Week 2 Flashcards
What is a reduction in the frequency of the menstrual cycle referred to?
Oligomenorrhea
What is a complete cessation in the frequency of the menstrual cycle referred to?
Amenorrhea
What are the anterior pituitary hormones that control the menstruation cycle?
FSH and LH
What are the ovarian hormones that control the menstruation cycle?
Progesterone and estradiol (estrogen)
What is the role of estradiol in the context of the menstruation cycle?
Stimulate LH and FSH pre-ovulation
What is the role of progesterone in the context of the menstruation cycle?
Inhibits FSH and LH
Describe the peaks and troughs of the ovarian and anterior pituitary hormones during the menstrual cycle?
Progesterone is at a baseline low level during the start of the menstruation until ovulation is over when it steadily rises and peaks for the majority of the remainder of the cycle. Estrogen rises steadily from the start of the menstrual cycle until it peaks at ovulation. The anterior pituitary hormones (FSH and LH) are at a low level through the entirety of the menstrual cycle except for when the quickly peak and fall back down at ovulation.
What is Polycystic Ovarian Syndrome (PCOS)? How is diagnosed?
PCOS is the most common endocrine disorder of childbearing age women. It is diagnosed following the presence of two out of the three following criteria:
- Oligo-ovulation or anovulation
- Hyperandrogenism (clinical and/or biochemical)
- Polycystic ovaries on ultrasound
Is Polycystic Ovarian Syndrome inherited?
There is a familial basis in the development of PCOS (complex polygenic inheritance)
Describe the most common etiological theory of Polycystic Ovarian Syndrome?
The most widely accepted theory of the development of PCOS arises out of insulin resistance, which causes hyperinsulinemia. This in turn causes an increased ovarian production of androgen, which causes PCOS.
What is the principal source of excess androgen production in PCOS?
Ovaries
What is the principal source of excess androgen production in a woman who does not have PCOS?
Adrenal gland
What are some potential risk-factors for PCOS?
Metabolic syndrome and obesity are found in 50 and 60% of PCOS cases respectively.
What are the potential risks that arise as a result of PCOS?
Risk of diabetes, miscarriage, hypertension, and endometrial cancer.
What is the result of PCOS on the length of women’s menstrual cycle?
Increased cycle (>35 days)
What are the clinical signs of hyperandrogenism?
Hirsutism, deepening voice, male-pattern balding, increased muscle mass, acne
What is are the most common presentations in PCOS?
Infertility, hirsutism, amenorrhea, obesity
What is acanthosis nigricans? What syndrome can this be a result of?
Eruption characterized by thickening of the skin and increased pigmentation in the axilla, nape of the nick and under the breast. Part of PCOS
What is the difference between hirsutism and hypertrichosis?
Hypertrichosis is the increase in total body hair, whereas hirsutism is the excess in terminal (thick, pigmented) body hair in a male distribution.
What is are the most common presentations in PCOS?
Infertility, hirsutism, amenorrhea, obesity
What is the commonest cause of hirsutism? What are other potential diagnoses?
PCOS is the commonest cause, although it could also be late-onset congenital adrenal hyperplasia, or Cushing’s syndrome.
What are the investigations to do when aiming to diagnose PCOS?
Free and total plasma testosterone, gonadotrophins, prolactin (mildly raised in PCOS)
What imaging technique is most commonly used in the diagnosis of PCOS?
Ultrasound to image the ovaries, and see whether cysts are present on the ovaries or not?
What is the management plan of PCOS contingent on?
It is contingent on the presenting complaints of the patient. This essentially means that the treatment plan will depend on what clinical presentation the patient has (hirsutism, acne, amenorrhea…)
How quickly does the treatment for PCOS usually take to show effects?
It usually very slow (6-9 months), and it isn’t especially effective.
What is the primary approach to PCOS treatment?
The primary approach is non-pharmacological. Instead, lifestyle changes (weight, diet, exercise).
What are the pharmacological treatments used in PCOS? Why are each one of them used?
- Oral contraceptives
o Has androgen-lowering effects (by increasing SHBG and lowering LH and FSH)
o Protects endometrium and perhaps prevents endometrial hyperplasia/cancer - Insulin sensitizers (e.g. metformin)
o Targets the etiology of the disease (insulin resistance)
o May also help with systemic issues (e.g. obesity)
o May restore ovulation - Antiandrogen drugs (e.g. spironolactone)
o Antagonize the effects of testosterone
o Has antiandrogen effects
What drug is used alongside metformin to increase chances of ovulation for fertility problems associated with PCOS? What class of drug is it and describe its mechanism?
