Prevention of bone loss and hypoestrogenic symptoms by estrogen and interrupted progestogen add-back in long-term GnRH-agonist down-regulated patients with endometriosis and premenstrual syndrome.
OBJECTIVE
To examine the utility of a low-dose estrogen and pulsed progestogen hormone replacement therapy (HRT) regimen for add-back during long-term gonadotropin-releasing hormone-agonist (GnRH-agonist) therapy.


METHODS
A pilot clinical trial conducted at a tertiary referral, academic, reproductive sciences center. The study included 15 patients with endometriosis and 5 patients with severe premenstrual syndrome (PMS). Patients with endometriosis received leuprolide acetate depot 3.75 mg IM monthly until their symptoms had resolved (2-3 months), at which time HRT was initiated along with the GnRH-agonist. Patients with severe PMS received the same treatment with the addition of HRT after 1 month. The HRT regimen consisted of 1 mg oral micronized estradiol daily and 0.35 mg norethindrone daily for 2 days alternating with 2 days without norethindrone. The main outcome measure included bone density assessment in the lumbar spine and femoral neck by dual-energy x-ray absorptiometry at 6- to 12-month intervals. The mean follow-up duration +/- SD while on GnRH-agonist treatment was 31.2 +/- 17 months (for endometriosis patients) and 37.7 +/- 8.4 months (for patients with severe PMS).


RESULTS
Bone mineral density was stable after initiation of HRT for the entire follow-up period. No patient had return of pelvic pain or resumption of mood swings after HRT add-back. After the first 3 months of HRT, all women remained amenorrheic.


CONCLUSIONS
Long-term GnRH-agonist down-regulation is safe and effective when combined with HRT add-back. Furthermore, on the basis of this small study, the low-dose pulsed progestogen, continuous estrogen HRT regimen seems to be safe for use as add-back therapy in terms of bone health.
Mitwally
Mohamed F M
MF
Division of Reproductive Sciences, Department of Obstetrics and Gynecology, Samuel Lunenfeld Research Institute and Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Gotlieb
Lynda
L
Casper
Robert F
RF
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D015519:Bone Density / Q000187:drug effects*; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D003720:Densitometry; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004715:Endometriosis / Q000175:diagnosis / Q000188:drug therapy*; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage*; D008875:Middle Aged; D010024:Osteoporosis / Q000517:prevention & control*; D010865:Pilot Projects; D011293:Premenstrual Syndrome / Q000175:diagnosis / Q000188:drug therapy*; D012016:Reference Values; D012720:Severity of Illness Index; D016896:Treatment Outcome
D003692:Delayed-Action Preparations; D004958:Estradiol; D016729:Leuprolide