Effects of an oral contraceptive (norgestimate/ethinyl estradiol) on bone mineral density in women with hypothalamic amenorrhea and osteopenia: an open-label extension of a double-blind, placebo-controlled study

Contraception. 2005 Sep;72(3):206-11. doi: 10.1016/j.contraception.2005.03.007.


Objective: The effects of long-term triphasic oral contraceptive administration on bone mineral density (BMD) were investigated in premenopausal women with hypothalamic amenorrhea (HA) and osteopenia.

Methods: After completing three 28-day cycles in the double-blind phase of a placebo-controlled trial, women (mean age, 26.7 years) who received norgestimate 180-250 microg/ethinyl estradiol 35 microg (NGM/EE, n = 15) or placebo (n = 12) in the double-blind phase were to receive open-label NGM/EE for 10 additional cycles.

Results: For subjects completing > or =10 NGM/EE treatment cycles, mean posteroanterior total lumbar spine BMD (L1-L4) increased from 0.881+/-0.0624 g/cm2 at baseline (last visit prior to NGM/EE) to 0.894+/-0.0654 g/cm2 at final visit (p = .043); no significant changes in hip BMD occurred. Decreases in N-telopeptide, osteocalcin, procollagen type I propeptide and bone-specific alkaline phosphatase levels indicated effects on bone metabolism.

Conclusions: Long-term administration of triphasic NGM/EE to osteopenic women with HA may increase total lumbar spine BMD.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Absorptiometry, Photon
  • Adolescent
  • Adult
  • Amenorrhea / complications
  • Biomarkers / metabolism
  • Bone Density / drug effects*
  • Bone Diseases, Metabolic / complications
  • Bone Diseases, Metabolic / metabolism
  • Contraceptives, Oral, Synthetic / administration & dosage
  • Contraceptives, Oral, Synthetic / pharmacology*
  • Double-Blind Method
  • Ethinyl Estradiol / administration & dosage
  • Ethinyl Estradiol / pharmacology*
  • Female
  • Humans
  • Hypothalamic Diseases / complications
  • Lumbar Vertebrae / diagnostic imaging
  • Norgestrel / administration & dosage
  • Norgestrel / analogs & derivatives*
  • Norgestrel / pharmacology


  • Biomarkers
  • Contraceptives, Oral, Synthetic
  • Norgestrel
  • Ethinyl Estradiol
  • norgestimate