37. Menstrual Cycle Physiology Flashcards
Period of change when the AP gland begins to secrete progressively more FSH and LH leading to normal monthly menstrual cycles
Puberty
_____ = breast development associated with puberty
Thelarche
_____ =increased adrenal androgen secretion associated with puberty
Adrenarch
Woman’s first menstrual period; avg age is 12.5 years
Menarche
Rhythmical secretion of hormones leading to physical changes in the ovaries and uterus, including release of an ovum and preparation of the endometrium for implantation; avg 28 days
Menstrual cycle
Absence of menses
Amenorrhea
Absence of menarch by age 15, with secondary sexual development
Primary amenorrhea
Menstrual periods lasting >35 days
Oligomenorrhea
Menstrual periods lasting <21 days
Polymenorrhea
Dysmenorrhea
Painful menses
Metrorrhagia
Frequent or irregular menstruation
Menorrhagia
Heavy menstrual bleeding
Menometrorrhagia
Heavy irregular bleeding
Which of the following organs is not directly involved with the female menstrual cycle?
A. Ovary B. Posterior pituitary C. Uterus D. Anterior pituitary E. Hypothalamus
B. Posterior pituitary
What phases of the ovarian cycle line up with the phases of the endometrial cycle?
Ovarian follicular phase lines up with endometrial proliferative phase
Ovarian luteal phase lines up with endometrial secretory phase
HPA regulates the menstrual cycle beginning with secretion of _____ from the hypothalamus in a _____ manner. Gonadotrophic cells become more sensitive to this hormone during the _____ phase
GnRH; pulsatile; follicular
The anterior pituitary releases ___ and ____ in response to GnRH from the hypothalamus, contributing to menstrual cycle regulation
LH; FSH
LH and FSH from the AP act on the ovarian theca cells to produce _____ and _______ hormones, while simultaneously acting on the ovarian granulosa cells to produce ____ and _____ hormones
Androgens; progestin
Estrogen; inhibin
Females are born with 1-2 million ova arrested in _________. These are known as primordial follicles, which are nourished by _______ cells, which also serve the role of producing oocyte maturation inhibiting factor
Prophase 1; granulosa
After puberty, the primordial follicles develop when FSH and LH are released from the AP. They then arrest in _______ unless fertilization occurs
Metaphase 2
The follicular phase of the ovarian cycle begins at the onset of _______. FSH stimulates follicle development and granulosa cells produce ________, causing endometrial growth and maturation as well as an LH surge. The follicular phase is complete at around day ____, the day of that LH surge
Menses; estradiol; 14
2 days prior to menstruation, there is a release of negative feedback on the H and AP, leading to increased production of _____
On day 1 of the menstrual cycle, the above hormone recruits several follicles. The follicles produce low levels of _____ and _____, resulting in renewed negative feedback on ______
FSH; estrogen; inhibin B; FSH
Once follicles exert negative feedback on FSH via production of estrogen and inhibin B, ____ and _____ levels also decrease, which causes an increase in pulsatile frequency of GnRH pulsations, causing an increase in the ____:____ ratio
Progesterone; estrogen; LH:FSH
The increase in frequency of GnRH pulsations causing an increase in the LH:FSH ratio (thus decreased FSH) causes follicular ______, and only one dominant follicle typically remains
The dominant follicle remains dependent on FSH. It produces ______ and _______. FSH induces expression of LH receptors in the mural granulosa cells of the dominant follicle
Atresia
Estradiol-17B; inhibin B
The luteal phase of the ovarian cycle begins on the day of the LH surge, day 14. At that time, the follicle becomes the __________. Luteal cells produce ______ and ______, promoting further endometrial growth and development
This phase ends at the onset of menses
Corpus luteum; progesterone; estrogen
When circulating _____ exceeds 200 pg/mL for 50 hours, it exerts a ________ feedback mechanism on the AP causing a surge of LH
Estrogen; positive
What happens as a result of the LH surge on day 14? (3 major events)
- Primary oocyte completes meiosis, arrests in metaphase 2
- Wall of follicle and ovary at the stigma are broken down
- Mural granulosa cells and theca cells are restructured —> corpus luteum
During the luteal phase, the corpus luteum produces progesterone, estrogen, and _______, which exerts negative feedback on the AP. So estrogen may be >200pg/mL, but the positive feedback mechanism is inhibited by the elevated progesterone. FSH and LH are at _____ levels at this point in time
Inhibin A; basal
______ is required for corpus luteum function. If implantation does occur, ______ maintains the corpus luteum. In the absence of either of these hormones, the corpus luteum regresses and menstruation occurs
LH; hCG
In the absence of LH or hCG, as well as low progesterone, low estrogen, and low inhibin A, negative feedback on the hypothalamus is released, the corpus luteum becomes the _______, and menses occurs
Corpus albicans
A healthy 6 year old girl is brought to the pediatrician by her mother because she has had vaginal bleeding for 5 days. The patient and her mother deny having taken any medication and initial screening for sexual abuse is negative. She has been doing well in school and has no complaints of head pain or changes in her vision. Her BMI is normal. On physical exam she is normal for her age, without pubertal changes. Based on her clinical presentation, you suspect:
A. Sexual abuse B. Early maturation of the HPA axis C. Foreign body D. Spontaneous abortion (miscarriage) E. Endometrial hyperplasia
C. Foreign body
During the follicular phase, estradiol from the ovary exerts _______ feedback on the AP. During midcycle, estradiol from the ovary exerts ______ feedback on the AP. During the luteal phase, ______ from the ovary exerts negative feedback on the AP
Negative; positive; progesterone
What cell type of the ovary has LH receptors, no aromatase, and produces androgens (primarily androstenedione)?
