contributes to breast development and is implicated in breast carcinogenesis
- higher levels of GH and prolactin were associated with higher breast cancer risk
Describe the association of oral contraceptives and breast cancer risk
Combined estrogen-progestogen oral contraceptives (OCs) increase the risk for breast, cervix, and liver cancers
Describe the association between mammographic breast density (MD) and breast cancer risk
- Mammographic density (MD) is the radiologic appearance of the breast that shows breast composition
- strong risk factor for breast cancer
- decreases with age
- assocaited with BMI, family hx, postmenopausal hormone use
- Potentially due to lots of stromal cells in this area that means abundance of growth factors that could stimulate epithelium in a noninvoluted breast thereby increasing risk of malignant transformation
Describe environmental factors that contribute to breast cancer risk.
Environmental causes possibly affect the breast the most during critical phases of development where mitotic activity and cell division are greater than later in life
1) Radiation: Ionizing radiation is a known mutagen and established carcinogen for breast cancer (accidentally or medically induced radiation i.e. diagnostic tests). Women treated with chest radiation for a pediatric or young adult cancer have a substantially increased risk of breast cancer
2) Diet: Prospective epidemiologic studies on diet and breast cancer risk fail to show an association that is consistent, strong, and statistically significant except for alcohol intake, being overweight, and weight gain after menopause. Potential mechanisms between fat inake and breast cancer risk:
- (1) fat may stimulate endogenous steroid hromone production (affecting weight gain and age of menarche)
- (2) fat interferes with immune/inflammatory function
- (3) fat influences gene expression
Carb quality may contribute to breast cancer risk in premenopausal women. Alcohol consumption increases risk (potentially through increased mammographic breast density). Soy products may reduce breast cancer risk by blocking estrogens. Iodine in diet may be protective in breast cancer risk.
3) Obesity: Increases cancer risk from cellular pathways that involve hormonal regulation, cellular proliferation, and immunity. However, associated with a reduced risk of premenopausal breast cancer. Obesity also associated with poor survival among women with breast cancer.
3) Environmental chemicals: difficulty to link to breast cancer due to need for life history of exposure. Xenoestrogens: synthetic chemicals that mimic actions of estrogens and found in pesticides, fuels, plastics, detergents, and drugs. Affects estrogen metabolism and contribute to breast cancer.
4) Physical Activity: reudces overall risk of breast cancer esp. in premenopausal or young postmenopausal women. May reduce invasiveness of breast cancer. Sedentary lifestyle may increase risk through increased insulin resistance, inflammation, and decreased immune function.
Describe the potential association between inheritance, genetics, and epigenetics and the risk of breast cancer.
- Hard to determine cause of breast cancer due to genetic heterogeneity (everyone having a different genetic profile)
- Risk of breast cancer increases with number of first-degree relatives affected
- Most important dominant genes: breast cancer susceptibility genes (BRCA1, BRCA 2)
- BRCA1 (breast cancer 1 gene)
- Located on chromosome 17, a tumor-suppressor gene so any mutation here may inhibit or slow its suppressor function leading to uncontrolled cell proliferation
- Carriers are at higher risk for breast and ovarian cancer
- BRCA2 (breast cancer 2 gene)
- Located on chromosome 13
- More likely in men who develop breast cancer
- BRCA1 (breast cancer 1 gene)
- Options for those with +ve BRCA1/BRCA2 mutation: surveillance for early cancer detection, risk factor avoidance, prophylactic surgery, promoting breast feeding, chemoprevention
Pathogenesis of breast cancer
- most are adenocarcinomas that first arise from ductal/lobular epithelium as carcinoma in situ (epithelial cell proliferation confined to ducts and lobules by basement membrane)
- tumors of the infiltrating (invasive) ductal type do not grow to a large size but metastasize early (accounts for ~70% of breast cancers)
- Breast cancer is hetergeous - not a single disease but has diverse molecular, biologic, phenotypic, and pathologic changes
- breast tissue stem cells thought to be cell of origin for all breast cancers
- Epithelial-to-mesenchymal transition (EMT): involved in tissue and organ generation during emrbyogenesis and is essential for driving tissue plasticity during development. Unintentional process during cancer progression.