Clomiphene. It is an SERM (selective estrogen receptor modulator), which stimulate estrogen receptors and increase the likelihood of ovulation.
What is the difference between primary and secondary amenorrhea?
Primary amenorrhea can be described as:
- The absence in menstruation in a girl who has reached age 14, accompanied by the failure to develop secondary sexual characteristics
- The absence in menstruation in a girl who has reached age 16, when growth and secondary sexual characteristics are normal
Primary amenorrhea can be described as:
- Secondary absence of menses for six months in a woman who has menstruated before
What are the possible causes of amenorrhea?
A. Disorder of outflow tract and/or uterus
a. Anatomical (possibly congenital) defects with the reproductive tract, not allowing the outflow of blood
B. Disorders of ovary
a. Congenital disease (e.g. Turner’s)
b. Acquired conditions causing premature ovarian failure (e.g. autoimmune, trauma, chemotherapy …)
C. Disorders of pituitary
D. Disorders of hypothalamus
What is Mullerian agenesis?
Complete absence of the uterus, cervix, and upper 2/3 of the vagina. Otherwise normal development.
What is androgen insensitivity syndrome?
A syndrome by which an individual has an XY genotype, but due to the lack of response to androgen by its receptors, develops female features (breasts, inconclusive genitalia, lack of hair …)
What is hypergonadotropic hypogonadism characterized by?
High LH and FSH levels, with an inability for the gonad to respond or detect the LH and FSH levels.
What is an example of a condition with hypergonadotropic hypogonadism?
Turner’s syndrome
What is Turner’s syndrome?
A syndrome characterized by the fact that the individual will only have 45 chromosomes and will be missing one of their sex chromosomes, resulting in a XO sex chromosome. This means that while they are female as they are missing the Y chromosome, they only have one chromosome meaning that there are clinical features different to other individuals.
What are some clinical features of Turner’s syndrome?
Amenorrhea, constriction of the aorta, short stature, failure of secondary sexual characteristics development, webbing of the neck …
What pituitary cause would lead to amenorrhea? What mechanism does this happen through?
Hypogonadotropic hypogonadism – low LH and FSH and in turn low estrogen. Caused by one of many possible conditions of the pituitary including Cushing’s syndrome, pituitary tumors, prolactinoma …
What hypothalamic cause would lead to amenorrhea? What mechanism does this happen through?
Hypogonadotropic hypogonadism – low LH and FSH and in turn low estrogen. Caused by one of many possible reasons:
- Low weight: Heavy physical stress causes the hypothalamus not to release hormones (GnRH) as the body is unable to carry a child, therefore going through amenorrhea
- Kallman’s syndrome
- Post-pill amenorrhea: Can take up to 12-18 months for periods to start again after halting the use of the pill
- Tumors
What is Kallman’s syndrome? What are some features? What is the treatment?
An X-linked recessive mutation in the KAL gene. Results in the lack of migration of GnRH neurons which ultimately results in hypogonadotropic hypogonadism. Could present with anosmia, midline facial defects, and absence of secondary sexual characteristics. The treatment is hormone replacement therapy.
What would high/low levels of FSH and LH show about the root cause of an amenorrhea?
If FSH and LH are high, it’s hypergonadotropic hypogonadism, meaning it’s an ovarian problem, whereas if they’re low, it’s hypogonadotropic hypogonadism, meaning it’s pituitary or hypothalamic.
What would be the needed initial workup for a patient presenting with amenorrhea?
- History and physical examination
- Rule out pregnancy
- Measure plasma LH, FSH (see if high or low to determine root cause), TSH, FT4, testosterone
- Imaging (ovaries, pituitary)
- May need to karyotype if primary amenorrhea to check for genetic component
What would high/low levels of FSH and LH show about the root cause of an amenorrhea?
If FSH and LH are high, it’s hypergonadotropic hypogonadism, meaning it’s an ovarian problem, whereas if they’re
What is the effect of LH on the male reproductive system?
Stimulates Leydig cells to produce testosterone.
What is the effect of FSH on the male reproductive system?
Stimulates the production and maturation of spermatozoa.
Where in the testis are spermatozoa produced? What are their path post-production?
