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PY9.1-10 | Reproductive Physiology — Part 3
The Menstrual Cycle: A 28-Day Hormonal Symphony
The menstrual cycle is the recurring, hormonally-coordinated preparation of the female body for potential pregnancy. A typical cycle lasts 28 days (range 21–35 days). It has two parallel components:
Figure: The Menstrual Cycle: A 28-Day Hormonal Symphony
1. Ovarian cycle — what happens in the ovary:
• Follicular phase (Days 1–14): FSH stimulates growth of a cohort of follicles. One becomes dominant (the Graafian follicle). Granulosa cells produce increasing oestrogen.
• Ovulation (Day ≈14): Rising oestrogen → positive feedback → LH surge → rupture of the Graafian follicle → oocyte released into fallopian tube. The oocyte is in meiosis II (completes only if fertilised).
• Luteal phase (Days 14–28): Ruptured follicle becomes the corpus luteum (yellow body). Corpus luteum secretes progesterone (mainly) + oestrogen. If pregnancy does not occur, corpus luteum degenerates (~Day 26), progesterone falls, and menstruation begins.
2. Uterine cycle — what happens in the endometrium:
• Menstrual phase (Days 1–5): Progesterone withdrawal → prostaglandin-mediated vasoconstriction → ischaemia → shedding of the stratum functionalis (functional layer). Blood loss: 30–80 mL.
• Proliferative phase (Days 6–14): Rising oestrogen → endometrium rebuilds (3–5 mm → 8–10 mm). Glands straight, stroma sparse.
• Secretory phase (Days 15–28): Progesterone → endometrial glands coil and fill with glycogen. Stroma becomes oedematous. This is the "fertile" endometrium ready for implantation.
Hormonal timeline:
• Days 1–7: FSH rises → follicle grows → oestrogen rises slowly
• Days 8–12: Oestrogen rises sharply → positive feedback → LH surge (peaks Day 12–13)
• Day 14: LH surge → ovulation
• Days 15–26: LH falls; corpus luteum produces progesterone + oestrogen; FSH + LH suppressed
• Days 27–28: Corpus luteum degenerates → progesterone + oestrogen fall → FSH begins to rise → new cycle begins
Anovulatory cycles (cycles without ovulation): Common at extremes of reproductive life (early post-menarche, perimenopause) and in conditions like polycystic ovary syndrome (PCOS). The luteal phase and progesterone production are absent.
CLINICAL PEARL
PCOS — A Common Cause of Irregular Periods:
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age (6–10% prevalence). Key features: oligomenorrhoea or amenorrhoea (irregular or absent periods), hyperandrogenism (acne, hirsutism), and multiple small ovarian follicles on ultrasound.
Pathophysiology: Elevated LH:FSH ratio → excess androgen from theca cells → follicles fail to mature → no dominant follicle → no ovulation → no corpus luteum → no progesterone → prolonged oestrogen effect → irregular bleeding.
Clinical relevance: PCOS is a common cause of anovulatory infertility. Insulin resistance and metabolic syndrome are closely associated. Clomiphene (anti-oestrogen → removes negative feedback → raises FSH) is first-line treatment for ovulation induction.
SELF-CHECK — Part 3 Self-Check
On Day 13 of the menstrual cycle, oestrogen levels peak. What happens next?
