Hormonal therapies for endometriosis: implications for bone metabolism

The non-surgical treatment of endometriosis involves hormone therapy that either affects the lesions directly, or indirectly inhibits endometrial proliferation and induces atrophy through estrogen deprivation, or through a combination of these effects. The medications used to treat endometriosis are progestins (e.g. norethindrone, medroxyprogesterone acetate), oral contraceptives (e.g. estrogen-progesterone acetate), androgens and their derivatives (e.g. danazol, gestrinone), and gonadotropin-releasing hormone (GnRH) agonists (e.g. buserelin, leuprolide acetate, nafarelin, goserelin, tryptorelin). Agents such as GnRH agonists that produce sustained and prolonged hypoestrogenemia, similar to the postmenopausal hypogonadal state, can have a significant negative impact on trabecular bone mass. Evidence from the use of oral contraceptives and medroxyprogesterone acetate indicated that they had no apparent adverse effect on bone mass. Initial studies with dual-photon absorptiometry were unable to detect any appreciable bone loss with GnRH agonists. Later studies, however, have invariably found significant bone loss as early as 3 months after the start of treatment. Quantitated computerized tomography always shows significant trabecular bone loss of the vertebrae and hip with GnRH agonists. Depot preparations appear to produce more marked loss than daily intranasal sprays. Recovery of bone loss may take 6-12 months after the end of therapy, with considerable individual variations. In contrast, treatment of endometriosis with danazol produces bone gain. If endometriosis has to be treated with bone-depleting agents, prevention or attenuation of bone loss using combined therapy with progestins, etidronate or calcitonin together with GnRH agonists should be considered; however, further studies are necessary to define the efficacy of such combined therapy. Smoking and excessive caffeine intake should be avoided. The risk of bone loss should be considered when choosing the appropriate management of endometriosis, the selection of patients, repeat therapies for recurrent endometriosis, and the formulation of such therapies, in order to minimize or overcome it.