The hypoestrogenic state induced by
gonadotropin-releasing hormone agonists (GnRHa) has been shown to suppress symptomatic
endometriosis effectively but to elicit vasomotor symptoms and loss of bone mineral density. The role of
norethindrone as a supplement to GnRHa in eliminating such side effects was assessed by enrolling 20 patients with symptomatic
endometriosis diagnosed laparoscopically in a randomized, prospective, double-blinded trial. All patients received the long-acting GnRHa
leuprolide acetate 3.75 mg im every 4 weeks for 24 weeks. Ten patients self-administered
norethindrone 5 then 10 mg by mouth daily, whereas the remainder self-administered placebo
tablets. Results of this study showed that combination
therapy was as effective as GnRHa alone in significantly reducing circulating
gonadotropin and
estrogen levels (P less than 0.01), extent of visible endometriotic implants (P less than 0.01), and painful symptoms (P less than 0.01). Marked vasomotor and vaginal symptoms experienced by patients given GnRHa alone were minimized in those receiving GnRHa with
norethindrone. Lumbar spine bone mineral density loss, measured by dual energy x-ray absorptiometry, was significantly reduced and more completely reversed in patients receiving combination
therapy (P less than 0.05). A reversible decrease in
high density lipoprotein-cholesterol and increase in
low density lipoprotein:
high density lipoprotein ratio was noted only in the patients receiving combination
therapy, but not in those receiving GnRHa only. The addition of
norethindrone to GnRHa is an effective means of treating symptomatic
endometriosis while ameliorating side effects induced by GnRHa alone.