Effect of norethindrone acetate on hormone levels and markers of bone turnover in estrogen-treated postmenopausal women.

There is controversy concerning the effects of progestins on bone. Norethindrone acetate (NETA) is synthetic progesterone that also has estrogenic and androgenic effects. We tested its effects on hormone levels, lipids and biochemical markers of bone turnover in postmenopausal women who were on estrogen replacement therapy. Women were treated with NETA, 5 mg/d for 9 weeks. Estrogenic effects included a marked lowering of follicle stimulating hormone and luteinizing hormone. Androgenic effects included a decrease in sex hormone binding globulin and HDL cholesterol. Bone turnover showed inconsistent responses. Among markers of bone formation, bone specific alkaline phosphatase decreased significantly by 23% while procollagen peptides and osteocalcin showed a non-significant increase. The marker of bone resorption, N-telopeptide crosslinks of collagen, decreased by 19% at 6 weeks. These results indicate that NETA does not have a potent short-term anabolic effect on bone but does have effects that are likely to be mediated through the estrogen and androgen receptors.