They are produced in the body of the testis, where they will then make their way into the head of the epididymis, and travel inside the epididymis into its tail where it will then continue into the vas deferens which will travel inside the spermatic cord into the prostatic bladder and merge into the urethra.
What is this picture showing?
This picture is showing a tubule inside the body of the testes. This tubule contains purple-stained nuclei around the outside, which are spermatogonia, which, with time, mature to become spermatozoa and merge in the middle of the tubule (white part).
What is the specifically, the most common type of testicular tumor?
Most testicular tumors are germ cell tumors (about 95% of tumors), and specifically, seminomas.
What is the main difference between seminomatous vs non-seminomatous germ cell tumors?
Age – seminomas are usually within a slightly older age range compared to non-seminoma (30-50 vs 20-30)
Are most germ cell tumors malignant or benign - In the testes? In the ovaries?
In the testes, most germ cell tumors are malignant, whereas most germ cell tumors are benign in the ovaries.
What is a trademark risk factor for testicular germ cell tumors?
Cryptorchidism (testes herniate to the abdomen)
What are the types of germ cell tumors in the testes?
Seminomatous vs non-seminomatous germ cell tumors
What is the expected clinical presentation of a patient with testicular germ cell neoplasms?
Enlarged testis, metastases (e.g. mass in the abdomen …)
What would the following CXR indicate as a differential diagnosis?
Cannonball metastases to the lung secondary to testicular germ cell neoplasms.
What are some tumor markers that can be used in the initial diagnosis and to detect recurrence of testicular germ cell tumors?
Seminomatous: Placental alkaline phosphatase (PLAP)
Non-seminomatous: Alpha-fetoprotein (AFP), beta-human chorionic gonadotrophin (BHCG)
What is the prognosis of patients with germ cell tumors?
Germ cell tumors are sensitive to chemotherapy and radiation, so unless there is widespread disseminated disease, the cure is likely.
Are most germ cell tumors malignant or benign - In the testes? In the ovaries?
In the testes, most germ cell tumors are malignant, whereas most germ cell tumors are benign in the ovaries.
Give an example of a non-germ cell tumor?
Leydig cell tumor
What are Leydig cells? What is their function?
Cells in between seminiferous tubules that produce testosterone when stimulated by LH.
What are the clinical signs of Leydig cell tumors and how do they relate to their homeostatic function?
Leydig cells in homeostasis produce testosterone when stimulated by LH. When it becomes a neoplasm, Leydig cells start producing uncontrolled levels of testosterone, resulting in clinical signs such as raised masculinsing effects in women and features of precocious puberty in children.
What anatomical feature runs straight down the middle of the prostate?
The prostatic urethra
What condition affects over 75% of men over the age of 70?
Benign prostatic hyperplasia
What is benign prostatic hyperplasia?
A common, non-neoplastic lesion, which causes the hyperplasia of both glands and the stroma.
What is the most telling clinical sign of benign prostatic hyperplasia?
Urinary outflow symptoms
Does benign prostatic hyperplasia increase the risk of developing a neoplastic lesion?
No, benign prostatic hyperplasia is not a premalignant lesion.
What is trabeculation of the bladder? What is it caused by in the scope of benign prostatic hyperplasia?
Trabeculation of the urinary bladder is when hypertrophy of the bladder muscles occurs as a result of a urinary outflow problem. This causes the bladder to have to contract harder to push urine out through the urethra, and causes trabeculation of the bladder. In the scope of BPH, it is caused by the decreased urinary outflow of the prostatic bladder, which necessitates more contraction of the bladder which in turn, causes the trabeculations.
What is the most common cancer in men?
Prostate carcinoma
What is a differences between prostatic hyperplasia and carcinoma?
Prostatic hyperplasia usually starts in the periurethral tissue (around the urethra), whereas carcinomas usually start on the edge of the prostate and slowly makes its way to the middle.
What is the precursor lesion for prostatic carcinomas called?
Prostatic intraepithelial neoplasia
What are the most common presentations which uncover prostatic carcinoma?
Urinary outflow symptoms
Metastases
Incidental findings/screening
What investigations lead to the diagnosis of prostatic carcinoma?
A blood serology can show elevated PSA (prostatic specific antigen), an MRI can be conducted, a digital rectal exam can be conducted, but the way it is confirmed is always a transrectal ultrasound guided biopsy.
What are the management options for prostatic carcinoma?
