Induction of Ovulation With Raloxifene or Clomiphene Citrate in Polycystic Ovarian Syndrome

-Introduction The Polycystic Ovarian Syndrome (PCOS) is a frequent endocrine among women in reproductive ages, with a prevalence of 10%. In 2003, a consensus among the European and American Society of Human Reproduction (ESRHE and ASRM) defined that PCOS is a ovarian disfunction which present at least 2 out of 3 criteria: oligomenorrhea or anovulation; clinical or laboratorial signs of hyperandrogenism and polycystic ovaries on ultrasound; other causes, such as congenital adrenal hyperplasia, androgen secretory tumors, Cushing syndrome and hyperprolactinemia must be rule out.

Patients with PCOS who desire to became pregnant need, in their majority, induction of ovulation. Traditionally, clomiphene citrate, an estrogen receptor agonist, is the most used drug for this type of anovulation. The mechanism of action of clomiphene is related to a negative feedback to the endogenous estrogen, resulting in a higher amplitude of gonadotrophin surges, i.e., luteinizing hormone(LH) and follicle stimulating hormone(FSH). Nevertheless, recent studies have been shown that clomiphene citrate has a deleterious effect in the endometrium. The markers of uterine receptivity, among them, the integrin beta3 subunit, has its expression diminished, which implicate in a reduced fecundation rate.

The raloxifene is a selective estrogen receptor modulator. It has an agonist and antagonist activity over different organs. The daily therapy with raloxifene increase bone density, reduce cholesterol serum concentrations (LDL) and do not stimulate the endometrium in post-menopausal women (Delmas PD et al., 1997). Recent studies have shown that this drug is safe in healthy pre-menopausal women (Baker VL et al., 1998). A daily dosi of 100mg per 28 days, beginning on the 3rd day of the cycle, has shown that FSH and LH levels were not affected when compared to controls during the menstrual cycle. However, women who had received 100mg of raloxifene had a 31% increase in their FSH serum levels during the follicular phase, when compared to controls. An increase to 200mg did not increase FSH levels (Baker VL et al, 1998). Furthermore, it has been shown that raloxifene significantly increase the in vitro expression of αvβ3 integrin, suggesting a beneficial effect over the endometrium in relation to clomiphene (Lessey BA, personal communication, 2006).

-Objective To compare the ovulation rate between raloxifene and clomiphene among women with polycystic ovarian syndrome.

To identify the endometrial alterations compatible with ovulations, i.e., secretory endometrium, through endometrial biopsy between the women who used raloxifene or clomiphene.