Define the following terms:
Tumor dormancy
Vascular mimicry
Tumor dormancy: people with cancer where microscopic or occult cancerous lesions go into a latent/dormant phase in various stages of tumor progression
Vascular mimicry: blood supply pathway in tumours that is formed by tumour cells and is independent of endothelial cell-lined blood vessels → pathway facilitates perfusion to primary tumors
Ductal and Lobular Carcinoma in Situ (DCIS/LCIS)
DCIS: heterogenous group of proliferations limited to breast ducts and lobules without invasion of the basement membrane.
- presents with microcalcifications (low grade) or rod-shaped branching (high grade) on a mammogram
- Does not appear to progress from sequential steps of low grade to higher grades → most lesions of DCIS will not evolve to invasive cancer and if it done then it can be managed successfully
- ID’d via mammography (Detection and treatment of nonpalpable DCIS often overdiagnosed and overtreated)
LCIS: originates from terminal duct lobular unit. Has a uniform appearance (cells expand but do not disort involved spaces so the lobular structure is preserved)
- Cells grow in a noncohesive fashion usually due to loss of E-cadherin (loss of tumor-suppressive adhesion protein)
- Loss of cellular adhesion due to E-cadherin dysfunction results in a rounded shape without attachment to adjacent cells which increases risk of invasion
- found incidentally via biopsy (Not associated with calcifications or stromal reactions that produce mammographic densities)
- risk factor for invasive carcinoma and develops in some women over 20-30 years
- Treat: close clinical follow up, mammographic screening, tamoxifen, mastectomy
Clinical Manifestations of Breast cancer
Evaluation/Treatment of breast cancer
Clinical Manifestations:
- most are in upper outer quadrant where glandular tissue of breast is located
- first sign: usually painless lump
- palpable nodes in axilla
- retraction of tissue (dimpling)
- bone pain caused by metastasis to the vertebrae
- edema
Evaluation/Treatment: clinical breast exam, mammography, ultrasound, thermography, MRI, biopsy, hormone receptor assays, and gene expression profiling.
- Treatment: based on extent and cancer stage
- Surgery, radiation, chemo, hormone therapy, biologics.
What is the 2nd leading cause of cancer death and most frequently diagnosed cancer in men?
prostate cancer
Delayed/Absent Pubery in males
Definition: secondary sex characteristics developing later than typical (typically they tend to mature around 14-14.5 years of age with the first sign of maturity being testes enlargement and thinning of scrotal skin)
- in most cases (955) this is a normal physiologic event (hormone levels are nromal, HPG axis intact, maturation is slowly occurring)
- Treatment seldom needed unless causing psychosocial problems
- 5% are caused by some type of disruption of the hypothalamic-pituitary-gonadal axis or from systemic disease
Precocious puberty in males
Definition, Types/Forms
Definition: early onset of puberty, rare event. Sexual maturation before 9 y.o.
- Caused by many conditions, including lethal CNS tumors
- Requires thorough evaluation & al are treated by ID and removing underlying cause or administering appropriate hormones (disorder can be reversed)
Forms:
- Complete precocious puberty: premature development of appropriate characteristics for the child’s gender. HPO axis functionally normal but just premature. Can cause long bones to stop growing before child has reached normal height. 10% cases due to CNS tumor
- Partial precocious puberty: partial development of appropriate secondary sex characteristics. Premature adrenarche (growth of axillary and pubic hair) that tends to occur between 5-8 y.o. Can progress to complete precocious puberty. May be caused by estrogen-secreting neoplasms or a variant of normal pubertal development
- Mixed Precocious puberty: causes child to develop some secondary sex tracts of opposite gender. Common causes are due to adrogen-secreting tumours or adrenal hyperplasia
Urethritis
Definition, Causes, Clinical Manifestations, Treatment
Definition: inflammation of the urethra that is usually (not always) caused by STD
- Gonococcal urethritis: caused by Neiserria gonorrhoeae
- Nongonococcal urethritis: caused by other microorganisms
Causes: Non-sexual origins of inflammation/infection from urologic procedures, inserting foreign bodies into urethra, anatomic abnormalities, or trauma. Noninfectious urethritis is rare and assocaited with ingestion of wood or ethyl alcohol or turpentine
Sx: urethral tingling, itching, burning, frequent and urgency with urination. Purulent or clear mucous-like discharge from the urethra
Treatment: antibiotics and avoiding future exposure or mechanical irritation
Urethral Strictures
Definintion: Fibrotic narrowing of the urethra caused by scarring.
