Long-term medical therapy for leiomyomata uteri: a prospective, randomized study of leuprolide acetate depot plus either oestrogen-progestin or progestin 'add-back' for 2 years.
Treatment of women with leiomyomata with gonadotrophin-releasing hormone agonists (GnRHa) for > 6 months is not recommended because of concerns regarding adverse sequelae of prolonged hypoestrogenism. It has been postulated that addition of low-dose sex steroids to GnRHa treatment, i.e. 'add-back' therapy, may avert some of these adverse effects (accelerated bone resorption, vasomotor flushes) without altering the efficacy of GnRHa therapy. To evaluate the effects of long-term GnRHa therapy on uterine size, bleeding patterns, bone mass and lipids, 51 pre-menopausal women with leiomyomata were treated with the GnRHa leuprolide acetate depot, 3.75 mg every 4 weeks for 2 years. After 3 months of leuprolide therapy, the women were randomized to receive either low-dose continuous oestropipate, 0.75 mg daily, plus cyclic norethindrone, 0.7 mg on days 1-14 each month (the oestrogen-progestin add-back group) or higher-dose norethindrone, 10 mg daily (the progestin add-back group), for the remaining 21 months. Mean uterine volume decreased by 40% in both treatment groups during the first 3 months on leuprolide treatment. There was no significant change in uterine size following oestrogen-progestin add-back. However, mean uterine volume in the progestin add-back group increased to 87% of pre-treatment size by treatment month 12 and 95% of pre-treatment size by treatment month 24. Mean bone density of the lumbar spine as measured by dual X-ray absorptiometry decreased significantly by 2.6% during the first 3 months in all patients, but did not change significantly following steroid add-back in both treatment groups during the final 21 treatment months.(ABSTRACT TRUNCATED AT 250 WORDS)
Friedman
A J
AJ
Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Daly
M
M
Juneau-Norcross
M
M
Gleason
R
R
Rein
M S
MS
LeBoff
M
M
D000328:Adult; D015519:Bone Density / Q000187:drug effects; D008076:Cholesterol, HDL / Q000097:blood; D003692:Delayed-Action Preparations; D045166:Estradiol Congeners / Q000008:administration & dosage; D004970:Estrone / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006400:Hematocrit; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016729:Leuprolide / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage; D011446:Prospective Studies; D013997:Time Factors; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D008076:Cholesterol, HDL; D003692:Delayed-Action Preparations; D045166:Estradiol Congeners; D004970:Estrone; D016729:Leuprolide; C009927:estropipate; D009640:Norethindrone