Reproductive physiology

The ovary: two cells, two gonadotrophins

• FSH alone grows follicles, but oestradiol stays low without LH, because theca cells must supply androgen substrate.
• Oocytes: about 7 million at mid-gestation, 300,000–400,000 at menarche; most undergo atresia. Menopause (average about 50) is natural exhaustion of follicles: FSH and LH rise. Fertility falls from the mid-30s mainly because the remaining oocytes are of poorer quality with more meiotic errors (aneuploidy), not because cycles stop.
• Sex steroids act on intracellular (nuclear) receptors that change gene transcription.

Feedback

• Low oestradiol exerts negative feedback. Oestradiol that stays high for about 2 days switches to positive feedback: the LH surge (roughly a tenfold rise). So peak oestradiol with no progesterone means ovulation is about to occur.
• In the first years after menarche positive feedback is immature: cycles are anovulatory and irregular.
• Progesterone slows GnRH pulses in the luteal phase.
• Falling inhibin B gives an early follicular FSH rise in the late 40s. FSH is measured on day 2–3. AMH reflects ovarian reserve on any day.

Timing the cycle

• The luteal phase is fixed at about 14 days, so ovulation day = cycle length − 14: 28 days, day 14; 24 days, day 10; 21–23 days, about days 7–9; 32 days, day 18; 35 days, day 21. Couples are advised to have intercourse in the few days before and on that day.
• LH rise begins 34–36 hours before ovulation. The oocyte released is a secondary oocyte arrested in metaphase II; meiosis I completes just before ovulation, and meiosis II only at fertilisation. The ovum survives about a day.
• Progesterone peaks about 7 days after ovulation: test on day 21 of a 28-day cycle, day 25 of a 32-day cycle. Basal body temperature rises 0.3–0.5 °C after ovulation.
• Follicle rupture needs prostaglandins and proteases. Daily NSAIDs (diclofenac) around mid-cycle can block rupture: the follicle luteinises without releasing the egg (luteinised unruptured follicle), seen as a persisting thick-walled cyst. A progesterone rise does not prove rupture.
• To delay menstruation (athlete, pilgrim), a progestogen (norethisterone) is given from a few days before the expected period; menses follow its withdrawal.

Endometrium, cervix and menstruation

• Oestrogen must come first because it induces progesterone receptors.
• Endometrial fibrinolysis keeps menstrual blood liquid; when flow is heavy it overwhelms this and small clots and tissue fragments pass, which is common and usually harmless. Heavy bleeding is loss above 80 mL.
• Day 25 biopsy with proliferative glands means anovulation (PCOS).

What the steroids do elsewhere

• Oestradiol is the most potent oestrogen; oestrone dominates after menopause (aromatase in fat); oestriol is the pregnancy oestrogen.
• Breathlessness in pregnancy: progesterone increases the respiratory centre's sensitivity to CO₂, so minute ventilation rises (mainly tidal volume) and PaCO₂ falls to about 4 kPa (30 mmHg), felt as dyspnoea.

Pregnancy, labour and lactation

• Placental progesterone comes from maternal cholesterol; oestriol needs fetal adrenal DHEA-S converted in fetal liver and placenta, so it reflects fetoplacental well-being.
• High placental steroids suppress FSH and LH; later in pregnancy the ovaries are quiet, with the corpus luteum regressed.
• Progestogen-only contraception lowers the total number of pregnancies but slows tubal motility and ciliary beating, so a higher proportion of failures are ectopic.
• Labour: functional progesterone withdrawal with a rising oestrogen to progesterone ratio; the Ferguson reflex amplifies oxytocin.
• Lactation needs prolactin; placental steroids block milk secretion until delivery. Sheehan syndrome (pituitary infarction after massive PPH) causes failure to lactate from loss of prolactin; MRI later shows a small pituitary in an empty sella.

Male reproductive physiology

• Leydig cells: LH drives testosterone synthesis. In fetal life placental hCG drives them first.
• Sertoli cells: FSH drives androgen-binding protein, inhibin B and germ cell support; tight junctions form the blood–testis barrier.
• Spermatogenesis takes about 64–74 days at 2–3 °C below core.
• Exogenous testosterone suppresses LH, so intratesticular testosterone falls: small testes, azoospermia.
• 5α-reductase makes DHT for external genitalia, prostate and hair follicles; testosterone drives Wolffian ducts and muscle. Many testosterone actions depend on conversion to DHT or to oestradiol (bone, growth plate closure).
• Semen: seminal vesicles give most of the volume, fructose and alkalinity; prostate gives acid phosphatase, PSA and citrate. Low-volume, acidic, fructose-negative azoospermia means absent seminal vesicles or ejaculatory duct obstruction (congenital absence of the vas with CFTR mutations).

Disorders of sex development

• Ovotesticular DSD (true hermaphroditism): both ovarian follicles and seminiferous tubules (ovotestis); the commonest karyotype is 46,XX, often with SRY translocation or mosaicism.
• Androgen insensitivity (46,XY): testes, female external genitalia, breasts by aromatisation, no uterus, LH high.
• Congenital adrenal hyperplasia (46,XX): virilisation with normal ovaries and uterus.

Imaging correlation

• Dominant follicle ruptures at 18–25 mm; then free fluid in the pouch of Douglas.
• Corpus luteum: thick-walled cyst with a ring of peripheral colour flow because its wall has rich new vessels (LH-driven angiogenesis supplies steroid substrate). Do not mistake it for an ectopic or tumour.
• PCOS: enlarged ovaries with 20 or more peripheral 2–9 mm follicles and dense stroma.
• An intrauterine sac should be visible above a β-hCG of about 1500–3500 IU/L.
• BRCA1 and BRCA2 should be tested when relatives have early breast cancer and ovarian cancer. Ovarian carcinoma spreads mainly transcoelomically across the peritoneum (malignant ascites, omental cake).

Remember Count back 14 days from the next period to find ovulation, and forward 7 days from ovulation to find peak progesterone.

Exam trap Ovulation is not always on day 14: only the luteal phase is fixed.

Exam trap Progestogen-only methods reduce pregnancies overall but raise the share that are ectopic.

How FCPS asks about this

• Ovulation in a 24-day cycle: day 10 (cycle length minus 14).
• Peak oestradiol, no progesterone for 3 days: LH surge and ovulation are imminent.
• Source of oestrogen and progesterone after the first trimester: placenta; before 10 weeks, corpus luteum.
• Follicle fails to rupture on NSAIDs: inhibited follicular prostaglandin synthesis.
• Ring of Doppler flow around an ovarian cyst on day 22: vascular wall of the corpus luteum.
• Fructose-negative, acidic, low-volume semen: absent seminal vesicles.
• Ovotestis karyotype: most commonly 46,XX.