A 32-year-old woman with PCOD and normal BMI (22 kg/m²) presents with amenorrhea and infertility for 2 years. Fasting insulin and HOMA-IR are normal. She has not ovulated on lifestyle modification alone. What is the drug of choice for ovulation induction?

Explanation

## Rationale for Clomiphene Citrate in Lean, Insulin-Sensitive PCOD **Key Point:** In lean PCOD (BMI <25) without insulin resistance (normal fasting insulin and HOMA-IR), clomiphene citrate is the first-line ovulation induction agent. **High-Yield:** Clomiphene is a selective estrogen receptor modulator (SERM) that blocks negative feedback of estrogen on the hypothalamus and pituitary, leading to increased GnRH and FSH secretion. It achieves ovulation in 70–80% of PCOD patients and pregnancy in ~40–50%. ### Mechanism of Clomiphene Citrate 1. Blocks estrogen receptors in hypothalamus and anterior pituitary 2. Removes negative feedback inhibition 3. Increases GnRH pulsatility and FSH secretion 4. Stimulates follicular growth and ovulation ### Comparison: Lean vs. Insulin-Resistant PCOD | Feature | Lean PCOD | Insulin-Resistant PCOD | |---------|-----------|------------------------| | **BMI** | <25 kg/m² | >30 kg/m² | | **Insulin Resistance** | Absent | Present | | **First-Line Drug** | Clomiphene citrate | Metformin | | **Mechanism** | Increases FSH | Improves insulin sensitivity | | **Ovulation Rate** | 70–80% | 30–40% (metformin alone) | | **Second-Line** | Letrozole / Gonadotropins | Clomiphene + metformin | **Clinical Pearl:** Clomiphene is ineffective in insulin-resistant PCOD because hyperinsulinemia suppresses SHBG and increases free androgens, counteracting the FSH stimulus. Metformin must be given first to restore insulin sensitivity. **Tip:** The normal BMI (22 kg/m²) and normal insulin levels are the key clinical clues that this is lean PCOD — clomiphene is appropriate as monotherapy. ### Dosing and Monitoring - **Starting dose:** 50 mg daily for 5 days (days 3–7 of cycle) - **Escalation:** Increase by 50 mg increments in successive cycles if no ovulation - **Maximum dose:** 150 mg daily - **Monitoring:** Transvaginal ultrasound to confirm ovulation; serum progesterone on day 21 [cite:Jeffcoate's Principles of Gynaecology Ch 14; ASRM Guidelines on PCOD]