PH7.9 | PH7.9 | Infertility Pharmacotherapy — SDL Guide — Summary & Reflection

KEY TAKEAWAYS

Infertility Pharmacotherapy — Key Takeaways:

• Clomiphene citrate: SERM — blocks oestrogen negative feedback at hypothalamus/pituitary → ↑FSH/LH → ovulation. Days 3–7, 50–150 mg. Anti-oestrogenic endometrial effect (disadvantage vs letrozole).
• Letrozole: Aromatase inhibitor — ↓ peripheral oestrogen → ↑FSH centrally. Short half-life (no endometrial anti-oestrogenic effect). First-line for PCOS per PCOSACT trial (higher live birth rate than clomiphene).
• PCOS ladder: Lifestyle/metformin → letrozole → clomiphene → gonadotropins → ART.
• Hyperprolactinaemia anovulation: Cabergoline (dopamine agonist) — restores prolactin to normal → GnRH pulsatility → spontaneous ovulation; usually no additional ovulation inducer needed.
• OHSS (Ovarian Hyperstimulation Syndrome): Most serious with gonadotropins; also clomiphene. Severe = ascites, pleural effusion, thromboembolism. Prevention: ultrasound monitoring, low-dose start, withhold hCG trigger, use GnRH agonist trigger, cabergoline prophylaxis.
• Male infertility and testosterone TRAP: Exogenous testosterone → HPG suppression → ↓LH → ↓intratesticular T → impairs spermatogenesis. NEVER prescribe testosterone for male infertility. Use hCG (LH-like) + rFSH for hypogonadotropic male infertility.
• Metformin in PCOS: Corrects insulin resistance → reduces ovarian androgen → may restore ovulation; use as adjunct, not primary ovulation inducer.

REFLECT

The PCOS pharmacological algorithm has evolved rapidly: letrozole (an aromatase inhibitor originally developed for breast cancer) is now the preferred ovulation inducer in PCOS based on a single landmark trial. Reflect on this pharmacological translation: (1) what is the mechanistic reason aromatase inhibition helps PCOS (hint: think about where the excess oestrogen in PCOS comes from, and how reducing it centrally frees up FSH); (2) why was letrozole initially considered 'off-label' for infertility (original approval was for breast cancer); (3) what does this tell you about how pharmacological evidence evolves — and why 'off-label' does not mean 'unsafe' if the evidence base is strong? Write three sentences connecting the pharmacological mechanism, the clinical trial, and the regulatory/evidence framework.