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 supp ression in ovarian hyperandrogenism. Eight patients presenting with a polycystic ovary syndrome were treated with an sc implant of GnRH agon ist every 4 weeks for 48 weeks. Starting at week 9, patients were repl aced with 100 mu g transdermal estradiol patches continuously and sequ entially combined with 10 mg oral medroxyprogesterone acetate the last 2 weeks of each 4-week period. The rapid down-regulation of the pitui tary-ovarian axis led to significant reduction of testosterone and and rostenedione to 48.9% and 67.4% of baseline, respectively. During ster oid replacement, testosterone and androstenedione continued to decreas e 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 w as significantly reduced (0.097 +/- 0.004 vs. 0.081 +/- 0.005 mm). A w ithdrawal bleeding was obtained in 63.6% of the artificial cycles, but breakthrough bleeding occurred during 48% of the sequential replaceme nts. The incidence of menopausal symptoms was low. There was a nonsign ificant decrease in bone mineral content of the lumbar spine and the f emoral neck but no trend in Ca2+/creatinine and OH-proline (OH-P)/crea tinine ratios or in serum triglycerides and cholesterol fractions. The re was a nonsignificant increase in hirsutism score in five patients f ollowed up for 24 weeks after cessation of treatment, although there w as a rapid return of hormones toward baseline and recurrence of irregu lar bleeding. Transdermal estradiol addition periodically combined wit h medroxyprogesterone acetate is effective in reducing hirsutism and i s safe in minimizing side effects and bone loss. A regimen allowing a better bleeding control would make this approach a valuable alternativ e for prolonged or repeated palliative treatment of excessive hair gro wth and irregular bleeding in polycystic ovary syndrome.