Influence of progestagens on bone health. Bone changes related to ovulatory disturbances and low progesterone levels

Purpose: To enhance trans-disciplinary understanding of bone changes in women, between the boundaries internal medicine, experimental orthopedics/surgery and gynecology. Major sources of information: A two-decade literature archive on factors affecting female bone metabolism, supplemented by a search of the recent experimental publications, and including work from our own working group on bone and females hormones. Data synthesis in the model context: In experiments in human osteoblast cultures from female femur bone, which were sufficiently estrogenized to induce progesterone receptors (PGR), progesterone showed remarkable dose-response curves explaining many clinical observations. In bone research negating progesterone effects, the fact that PGR induction needs a minimum of 4–7 days of estrogen exposure and may need a female genetic endowment is often neglected. There is insufficient information on female animals in many bone models. Incorporation the new understanding into clinical and/or research relevance: While ovulation itself shows parallels with inflammatory processes for a short time, lack of progesterone or its receptor may prolong this state of inflammation. Progestin resistance is a feature of endometriosis, and 19% of women with early stage endometriosis are anovulatory. Bone marrow derived tem cells are known to play a role in endometriosis, but bone loss has only been evaluated regarding estrogen deprivation treatment in this diesease. Based on clinical observations of premenopausal women presenting with both endometriosis and osteoporosis without prolonged estrogen-suppressive treatment, a joint mechanism involving inflammatory mechanisms may play a role. Conclusion: Chronic inflammatory processes may be maintained by anovulation and lack of progesterone and may preferentially affect women with PCOS (for whom this has already been investigated) and also with endometriosis. This may also partly explain the preponderance of women in osteoporotic disease.