Clomiphene versus Clomiphene plus Tamoxifen in Ovulation Induction in Women with PCOS: Randomized Controlled Trial

Abstract

Polycystic ovary syndrome is one of the most common endocrine disorders in women of reproductive age and metabolic disorder in which patients will benefit for early recognition and treatment. The prevalence of PCOS varies between 5% and 10% of all women. Polycystic ovary syndrome is clinically characterized by chronic anovulation, menstrual irregularities, infertility and obesity in combination with some evidence of androgen excess such as hirsutism, acne and increased serum androgen concentrations. The fundamental pathophysiologic defect still remains unknown. PCOS appears to be a heterogeneous disorder in which ovarian, and possibly adrenal androgen excess is present along with varying degrees of gonadotropic and metabolic abnormalities. Additionally insulin resistance, hyperinsulinism, type II Diabetes Mellitus, endometrial carcinoma, dyslipidemia and psychosocial dysfunction are presented as other clinical consequences associated with PCOS. Clomiphene citrate (CC) is the traditional first-line treatment for the chronic anovulation that characterizes PCOS. In addition, clinical data revealed a discrepancy in ovulation rates and conception rates During CC treatment. A longer clomiphene citrate free time during the sensitive peri-implantation period seems more promising than the traditional regimen as treatment with clomiphene citrate is associated with higher rates of pregnancy if started early in the menstrual cycle. Tamoxifen is an antagonist of the estrogen receptor as it competitively binds to estrogen receptors on the tissue targets, producing a nuclear complex that decreases DNA synthesis and inhibits estrogen effects. It is a nonsteroidal agent with potent antiestrogenic properties which compete with estrogen for binding sites in the tissues. Tamoxifen causes cells to remain in the G0 and G1 phases of the cell cycle. Tamoxifen is cytostatic rather than cytocidal. Tamoxifen itself is a pro-drug, having relatively little affinity for its target protein, the estrogen receptor. It is metabolized in the liver by the cytochrome P450 isoform CYP2D6 and CYP3A4 into active metabolites such as 4-hydroxytamoxifen and N-desmethyl-4-hydroxytamoxifen (endoxifen) which have 30-100 times more affinity with the estrogen receptor than tamoxifen itself. These active metabolites compete with estrogen in the body for binding to the estrogen receptor. Tamoxifen is used to treat infertility in women with anovulatory disorders. A dose of 10–40 mg per day is administered in days 3–7 of a woman's cycle. The aim of the study was to investigate the efficacy of two drug treatment regimens: clomiphene and a combination of clomiphene and tamoxifen in treating infertile women with PCO. This study included 100 patients of those attending the infertility clinic Armed forces Hospital in Alex suffering from PCOS during the period from January 2012 to march 2013. All patients was diagnosed as PCOS according to Rotterdam criteria (Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, 2003):- 1- Primary infertility. 2- Age 20:35 years old. 3- Normal semen analysis. 4- Normal H.S.G (hystrosalpingogram). 5- No medical disease. 6- Diangnostic criteria of PCO by Rotterdam consensus. 1. Menstrual irregularities: oligomenorrhea and/or amenorrhea. - Oligomenorrhea (menses that occur at intervals greater than 35 days). - Amenorrhea (absence of menstruation for more than 6 monthes). 2. Excess androgen activity. - Clinically: hirsutism. - Biochemically: elevated single serum androgen. 3. Polycystic ovaries (by gynecologic ultrasound).