Theca cells
What cell type of the ovary has LH and FSH receptors, contains aromatase, and produces inhibins?
Granulosa cells
T/F: Estrogen and progesterone are transported loosely bound to plasma proteins in circulation
True
During the follicular phase, the follicle primarily produces _______
During the luteal phase, the follicle primarily produces ______
Estradiol
Progestins
During the follicular phase, LH primes the _____ cell to convert cholesterol to androstenedione (these cells lack aromatase). Androstenedione diffuses into _______ cells
Theca; granulosa
_____ stimulates aromatase in granulosa cells
FSH
Androstenedione can be converted to estradiol via _____ enzyme in _____ cells
Aromatase; granulosa
What hormone is responsible for maturation and maintenance of the fallopian tubes, uterus, cervix, and vagina?
Estrogen
Estrogen is associated with vaginal epithelium _______ —> stratified squamous. It is also associated with glandular tissue proliferation and enhanced cilia activity in the ______ ______
Cuboidal; fallopian tubes
What form of estrogen is most potent in the body?
Beta-estradiol > estrone > estriol
T/F: estrogen exerts negative feedback on the hypothalamus and pituitary at both high and low concentrations
True
Where is estrogen metabolized? Excreted?
Metabolized in liver; excreted in urine
[so decreased liver function leads to increased activity of estrogen in the body]
What hormone maintains the secretory activity of the uterus during the luteal phase and prepares the uterus for implantation (decidualization)?
Progesterone
Estrogen is responsible for development of female secondary sex characteristics such as breast development. What aspects of breast development are promoted by estrogen?
Stromal tissue development
Growth of ductile system
Deposition of fat
Estrogen maintains pregnancy and lowers the uterine threshold to _____ stimuli. It also stimulates prolactin secretion
Contractile
What role does progesterone play in breast development?
Development of lobules and alveoli to ensure secretory capabilities if stimulated by prolactin
Progesterone maintains pregnancy and ______ the uterine threshold to contractile stimuli during pregnancy
Raises
[contrast with estrogen which lowers uterine threshold to contractile stimuli during preg]
Progesterone is metabolized in the ____ and excreted in the ____
Liver; urine
[rate of progesterone formation can be estimated from urine excretion rate — useful for counselling infertility pts]
When is progesterone concentration highest?
Between ovulation and the beginning of menstruation (day 14-28)
______ acts on the hypothalamus to increase the set point for thermoregulation about 0.5 degrees during the time of ovulation
______ serves a neuroprotective function at this time
Progesterone
Estrogen
Disintegration of the corpus luteum (d/t lack of fertilization) causes a subsequent _____ in basal body temperature, and menstruation occurs
Drop
Inhibins are produced by granulosa cells of the follicle when stimulated by _____. ____ produced just prior to ovulation also stimulates production
FSH; LH
_______, produced by granulosa cells of the follicle, inhibit FSH production by gonadotropes but do not have an effect on GnRH itself (via negative feedback)
Inhibins
T/F: inhibins inhibit LH production
False; inhibins have no effect on LH (activins have no effect on LH either)
Inhibins cause a _____ in intraovarian production of androgens, and therefore estrogens
Decrease
Compare/contrast structures of inhibins vs. activins
Inhibins = 1 alpha, 1 beta subunit
Activins = 2 beta subunits
______ are produced by granulosa cells as well as in several extragonadal tissues. They stimulate production of FSH by gonadotropes, independent of GnRH action
Activins
Activins increase intraovarian production of ______, but have no effect on LH
Estrogens
The mid-cycle surge of LH leads to increased production of progesterone to maintain the endometrial lining of the uterus. How many days pass between the LH surge and corpus luteum regression (menses)?
A. 10 days
B. 14 days
C. 18 days
D. 28 days
B. 14 days
[regardless of cycle length, ovulation occurs 14 days prior to start of menses]
The menstrual cycle results in 25-35 mL of total blood loss. A decrease in _____ and _____ indicate corpus luteum regression, leading to withdrawal of hormonal support from endometrium.
