Parathyroid hormone for the prevention of bone loss induced by estrogen deficiency

N Engl J Med. 1994 Dec 15;331(24):1618-23. doi: 10.1056/NEJM199412153312404.


Background: Analogues of gonadotropin-releasing hormone (GnRH) are often given to induce hypogonadism in women who have estrogen-dependent disorders such as endometriosis and uterine leiomyomas. Because estrogen deficiency causes bone loss, concern about premature osteoporosis has prevented long-term therapy with GnRH analogues. We conducted a study to determine whether parathyroid hormone could prevent bone loss in women receiving therapy with GnRH analogues.

Methods: We administered human parathyroid hormone (40 micrograms subcutaneously daily) to 20 of 40 women with endometriosis who were being treated with nafarelin (200 micrograms intranasally twice daily) for six months; the remaining 20 women received only nafarelin. Cortical and trabecular bone density and biochemical markers of bone turnover were measured every three months during the six-month study period.

Results: Serum estradiol concentrations fell to postmenopausal values in 36 of the 40 women. In the women who received nafarelin alone, the mean (+/- SE) bone density in the lumbar spine decreased by 2.8 +/- 0.5 percent (P < 0.001) when measured in the anteroposterior projection and by 3.5 +/- 0.8 percent (P < 0.001) when measured in the lateral projection. In contrast, bone density in the lumbar spine did not change when measured in the anteroposterior projection and increased by 3.4 +/- 1.2 percent when measured in the lateral projection (P = 0.01) in the women who also received parathyroid hormone. Bone density at the femoral neck decreased slightly and similarly in both groups. Radial bone density did not change in either group. Serum alkaline phosphatase and osteocalcin concentrations and urinary hydroxyproline and pyridinoline excretion increased (P < 0.001) in the women who received nafarelin plus parathyroid hormone.

Conclusions: Parathyroid hormone can prevent bone loss in the lumbar spine in young women with estrogen deficiency caused by treatment with GnRH analogues.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Bone Density
  • Bone and Bones / metabolism
  • Endometriosis / drug therapy
  • Estrogens / deficiency*
  • Female
  • Humans
  • Injections, Subcutaneous
  • Nafarelin / adverse effects
  • Nafarelin / therapeutic use
  • Osteoporosis / etiology
  • Osteoporosis / metabolism
  • Osteoporosis / prevention & control*
  • Parathyroid Hormone / administration & dosage
  • Parathyroid Hormone / therapeutic use*


  • Estrogens
  • Parathyroid Hormone
  • Nafarelin