Surgery, radiotherapy, or hormone manipulation – usually the reduction of androgen stimulation has been shown to hinder the growth of the carcinoma.
What are the two major components of the uterus?
Myometrium and endometrium
What are the endometrium and the myometrium? What are they composed of?
The myometrium is the layer of bundles of smooth muscles which forms the wall of the uterus. The endometrium is what lines the internal cavity, composed of glands embedded in the cellular stroma.
What are the three main parts of a woman’s menstrual cycle?
Proliferative phase, ovulation, and secretory phase.
Down below are two histological images showing the lining of the uterus. Name the name of the layer lining the uterus, and name the menstrual phase they’re currently at?
1) Secretory phase
2) Proliferative phase
What are the major factors in infertility/subfertility?
Vascular
Infectious
Neoplastic
Drugs
Idiopathic
Connective tissue disorder
Autoimmune
Trauma
Endocrine
What is endometriosis?
It describes the presence of ectopic endometrial tissue (glands) at a site outside the uterus (instead of lining the uterine wall).
What are the most common sites finding endometrial tissue in endometriosis?
- Ovaries
- Uterine
- Pouch of Douglas
- Pelvic peritoneum
- Large and small bowel and appendix
What is the usual clinical presentation of a woman suffering from endometriosis?
Infertility, dysmenorrhea, pelvic pain
What are the two hypotheses for the pathogenesis of endometriosis?
- Ectopic endometrium has arisen from uterine endometrium
- Cells outside the uterus have the capacity to give rise to endometrial tissue
What is the related disorder with endometriosis and what does it describe?
Adenomyosis: it describes a condition by which endometrial glands are present inside of the myometrium.
What is the most common cancer of the female genital tract?
Endometrial adenocarcinoma
What are the different types of endometrial adenocarcinomas? Which one is more common?
Endometrioid adenocarcinoma – Most common (80% of cases)
Non-endometrioid adenocarcinoma (serous type)
What is the endometrial intraepithelial neoplasia (EIN)? What is its etiology and risk factors?
It is premalignant lesion of the endometrium, and arises in response to increased estrogen stimulation. This can be due to a number of factors such as the following:
- Obesity
- Menopause
- PCOS
- Prolonged administration of ostogenic substances (combined pill, HRT …)
Endometrial adenocarcinomas are graded I, II, or III. What is the meaning of the grade given to the malignancy?
It grades how alike to normal tissue the malignancy is. Grade I describes a malignancy in which its constituent cells resemble normal endometrial tissue whereas grade III describes tissue that has completely changed from the initial cell type.
What is the expected patient presenting with a non-endometrioid adenocarcinoma, and what is a key mutation of this malignancy?
Non-endometrioid adenocarcinomas usually arise in older, post-menopausal women as it arises in inactive, atrophic endometrium. The key mutation found in over 90% of all non-endometrioid adenocarcinomas is the p53 mutation.
What is post-menopausal bleed a clinical feature of?
A post-menopausal bleed is considered endometrial cancer until proven otherwise.
What clinical method is the diagnosis of endometrial cancer made through?
Biopsy and histological examination of the tissue obtained.
What is the treatment for endometrial adenocarcinomas?
Total abdominal hysterectomy (TAH) with bilateral salpingo-oophorectomy (BSO), followed by chemotherapy or radiotherapy.
What is the most common benign tumor of the female genital tract?
Leiomyoma (fibroid)
What are leiomyomas made out of and where in the body are they located?
Leiomyomas are made out of smooth muscle and are located in the myometrium of the uterus.
What usually leads to the diagnosis of leiomyomas?
Submucosal leiomyomas usually can cause abnormal bleeding, and in some cases compress the bladder.
Can women with leiomyomas be pregnant and give birth?
It is possible for them to get pregnant and give birth, although leiomyomas increase the risk of miscarriage, uterine malcontraction, and postpartum hemorrhage.
What are some characteristics of ovarian neoplasms, and what gives indication as to whether they are most likely malignant or not?
They may be solid or cystic, benign or malignant. However, the more solid, the more chance for it to be malignant.
What are borderline lesions in ovarian neoplasms?
Lesions that could, but have a low risk of becoming a malignant tumor.
What is the difference between the endo and ectocervix histologically?
The endocervix and the ectocervix form the entrance of the cervix from the vagina and they are made up of two distinct types of epitheliums. The ectocervix is made up of simple squamous epithelium whereas the endocervix is made up of columnar, mucus secreting epithelium.
