Gonadotrophin-Releasing Hormone Analogues for Endometriosis: Bone Mineral Density

Summary

A Cochrane review [Abstract] 1 included 30 studies with a total of 2391 subjects, however only 15 trials involving 910 women could be included in the meta-analysis. There was a significantly bigger bone mineral density (BMD) loss of the lumbar spine in the gonadotrophin-releasing hormone analogues (GnRHa) only group compared with GnRHa + hormone replacement therapy (HRT: oestrogen + progesterone or oestrogen only) add-back after 6 months treatment (SMD -0.49, 95 % CI -0.77 to -0.21; 5 trials, n=219), and after 12 months treatment. However, by 24 months of follow-up there was no difference in BMD in those women who had HRT add-back. Between the groups receiving GnRHa and the groups receiving danazol/gestrinone, there was a significant difference in percentage change of BMD after 6 months of treatment, the GnRH analogue producing a reduction in BMD from baseline and danazol producing an increase in BMD (SMD -3.43, 95 % CI -3.91 to -2.95). Progesterone only add-back is not protective; after 6 months of treatment absolute value BMD measurements of the lumbar spine did not differ significantly from the group receiving GnRHa (SMD 0.15, 95 % CI -0.21 to 0.52). Studies of danazol versus GnRHa did not report long-term follow-up. There are inconclusive data about calcium-regulating agents. No difference was found between low and high dose add-back regimes but again only one study was identified for this comparison. Only one study comparing GnRH analogues with placebo was identified, but the study gave no data. No studies comparing GnRH with the oral contraceptive pill or progestagens were identified.

A study 2 compared the efficacy and tolerability of GnRH agonist with add-back therapy (7β-estradiol and norethisterone acetate) versus dienogest for preventing pelvic pain recurrence after laparoscopic surgery in women with enodmetriosis (n=64). Visual analogue scale pain score decreased significantly for both treatments with no significant differences between groups. Neither physical, psychological, social, and environmental components of quality-of-life nor menopausal rating scale score were significantly different between the two groups. Bone mineral density at the lumbar spine declined significantly in both treatment groups (-2.5 % for GnRH agonist plus add-back and -2.3 % for dienogest), with no significant difference between the two groups.