A. Negative feedback — FSH and LH fall
B. Positive feedback — LH surges, triggering ovulation
C. Progesterone rises, inhibiting ovulation
D. GnRH release is suppressed
Reveal Answer
Answer: B. Positive feedback — LH surges, triggering ovulation
A woman's basal body temperature rises by 0.5°C on Day 15 of her cycle. This is due to:
A. Rising oestrogen from the Graafian follicle
B. LH surge
C. Progesterone secreted by the corpus luteum
D. FSH-driven follicular growth
Reveal Answer
Answer: C. Progesterone secreted by the corpus luteum
Contraception: Physiology Turned into Prevention
Contraceptive Methods — Mechanism and Efficacy
| Method | Primary Mechanism | Efficacy (perfect use) | Key Advantage | Key Limitation |
|---|---|---|---|---|
| COCP | Suppresses ovulation (oestrogen + progestogen) | >99% | Regulates cycles, reduces dysmenorrhoea | DVT risk, requires daily compliance |
| Progesterone-only pill | Thickens cervical mucus | 91-99% | Safe in breastfeeding, no DVT risk | Must be taken at same time daily |
| DMPA injection | Suppresses ovulation + thick mucus | >99% | 3-monthly, no daily compliance | Weight gain, delayed return of fertility |
| Copper IUD | Spermicidal + inflammatory reaction | >99% | Non-hormonal, 10-year duration, emergency contraception | Heavier periods, dysmenorrhoea |
| LNG-IUS (Mirena) | Thin endometrium + thick mucus | >99% | Reduces menstrual bleeding, 5-year duration | Irregular bleeding initially |
| Male condom | Physical barrier | 85-98% | STI protection | User-dependent efficacy |
| Vasectomy | Permanent sperm blockage | >99.9% | Permanent, very effective | Irreversible (reversal uncertain) |
Contraceptive Methods — Mechanism and Efficacy
Figure: Contraception: Physiology Turned into Prevention
| Method | Primary Mechanism | Efficacy (perfect use) | Key Advantage | Key Limitation |
|---|---|---|---|---|
| COCP | Suppresses ovulation (oestrogen + progestogen) | >99% | Regulates cycles, reduces dysmenorrhoea | DVT risk, requires daily compliance |
| Progesterone-only pill | Thickens cervical mucus | 91-99% | Safe in breastfeeding, no DVT risk | Must be taken at same time daily |
| DMPA injection | Suppresses ovulation + thick mucus | >99% | 3-monthly, no daily compliance | Weight gain, delayed return of fertility |
| Copper IUD | Spermicidal + inflammatory reaction | >99% | Non-hormonal, 10-year duration, emergency contraception | Heavier periods, dysmenorrhoea |
| LNG-IUS (Mirena) | Thin endometrium + thick mucus | >99% | Reduces menstrual bleeding, 5-year duration | Irregular bleeding initially |
| Male condom | Physical barrier | 85-98% | STI protection | User-dependent efficacy |
| Vasectomy | Permanent sperm blockage | >99.9% | Permanent, very effective | Irreversible (reversal uncertain) |
Contraceptive Methods — Mechanism and Efficacy
| Method | Primary Mechanism | Efficacy (perfect use) | Key Advantage | Key Limitation |
|---|---|---|---|---|
| COCP | Suppresses ovulation (oestrogen + progestogen) | >99% | Regulates cycles, reduces dysmenorrhoea | DVT risk, requires daily compliance |
| Progesterone-only pill | Thickens cervical mucus | 91-99% | Safe in breastfeeding, no DVT risk | Must be taken at same time daily |
| DMPA injection | Suppresses ovulation + thick mucus | >99% | 3-monthly, no daily compliance | Weight gain, delayed return of fertility |
| Copper IUD | Spermicidal + inflammatory reaction | >99% | Non-hormonal, 10-year duration, emergency contraception | Heavier periods, dysmenorrhoea |
| LNG-IUS (Mirena) | Thin endometrium + thick mucus | >99% | Reduces menstrual bleeding, 5-year duration | Irregular bleeding initially |
| Male condom | Physical barrier | 85-98% | STI protection | User-dependent efficacy |
| Vasectomy | Permanent sperm blockage | >99.9% | Permanent, very effective | Irreversible (reversal uncertain) |
Contraception means preventing fertilisation or implantation. Each method targets a specific step in the reproductive process. As a future doctor, you must know the mechanism, efficacy, side effects, and contraindications for each.
Figure: Contraception: Physiology Turned into Prevention
Combined Oral Contraceptive Pill (COCP) — "The Pill":
• Contains synthetic oestrogen (ethinylestradiol) + progestogen
• Mechanism: oestrogen + progestogen → constant negative feedback → suppresses GnRH → suppresses FSH + LH → no follicle development → no ovulation
• Additional effects: thick cervical mucus, thin atrophic endometrium (hostile to implantation)
• Efficacy: >99% with perfect use
• Side effects: nausea, breast tenderness, breakthrough bleeding, DVT risk (oestrogen raises clotting factors), hypertension
• Contraindications: migraine with aura, smoking >35 years, personal/family history of VTE, liver disease
Progestogen-only Pill (POP / "Mini-Pill"):
• Mechanism: primarily thickens cervical mucus (oestrogen-independent). May also inhibit ovulation (depends on dose/type).