Estradiol; progesterone
During menses, _______ breakdown the stratum functionalis. ______ lead to hypoxic necrosis of the spiral arteries, and shedding of the functional layer occurs
Matrix Metalloproteinases (MMPs); prostaglandins
During the proliferative phase, antral follicles begin producing ______ (especially with dominant follicle)
The endometrium proliferates 0.5mm to 5mm, and there is development of straight or coiled uterine glands
This induces expression of _____ receptors, allowing endometrium to respond to this hormone during the luteal phase
Estradiol; progesterone
During the secretory phase of the endometrial cycle, ______ inhibits endometrial growth by downregulating estrogen receptors (this is done by activating enzymes that inactivate estrogen and convert estradiol —> ______)
Progesterone; estrone
During the secretory phase of the endometrial cycle, progesterone induces differentiation of epithelial and ____ cells, as well as induces production of nutrient rich secretion from uterine glands. In addition, it alters the _____of the surface epithelium
Stromal; adhesivity
What is the most common cause of congenital (primary) hypogonadism?
Turner syndrome (gonadal dysgenesis)
Those with turner syndrome have what genotype/phenotype combo?
Female; 45, XO
Describe turner syndrome
Internal and external genitalia are female but ovaries fail to develop
Serum FSH is very high bc it is trying to stimulate ovaries that are not functional. Germ cells do not develop, ovaries appear as a CT filled streak = STREAK OVARIES
Characteristics seen in someone with Turners syndrome
Short stature Shield chest Bicuspid aortic valve Coarctation of aorta Low set ears Short 4th metacarpals Lymphatic defects Sexual infantilism Amenorrhea
Diagnosis of PCOS requires 2/3 of what 3 criteria?
- Amenorrhea
- Evidence of excess androgen secretion (acne, hirsutism)
- Polycystic ovaries
[ovaries described as “string of pearls”]
PCOS results with a continuous secretion of _____, leading to ovarian enlargement and excess androgen production from _____ cells
LH; theca
In PCOS, the elevated levels of androgens result in some being converted to _____ in ______ tissue. Increased levels of this hormone feed back to inhibit FSH secretion, which inhibits follicular maturation and decreases the release of _______
Estrone; adipose; 17B-estradiol
Symptoms of PCOS
Menstrual dysfunction (amenorrhea)
Hyperandrogenism (acne, hirsutism, male pattern hair loss)
Polycystic ovaries
Metabolic issues/cardiovascular risks (obesity, insulin resistance, T2D)
Infertility
Endometriosis occurs when endometrial glands implant outside the endometrial cavity. Where are the 3 most common locations?
Ovary
Pelvis
Peritoneum
What are theories as to how endometriosis develops?
Retrograde flow
Metaplastic transformation of multipotent cells
Lymphatic transport of endometrial tissue
Signs/symptoms of endometriosis
Cyclic abdominopelvic pain Dysmenorrhea Dyspareunia Dyschezia Heavy menstrual bleeding Tenderness on vaginal exam Infertility
Tx for endometriosis
NSAIDs OCPs Progestins and other hormones Laparascopic removal GnRH agonist
Define menopause
12 consecutive months without menstruation; avg age = 51
Hormonal changes during menopause
Decreased estrogen, along with increased LH and FSH d/t lack of negative feedback
Estrone, synthesized from circulating androgens, becomes primary form of estrogen
Causes of menopause
Natural
Premature ovarian failure
Surgical
Chemotherapy
Signs/symptoms of menopause
Irregular menstruation Vaginal dryness Hot flashes Night sweats Sleep problems Mood changes Dec. metabolism, weight gain Thinning hair, dry skin Loss of breast fullness
Tx for menopause
Relief of s/s — estrogen therapy (vaginal, topical, oral)
Management of comorbid conditions
A 20 year old female college cross country runner comes to the infirmary with a chief complaint of no periods and believes she may be pregnant. She has not had a menstrual cycle in 3 months and would like a pregnancy test. Your nurse ran a pregnancy test on the urine specimen the patient provided prior to being roomed and the result is negative. On further questioning she denies nausea, vomiting, lightheadedness, dizziness, chest pain, palpitations, hot flashes, mood swings, nipple discharge, any changes in her vision and any new male pattern hair growth. She is sexually active in a monogamous relationship and uses condoms 100% of the time. She has run cross country since middle school and has really ramped up her training and discipline with her diet this year so that she can be a contender at the Olympic trials.
On arrival, her vitals were: BP 102/65, P 54, T 98F, BMI 16
You suspect:
A. Primary amenorrhea B. Secondary amenorrhea C. Pregnancy D. Ovarian failure E. Prolactinoma
B. Secondary amenorrhea
