Pituitary function is altered during the same cycle in women with polycystic ovary syndrome treated with continuous or cyclic oral contraceptives or a gonadotropin-releasing hormone agonist

Abstract

Objective: To determine if continuous oral contraceptive (OC) therapy was superior to a cyclic regimen in achieving persistent pituitary suppression of LH in patients with polycystic ovary syndrome (PCOS).

Design: Fourteen women (ages 16 to 41 years) with PCOS received one of three treatment groups: continuous OC therapy (30 micrograms ethinyl E2 plus 150 micrograms desogestrel), cyclic OC therapy, or monthly injections of a GnRH agonist (GnRH-a, leuprolide acetate depot 3.75 mg) for 3 months. Basal hormone levels were obtained before initiating therapy, on days 15 to 17 of the 3rd month of treatment (study 1) and again on days 26 to 28 of the 3rd month (study 2). A GnRH stimulation test was also performed during study 1 and study 2.

Results: After 3 months of treatment, LH levels were decreased significantly in all groups with less effective suppression observed in the cyclic OC group compared with the continuous OC or GnRH-a groups. A significant rise in LH was found only in the cyclic OC group after 5 to 7 days of placebo treatment (study 1 versus study 2). An increase in T was also observed in the cyclic OC group during study 2, whereas the continuous OC and GnRH-a groups showed continued inhibition of T levels. Although there was no significant difference in LH area under the curve (AUC) measurements after GnRH stimulation in study 1 versus study 2, the LH AUC was significantly greater in both studies in the cyclic OC group compared with the continuous OC or GnRH-a groups.

Conclusions: Increased LH secretion during the week of placebo in the cyclic OC group was associated with a concomitant increase in T. The striking rise in LH secretion after GnRH stimulation in the cyclic OC group may represent increased pituitary sensitivity in patients receiving cyclic OCs regardless of the phase of the treatment cycle, perhaps secondary to increased pituitary stores of LH in these women.

PIP: Clinical researchers recruited 16 women aged 16-41 diagnosed with polycystic ovary syndrome (PCOS) for a study designed to compare their pituitary responsiveness to exogenous gonadotropin releasing hormone (GnRH) stimulation after three months of therapy with either the continuous or cyclic regimen of combined oral contraceptives (OCs). The three treatments included six women on continuous therapy (i.e., every day for 3 months) with an OC containing 30 mcg ethinyl estradiol and 150 mcg desogestrel, six women on cyclic therapy (i.e., 21 days of OC therapy with 7 days of placebo over 3 months) with the same OC formulation, and four women on therapy with a GnRH agonist (GnRH-a), Lupron depot (3.75 mg leuprolide acetate). Luteinizing hormone (LH) levels fell significantly in all groups between baseline and three months treatment (p 0.001). Cyclic OCs exerted a less effective LH suppression than the continuous OC and the GnRH-a, however (88% vs. 99%; p 0.05). Only the cyclic OC group experienced a significant increase in LH after 5-7 days of placebo treatment (126% increase; p 0.008). The percent change in LH levels was significantly different between the cyclic and continuous OC groups (p 0.03) and between the cyclic OC and GnRH-a groups (p 0.01). Similarly, the cyclic OC group had an increase in testosterone levels after 5-7 days of placebo treatment (86% increase), while the other two groups had no change. When both the cyclic and continuous OC groups received their first GnRH stimulation test on days 15-17 of the third 28-day cycle and on days 26-28 (5-7 days of placebo in the OC cyclic group), the LH area under the curve (AUC) measurements were much greater in the cyclic OC group than the continuous OC and the GnRH-a groups (p 0.004). This event suggests increased pituitary sensitivity in patients receiving cyclic OCs regardless of the phase of the treatment cycle; which may be secondary to increased pituitary stores of LH in women with PCOS. These findings support the theory that LH contributes greatly to ovarian testosterone secretion in women with PCOS.