• Safer in women who cannot take oestrogen (breastfeeding mothers, VTE risk, hypertension)
Intrauterine Device (IUD) — Copper:
• Non-hormonal. Copper ions are toxic to sperm (impair motility) and alter endometrium
• Also effective as emergency contraception (up to 5 days post-unprotected intercourse)
• Duration: 5–10 years. Side effect: heavier periods.
Intrauterine System (IUS) — Hormonal (e.g., Mirena):
• Releases levonorgestrel locally → thick cervical mucus, suppressed endometrium, may suppress ovulation
• Lighter periods (often used to treat heavy menstrual bleeding too)
Barrier methods:
• Male condom: physical barrier + STI protection. Efficacy 85–98% (typical vs. perfect use).
• Female condom: lines the vagina; also provides STI protection.
• Diaphragm/cervical cap: covers cervix; used with spermicide.
Male contraception:
• Vasectomy: surgical cutting/tying/sealing the vas deferens. Permanent. Very effective. Does not affect testosterone or libido (Leydig cells unaffected).
• Condoms: most common reversible method.
• Note: hormonal male contraception (testosterone injections) is under research but not yet approved.
Emergency contraception:
• Levonorgestrel (Plan B / i-Pill): taken within 72 hours. Delays or inhibits ovulation. Does not terminate an established pregnancy.
• Ulipristal acetate: effective up to 120 hours. Progesterone receptor modulator.
• Copper IUD: most effective (>99%) up to 5 days.
Physiology of Pregnancy
Fertilisation typically occurs in the ampulla of the fallopian tube, within 12–24 hours of ovulation. The fertilised egg (zygote) travels to the uterus over 3–4 days, undergoing cleavage divisions to become a morula, then a blastocyst.
Figure: Physiology of Pregnancy
Implantation occurs on Days 6–10 after fertilisation into the secretory endometrium. The outer layer of the blastocyst (trophoblast) invades the endometrium.
Human Chorionic Gonadotrophin (hCG):
• The trophoblast immediately begins secreting hCG — the "rescue signal" that keeps the corpus luteum alive past Day 26 (when it would normally degenerate).
• hCG has the same receptor as LH → corpus luteum continues producing progesterone → endometrium maintained → pregnancy established.
• hCG peaks at 8–10 weeks, then falls (the placenta takes over progesterone production from the corpus luteum by weeks 12–16).
• hCG is detectable in urine ≈10 days after conception → basis of pregnancy tests.
Placenta — the physiological interface between mother and fetus:
• Produces: oestrogen (from fetal DHEA-S), progesterone, hCG, hPL (human placental lactogen)
• hPL (human placental lactogen): anti-insulin effect → ensures glucose availability to fetus. Responsible for gestational diabetes in susceptible women.
• Allows: O₂, glucose, amino acids, IgG to cross to fetus
• Prevents: large molecules, maternal RBCs from crossing (normally)
Physiological changes of pregnancy:
• Cardiovascular: blood volume increases 40–50%; cardiac output increases 40%; heart rate rises 15 bpm; blood pressure falls in first/second trimester
• Respiratory: tidal volume increases 40%; respiratory rate unchanged; slight hyperventilation (progesterone-driven) → mild respiratory alkalosis → compensated by renal HCO₃⁻ excretion
• Renal: GFR increases 50%; serum creatinine and urea fall (so normal values appear lower in pregnancy). Glycosuria common (not necessarily diabetes).
• Haematological: plasma volume increases more than RBC mass → dilutional anaemia (physiological). WBCs increase (neutrophilia). Clotting factors increase → hypercoagulable state (VTE risk).
• GI: progesterone relaxes smooth muscle → constipation, GORD (heartburn), delayed gastric emptying.