Clinical and hormonal effects of the combination gonadotrophin- releasing hormone agonist plus oral contraceptive pills containing ethinyl-oestradiol (EE) and cyproterone acetate (CPA) versus the EE-CPA pill alone on polycystic ovarian disease-related hyperandrogenisms
The aim of this study was to compare the clinical and hormonal effects of the combination of a long-acting gonadotrophin-releasing hormone analogue (GnRH-a) plus an oral contraceptive (OC) pill containing ethinyl-oestradiol (EE) and cyproterone acetate (CPA) versus the EE-CPA pill alone in patients with polycystic ovarian disease (PCOD) and related hyperandrogenisms, in order to evaluate whether the addition of GnRH-a has any advantage. A total of 12 PCOD patients were treated with the EE-CPA pill alone for 10 consecutive cycles according to an OC standard regimen. A further 12 patients were treated with GnRH-a, one i.m. injection every 28 days for a total of eight injections, combined with the EE-CPA pill for 10 consecutive cycles. The latter was thus prolonged for two cycles more than GnRH-a. Clinical evaluations (symptoms, weight, Ferriman-Gallwey score) and hormonal and biochemical analyses were assessed before, during (at 3 or 6 months) and after treatment, either when spontaneous cycles had resumed or after 3 months of amenorrhoea. There was a significant improvement in hirsutism, and a strong reduction in gonadotrophin, oestradiol, testosterone, androstenedione and 17-OH-progesterone concentrations in both treatment groups but with no significant differences between them, except in the gonadotrophin concentrations. Cortisol and triglyceride concentrations increased during treatment in both groups. The Ferriman-Gallwey score remained significantly decreased in both groups after treatment, as did androstenedione in the GnRH-a plus EE-CPA pill group, but there were no significant differences between the two groups. No changes were observed in prolactin, dehydroepiandrosterone sulphate (DHEA-S), insulin, glycaemia and cholesterol concentrations. However, when only the obese and more hirsute patients were considered, significant differences between the two groups were found during treatment in the Ferriman-Gallwey score and the gonadotrophin and DHEA-S concentrations (which increased during treatment in obese patients with the pill alone), and after treatment in the Ferriman-Gallwey score and the concentration of 17-OH-progesterone in the more hirsute patients, with the GnRH-a plus pill group having better results. In conclusion, a cyclic prolonged treatment with OC EE-CPA pills is not improved in most PCOD patients by the addition of GnRH-a, and is complicated and expensive. However, the addition of a long-acting GnRH-a may be recommended in obese and severely hirsute patients.