Hum. Reprod. Advance Access originally published online on April 22, 2004
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Human Reproduction, Vol. 19, No. 6, 1465-1471,
June 2004
© 2004 European Society of Human Reproduction and Embryology
One year comparison between two add-back therapies in patients treated with a GnRH agonist for symptomatic endometriosis: a randomized double-blind trial
1 Service de Gynécologie-Obstétrique, Hôpital Antoine Béclère, AP-HP, 92141 Clamart, 2 Laboratoires Takeda, 92816 Puteaux, 3 Service de Gynécologie-Obstétrique, Hôpital Universitaire Arnaud de Villeneuve, 34295 Montpellier, 4 Beaumont Clinic, 63110 Beaumont, 5 Service de Gynécologie-Obstétrique, Hôpital Jean Rostand, 92311 Sèvres and 6 Service de Rhumatologie, Hôpital Cochin, Université René-Descartes, 75014 Paris, France
7 To whom correspondence should be addressed. e-mail: herve.fernandez{at}abc.ap-hop-paris.fr
BACKGROUND: It has been proposed that hormonal supplementation during prolonged GnRH agonist therapy prevents hypoestrogenic side effects, including bone loss. The optimal combination for long-term treatments with safe metabolic profile remains questionable. A norprogesterone derivative, promegestone, was assessed for the first time in a double-blind trial. METHODS: Seventy-eight patients with endometriosis with rAFS (Revised American Society for Reproductive Medicine) scores of III–IV were randomly assigned to monthly leuprorelin 3.75 mg (1 year) which, after the third injection was used in combination with promegestone 0.5 mg (P) plus either estradiol placebo (PL) or estradiol 2 mg (E) per day. Bone mineral density (BMD) was determined at baseline, 6 and 12 months, and biological and clinical quarterly assessments were performed. Analysis was by the intention to treat method. RESULTS: At month 12, BMD changes from baseline were –6.1 ± 3.7 and –4.9 ± 4.0% in the PL-P group, at the spine and hip, respectively. This bone loss was prevented in the E-P group: –1.9 ± 3.1 and –1.4 ± 2.3%, respectively (P < 0.0001 inter-group comparisons). The BMD decrease in the E-P group was explained by the changes occurring during the first 6 months of treatment. There was no deleterious change in lipid parameters. Clinical improvement was observed without an inter-group difference. CONCLUSIONS: Estradiol 2 mg and promegestone 0.5 mg per day is an effective and safe add-back therapy, which can be proposed for prolonged leuprorelin treatment over 6 months in severe endometriosis.
Key words: add-back therapy/bone mineral density/endometriosis/GnRH agonists/leuprorelin