Young women with hypothalamic amenorrhea and oligomenorrhea are likely to have reduced bone mineral density and are at greater risk of osteoporosis. Estrogen replacement therapy is known to reduce the risk of osteoporotic fractures in postmenopausal women. Hergenroeder and associates performed a randomized, controlled clinical trial comparing treatment with oral contraceptives, medroxyprogesterone acetate and placebo to determine which therapy might improve bone mineral density in young women with hypothalamic dysfunction.

A total of 24 white women ranging from 14 to 28 years of age with hypothalamic amenorrhea or oligomenorrhea were prospectively randomized to a 12-month regimen of either oral contraceptive pills, medroxyprogesterone or placebo if they were amenorrheic, or medroxyprogesterone or placebo if they were oligomenorrheic. Bone mineral density was measured by dual-energy x-ray absorptiometry at baseline and at six months and 12 months following therapy. Patients in the oral contraceptive group received 0.035 mg of ethinyl estradiol and 0.5 to 1.0 mg of norethindrone per day for 21 days of the 28-day cycle. Patients in the medroxyprogesterone group received 10 mg per day on the last 12 days of the calendar month. Those in the placebo group received one tablet per day on the same days as the medroxyprogesterone group.

The 15 women in the amenorrheic group had a lower mean baseline percentage body fat, compared with the nine women in the oligomenorrheic group. Total body mineral content and bone density of the amenorrheic group at 12 months were greater in the oral contraceptive group than in the medroxyprogesterone and placebo groups. At six and 12 months, no significant differences in the bone mineral content or density at any site were found between the medroxyprogesterone and placebo groups. In the patients with oligomenorrhea, total body bone mineral content at 12 months was greater in the placebo group than in the medroxyprogesterone group.

The changes in and the absolute measurements of bone mineral density and content at all bone sites were independent of weight change during the study. After adjusting for age, body weight and baseline measurements, treatment with oral contraceptives was associated with improved lumbar spine, total body bone mineral content and bone mineral density at 12 months in young women with hypothalamic amenorrhea. There was no apparent improvement of the bone mineral of the femoral neck in these women. Women in this study received approximately 3.5 times the conventional estrogen dosage used to treat postmenopausal women. Medroxyprogesterone did not appear to enhance bone mineral in women with either amenorrhea or oligomenorrhea.

The authors conclude that treatment with oral contraceptives was associated with an improvement in lumbar spine, total bone mineral content and bone mineral density in young women with hypothalamic amenorrhea. There was no evidence that oral medroxyprogesterone therapy produced the same beneficial results.