Causes: scars may be congenital but can present at any age & have a wide range of etiological factors (untreated urethral infection, trauma, urologic instrumentation)
Complications: prostatitis and infection 2’ to urinary stasis. Severe and prolonged obstruction can result in hydronephrosis and renal failure.
Clinical Manifestations: lower urinary tract symptoms or UTIs. Primary sx: diminished forced and caliber of urinary system. Urinary frequency and hesitancy, mild syuria, double urinary stream or spraying, dribbling after voiding.
Diagnosis: based on hx, physical exam, flow rates, cytoscopy.
Treatment: surgery
Phimosis
Paraphimosis
Both are due to foreskin being too tight to move easily over the glans penis. inability to retract foreskin is normal in infancy and is caused by congenital adhesions however these separate naturally with penile erections and are not an indication for circumcision0
Phimosis: foreskin cannot be retracted back over the glans (distal to proximal)
- Can occur at any age, most commonly caused by poor hygiene and chronic infection
- treat infection and then circumcision if necessary
- Complications: inflammation of the glans (balanitis) or prepuce (posthitis) and paraphimosis
Paraphimosis: foreskin is retracted and cannot be moved forward (reduced) to cover glans (proximal to distal)
- can constrict the penic and cause edema of the glans
- surgery needed to prevent necrosis of the glands due to constricted blood vessels if foreskin cannot be reduced manually
Peyronie Disease
Definition:“Bent nail syndrome” - a fibrotic condition that causes lateral curvature of the penis during erection. Mostly occurs in middle aged men.
Cause: unknown/
Pathophysiology: develops slowly and characterized by tough fibrous thickening of the fascia in the erectile tissue of the corpora cavernosa. Dense fibrous plaque palpable on the dorsum of the penile shaft. Local vasculitis-like inflammatory reaction occurs and decreased tissue oxygenation results in fibrosis and calcification.
Clinical Manifestations: painful erection and sex, poor erection distal to involved area. Possible impotence or unsatisfactory penetration. No pain when flaccid.
Treatment: no definitive treatment but can include pharmacologic agents and surgery.
Priapism
Definition: uncommon condition of prolonged penile erection. Usually painful and not assocaited with sexual arousal.
Causes: idiopathy (60% of cases), remaining 40% is assocaited with spinal cord trauma, sickle cell disease, leukemia, pelvic tumours, infections, penile trauma
Treatment: urologic emergency and needs to be treated within hours to prevent impotence. Conservative management: iced saline enemas, ketamine administration, spinal anesthesia
Balanitis
Definition: inflammation of the glans penis. Usually occurs with posthitis (inflammation of the prepuce). Associated with poor hygiene and phimosis.
Pathophysiology: glandular secretions (smegma), sloughed epithelial cells, and Myobacterium can irritate the glands directly or lead to infection. Commonly seen in men with poorly controlled DM and candidiasis
Treatment: antimicrobials. Possible circumcision to prevent recurrences.
Condyloma Acuminatum
- benign tumour caused by HPV (most common HPV 6 and 11) i.e. sexually transmitted
- can cause a common wart and moist surface of the external genitalia
- Giant condylomas affect older men
Penile Cancer
Incidence/Prevalence: carcinoma of the penis is rare.
Cause: exact cause unknown but risk factors include HPV infection, smoking, low SES, poor personal hygiene, and psoriasis. Reduced risk with circumcision at birth. Penile cancer is more common in men with phimosis and those with AIDS
Pathophysiology: mostly caused by SCC (easily treated if caught early)
