Effect of gonadotropin-releasing hormone agonist on the bone mineral density of patients with endometriosis

Dienogest is as effective as intranasal buserelin acetate for the relief of pain symptoms associated with endometriosis—a randomized, double-blind, multicenter, controlled trial

“…Exclusion criteria were as follows: [1] undiagnosed genital bleeding; [2] class 3 or more on Pap test within 3 months before enrollment; [3] use of GnRH agonists, testosterone derivatives, hormonal therapy with progesterone and/or estrogen, estrogen antagonists, or aromatase inhibitors within 16 weeks before enrollment; [4] pregnant or nursing; [5] a history of severe adverse drug reactions or hypersensitivity to steroid hormone or GnRH agonists; [6] past use of GnRH agonists with low BMD (<80% of the young adult mean); [7] having undergone surgery therapy or surgical examination for endometriosis within a menstrual cycle before the start of medication; [8] use of drugs that could be expected to affect the release of sex hormones (e.g., sulpiride, cimetidine); [9] a history or complication of thrombosis/embolism or depression; [10] malignant tumor complication or findings suggestive of a malignant tumor; [11] complication of serious heart, liver, kidney, blood, or endocrine disease; [12] participation in another clinical trial within the 4 months before enrollment; or [13] patients deemed unsuitable for study entry by the investigator.…”

“…The BMD of the lumbar spine (L2-L4) was measured by dual-energy roentgogram absorptiometry (DXA) with QDR-1000, QDR-1000 plus, QDR-2000, or QDR-4500 (Hologic Inc., Bedford, MA) at baseline and at the end of treatment in the subgroup composed of all the patients enrolled in the limited study centers. Based on the existing results (13,14), we expected that DNG would cause less bone loss than BA by 3.4% AE 3.6%, and thus we planned 60 patients would be measured; that is, 30 patients in each treatment group, for comparison of BMD to detect the difference statistically under a power of 90% with a two-sided significance level of 5%. The BMD measurement procedures were performed under double-blind conditions and the results were confirmed through reanalysis by the third-party experts for bone analysis who were blinded on the information of patients and study centers.…”

Maternal Mineral and Bone Metabolism During Pregnancy, Lactation, and Post-Weaning Recovery

“…However, its effects differ from what is observed during lactation (TABLE 3). Six months of acute estradiol deficiency causes 2-4% reductions in BMD of the spine with no losses at cortical sites (288,415,640,657,684,696,758,762,781,891,942). This is accompanied by increased serum calcium and phosphorus (265,288,640,657,781), increased fractional excretion of calcium (265,288,640,657,781,891,942), and low PTH and calcitriol (265,657,781).…”

“…Estradiol suppresses bone formation and resorption when administered as replacement therapy in peri-and postmenopausal women (305,750); it is not a potent stimulator of bone formation. Moreover, when reproductive-age women experience temporary estradiol deficiency induced by GnRH analog treatment, they lose a small amount of BMD and (unlike after lactation) most do not restore it afterwards (288,415,640,657,684,696,758,762,781,891,942). Earlier resumption of menses has correlated with an earlier apparent increase in bone mass after lactation (484,764), which suggests a benefit of higher estradiol.…”

Premenopausal bone health assessment

“…Tamoxifen, which can prevent bone loss in postmenopausal women, is associated with bone loss in premenopausal women [41]. Premenopausal women treated for endometriosis with gonadotropin releasing hormone (GnRH) agonists, such as leuprolide, may lose BMD [42]. Bone effects of GnRH agonists are of particular concern in young women who have not yet attained peak bone mass [43].…”