Endocrinology of the Ovary & Female Reproductive Tract Step 1 Practice Exam

C — Correct. Physiologic GnRH is pulsatile (every 60–90 min), which is required to keep gonadotropes responsive. Continuous leuprolide (GnRH agonist) produces sustained receptor occupancy → receptor internalization + downstream signaling desensitization → ↓LH/FSH → ↓testicular testosterone → "chemical castration." The initial T flare (weeks 1–2) reflects early receptor activation before desensitization takes hold. To blunt the flare, antiandrogens (e.g., flutamide, bicalutamide) are co-administered. GnRH antagonists (degarelix, cetrorelix) suppress LH/FSH immediately without any flare.

C — Correct. Aromatase (CYP19) converts androgens (androstenedione, testosterone) → estrogens (estrone, estradiol). In premenopausal women, granulosa cells aromatize thecal androgens. In postmenopausal women, ovarian aromatase is gone and adipose tissue becomes the dominant site. Anastrozole/letrozole/exemestane block aromatase → very low peripheral estrogen → benefits ER+ breast cancer but worsens bone density and joint symptoms. Compare: tamoxifen is a SERM (ER antagonist in breast, agonist in bone and endometrium → but ↑ endometrial cancer risk).

B — Correct. hCG and LH share an α-subunit and have nearly identical β-subunits; both bind the same LH receptor. A single hCG bolus mimics the endogenous LH surge → resumes oocyte meiosis I (extrusion of first polar body → secondary oocyte arrested at metaphase II), triggers follicular rupture ~36 hours later, and begins luteinization of granulosa. Timing is critical: retrieve before natural ovulation spills the oocyte. Patients have been downregulated with GnRH agonists/antagonists to suppress their own LH surge so the hCG "trigger" is controlled.

B — Correct. During weeks 0–10 of gestation, progesterone (required to maintain the pregnant endometrium) comes from the corpus luteum, which is maintained by trophoblast-derived hCG. The luteal–placental shift occurs at ~8–10 weeks, when the placenta becomes the dominant progesterone source. Losing the CL before this handoff → abrupt progesterone drop → miscarriage. Clinical lesson: supplement with exogenous progesterone if CL is lost before week 10. Natural progesterone transitions smoothly once placenta takes over.

B — Correct. The histology describes the secretory (luteal) phase endometrium — driven by progesterone from the corpus luteum. Key features: tortuous glands with sub-nuclear then supra-nuclear glycogen vacuoles, stromal edema progressing to pre-decidualization, and prominent spiral arterioles. Progesterone peaks on day 21 of a 28-day cycle (mid-luteal). Timing biopsies for "day 21 progesterone" in infertility evaluation assesses CL function. Without adequate progesterone, implantation fails.

B — Correct. Primary amenorrhea + short stature + webbed neck + shield chest + arm-leg BP gradient = Turner syndrome (45,XO) with coarctation of the aorta. ↑↑FSH/LH with ↓E2 is hypergonadotropic hypogonadism from streak gonads — ovarian follicles undergo accelerated atresia before birth. Cardiovascular complications drive mortality: bicuspid aortic valve (most common defect), coarctation of aorta (differential arm/leg pressures), aortic root dilatation/dissection. Also screen: thyroid (Hashimoto), renal (horseshoe kidney), skeletal (scoliosis). Treatment: GH in childhood + cyclic E2/P at puberty; fertility via donor oocyte.

C — Correct. Kallmann syndrome = delayed puberty + anosmia = failed migration of GnRH-releasing neurons (and olfactory neurons) from their shared origin in the olfactory placode to the medial basal hypothalamus. KAL1/ANOS1 is X-linked recessive; autosomal forms include FGFR1. Labs confirm hypogonadotropic hypogonadism. The preserved response to exogenous pulsatile GnRH localizes the defect upstream of the pituitary (pituitary is intact). Treatment: exogenous T/E2 for secondary sexual development; pulsatile GnRH or gonadotropin (hCG + FSH) for fertility.

B — Correct. Complete androgen insensitivity syndrome (CAIS) — X-linked loss-of-function in the AR. Testes produce T and AMH. AMH regresses Müllerian ducts (no uterus, blind vagina). T cannot signal through AR → Wolffian ducts regress, external genitalia default to female, pubic/axillary hair absent. Peripheral aromatization (in adipose/skin) converts the elevated T to E2 → ER signaling is intact → normal breast development at puberty. T negative feedback on the HPG axis is also impaired → ↑ LH (but FSH stays near-normal because inhibin B is intact from Sertoli cells). Management: gonadectomy after puberty (~2–5% lifetime gonadal malignancy risk) + estrogen replacement.

B — Correct. PCOS (Rotterdam: anovulation + hyperandrogenism + polycystic morphology) → chronic unopposed estrogen (adipose aromatization of androgens → E1) because anovulation means no corpus luteum and therefore no progesterone. Unopposed estrogen on the endometrium → simple → complex → atypical hyperplasia → Type I endometrial adenocarcinoma. Cyclic progestin (e.g., medroxyprogesterone 10 mg × 10–12 days/month) or OCPs are protective by inducing regular shedding of the endometrium. Metformin addresses insulin resistance; letrozole for ovulation induction when fertility is desired; spironolactone for hirsutism.

B — Correct. Premature ovarian insufficiency (POI) = menopause before age 40 (FSH >40 on two occasions ≥ 1 month apart + ↓E2 + amenorrhea). The family history (maternal uncle with intellectual disability, mother with early menopause) points toward Fragile X pre-mutation (FMR1) — the most common identifiable genetic cause of POI. Pre-mutation carriers (55–200 CGG repeats) have 20× risk of POI and male descendants are at risk for full Fragile X (>200 repeats) with intellectual disability. Management: systemic hormone replacement (estrogen + cyclic progestin if uterus intact) until the average age of natural menopause (~51) to protect bone density, cardiovascular health, and genitourinary tissue. Fertility via donor oocyte.