Sequential estrogen-progestin addition to gonadotropin-releasing hormone agonist suppression for the chronic treatment of ovarian hyperandrogenism: a pilot study.

The purpose of the study was to evaluate the efficacy and safety of a sequential regimen of estrogen-progestin addition to GnRH agonist suppression in ovarian hyperandrogenism. Eight patients presenting with a polycystic ovary syndrome were treated with an sc implant of GnRH agonist every 4 weeks for 48 weeks. Starting at week 9, patients were replaced with 100 micrograms transdermal estradiol patches continuously and sequentially combined with 10 mg oral medroxyprogesterone acetate the last 2 weeks of each 4-week period. The rapid down-regulation of the pituitary-ovarian axis led to significant reduction of testosterone and androstenedione to 48.9% and 67.4% of baseline, respectively. During steroid replacement, testosterone and androstenedione continued to decrease gradually. The baseline hirsutism score (18.7 +/- 1.3) progressively fell to 9.7 +/- 2.0 at the end of treatment. The mean hair diameter was significantly reduced (0.097 +/- 0.004 vs. 0.081 +/- 0.005 mm). A withdrawal bleeding was obtained in 63.6% of the artificial cycles, but breakthrough bleeding occurred during 48% of the sequential replacements. The incidence of menopausal symptoms was low. There was a nonsignificant decrease in bone mineral content of the lumbar spine and the femoral neck but no trend in Ca2+/creatinine and OH-proline (OH-P)/creatinine ratios or in serum triglycerides and cholesterol fractions. There was a nonsignificant increase in hirsutism score in five patients followed up for 24 weeks after cessation of treatment, although there was a rapid return of hormones toward baseline and recurrence of irregular bleeding. Transdermal estradiol addition periodically combined with medroxyprogesterone acetate is effective in reducing hirsutism and is safe in minimizing side effects and bone loss. A regimen allowing a better bleeding control would make this approach a valuable alternative for prolonged or repeated palliative treatment of excessive hair growth and irregular bleeding in polycystic ovary syndrome.