Letrozole and Cabergoline Versus Letrozole Alone in Ovulation Induction

In women with PCOS, the serum FSH levels are slightly lower during the follicular phase, therefore aromatization of excessive androgens is insufficient, and the follicles will not undergo the final FSH-dependent maturation in a dominant follicle. Furthermore, the serum level of anti-Mullerian hormone (AMH) is elevated. AMH counteracts the FSH-driven aromatase complex activity, so high AMH levels will inhibit granulosa cell conversion of androgens to estrogens and have a detrimental effect on final follicular maturation.

Previous studies showed that 30% of patients with PCOS show a modest rise in prolactin level. Increasing serum prolactin in these patients could be detected in both follicular and luteal phase of the normal and stimulated cycles. Dopamine release from the hypothalamus inhibits prolactin secretion, and it also affects the secretion of gonadotropins. When this inhibitory effect of dopamine is reduced, prolactin secretion will increase in addition to abnormalities in gonadotropins including luteinizing hormones.

Cabergoline which is a dopamine receptor agonist, with higher affinity to dopamine D2 receptors had improved uterine perfusion and achieved a better ovulatory response in PCOS patients, due to its ability to inhibit the vascular endothelial growth factor (VEGF) secretion in luteinized granulosa cells. Other studies concluded that Cabergoline use could normalize androgen level and therefore improve the menstrual irregularity in women with PCOS.

Letrozole is a third-generation aromatase inhibitor. It blocks the conversion of C-19 androgens to C-18 estrogens by competitively inhibiting the enzyme, aromatase (cytochrome P-450), which is an essential step in estrogen biosynthesis in the ovary and other tissues.The subsequent feedback to the hypothalamus containing reduced estrogen levels, triggers a compensatory increase in hypothalamic gonadotropin-releasing hormone (GnRH) secretion, and thus an increased release of pituitary gonadotropins FSH & LH. These gonadotropins subsequently promote growth of the follicles and stimulate ovulation. Letrozole has 99.9% bioavailability after oral administration. It has a single dose terminal half-life of 42 hours.

Inclusion criteria

• Women diagnosed with PCOS according to Rotterdam criteria (Rotterdam, 2004) as:

• Menstrual anomalies like amenorrhea (no cycles in the past 6 months), oligomenorrhoea (cycles lasting longer than 35 days), or long cycles.
• Clinical and/or biochemical hyperandrogenism.
• Ultrasound (USG) appearance of polycystic ovaries (multiple cysts >12 in number of 2-9 mm size).

Exclusion criteria

• Patient with liver and kidney disease.
• Congenital adrenal hyperplasia.
• Hypothalamic or pituitary cause of amenorrhea.
• Primary hyperprolactinemia.