The Effects of Synthetic 19-Norprogestins on Osteoblastic Cell Function Are Mediated by Their Non-Phenolic Reduced Metabolites

The study investigated the effects of synthetic 19-norprogestins, specifically norethisterone (NET) and levonorgestrel (LNG), on osteoblastic cell function in neonatal rat osteoblasts. While progesterone showed no significant impact, NET and LNG, along with their A-ring reduced derivatives, significantly promoted osteoblast proliferation and differentiation, mimicking estradiol's effects. The study found that these effects were mediated by the non-phenolic metabolites of the progestins, as evidenced by the inhibition of osteoblast differentiation and mineral deposition by finasteride, a 5α-reductase inhibitor, and the suppression of proliferation by a steroidal antiestrogen. These findings suggested that the A-ring reduced derivatives of NET and LNG have intrinsic estrogen-like effects, providing insights into the mechanism of 19-norprogestins in bone restoration for postmenopausal women and implications for hormone replacement therapy.