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

M.F. Mitwally, Mohamed F M Mitwally, Lynda Gotlieb, Robert F Casper
Menopause (New York, N.Y.) · 2002 · vol. 9(4) , pp. 236–241 · doi:10.1097/00042192-200207000-00004 · PMID:12082359 · W1971380616
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This pilot study found that a low-dose estrogen and pulsed progestogen add-back regimen maintained bone mineral density and prevented symptom recurrence in long-term GnRH-agonist treated patients with endometriosis or PMS.

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Abstract

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. DESIGN: 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.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Bone Density Delayed-Action Preparations Endometriosis Estradiol Hormone Replacement Therapy Leuprolide Osteoporosis Premenstrual Syndrome Administration, Oral Adolescent Adult Bone Density Delayed-Action Preparations Densitometry Drug Administration Schedule Drug Therapy, Combination Endometriosis Endometriosis Estradiol Female

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