Why is the histological difference between endo and ectocervix relevant clinically?
The reason it is clinically relevant is that the squamo-columnar junction is the junction where the two types of epithelium meet and this transformation zone is where cervical cancer arise from.
What is one of the biggest known risk factors for cervical cancer? Specifically? Why?
HPV-16 and HPV-18. They have specific oncogenes that dysregulate DNA repair and makes individual more prone to developing a malignancy.
Is HPV infection alone enough to cause cancer?
No, alone it is not sufficient to cause cancer, although the individual would be at a higher risk for cervical carcinoma.
What is the cervical precursor legion called? How many classes are there?
Cervical Intraepithelial Neoplasia (CIN). Three classes – CIN 1 (mild dysplasia), CIN 2 (moderate dysplasia, CIN 3 (severe dysplasia)
What is the most common cervical cancer?
Squamous cell carcinoma
What are the different stages of cervical cancer?
Stage 0: Carcinoma in-situ (CIN 3), has not breached the basement membrane
Stage 1: Carcinoma confined to the cervix
Stage 2: Carcinoma spread beyond the cervix but not to pelvic wall or lower 1/3 of the vagina
Stage 3: Carcinoma reached pelvic wall or lower 1/3 of the vagina
Stage 4: Carcinoma invaded bladder, rectum or metastasized.
What is the best prevention method for cervical cancer?
Cervical screening, HPV vaccine.
Which germ layer of the trilaminar disk do the genital and urinary systems come from?
The mesoderm (more specifically the intermediate mesoderm)
What are the three kidney systems from which the kidney develop?
The pronephros, the mesonephros and the metanephros
What is a gonad?
A gonad is a gamete-producing organ; can either be the testis or the ovary
Describe the development of the gamete-producing organs?
Indifferent stage: In the indifferent stage, the gonads are still not differentiated, and the yolk sack contains primordial germ cells which migrate into the longitudinal (gonadal) ridges. This will determine the development of the gonad into ovary or testis as the primordial germ cells carry XX or XY chromosomes. This will the cause epithelial cells to penetrate the mesenchyme forming the primitive sex cords.
What is the effect of primordial germ cells not reaching the longitudinal ridge?
The gonad will remain indifferent or absent.
What gene determines sex in males? Where is it present
SRY gene on the Y chromosome
What specialized cells produce testosterone?
Leydig cells
How many initial ducts that embryos have in the indifferent stage and what are they? What happens to them when the gonad differentiate into one of the sexes?
There are two initial ducts in the embryological stages called the mesonephric and the paramesonephric ducts. In females, the paramesonephric ducts give rise to the uterine tubes, uterus, and upper portion of the vagina, while the mesonephric ducts degenerate due to the absence of male androgens. In males, the paramesonephric duct will atrophy and the mesonephric will elongate and form the epididymis, the vas deferens, and the seminal vesicle.
What is the embryological origin of the epididymis? The seminal vesicle? The prostate? The vas deferens?
The epididymis, the vas deferens, and the seminal vesicle all derive from the mesonephric duct, while the prostate arises as an outgrowth from the urethra.
What is the anatomical area in which the vas deferens joins the seminal vesicle into the urethra?
The ejaculatory duct.
Describe the development of the paramesonephric duct in the female embryo?
The tail end of the paramesonephric duct meets its counterpart and fuse to form the uterine cavity. The cranial and middle portion of the paramesonephric duct develop into the uterine tubes.
What is the name of the wing-like expansions that canalize vaginal outgrowth?
Vaginal fornixes
What is the most common abnormality of the uterus during development? Describe it?
Complete bicornuate uterus. Occurs when the uterine cavity is divided into two chambers divided by a septum.
What is the topmost part of the uterus called?
The fundus
What is the gubernaculum? What does it do?
A fibrous tissue connecting from the inferior ball of the testis to the scrotum. Week by week during development it gradually pulls the testis down from its starting position in the posterior abdominal wall at week 12 to the scrotum at week 33.
What anatomical feature do the testis pass through while descending to the scrotum?
The inguinal canal.
How long after birth should testes descend on their own before seeking treatment?
6 months
Where are most undescended testes found?
In the suprascrotal area.
What is the difference between true vs ectopic undescended testes?
True undescended testis: where testis is absent from the scrotum but lies along the line of testicular descent.
Ectopic testis: where the testis is found away from the normal path of decent.
