Dr. Weeks’ Comment: Progesterone is a human hormone ( made by both women and men) and many doctors recommend it because it build bone (stimulate osteoblasts) and is helpful for people with osteoporosis or bones which are failing to knit after fracture. Oral progesterone (is less effective than transdermal progesterone and under all circumstances AVOID the toxic progestins which are typically referred to as a “progesterone” but which are really a near-miss, knock-off of the natural hormone – they are dangerous.
Progesterone and Bone: Actions Promoting Bone Health in Women
Received 16 February 2010; Revised 31 July 2010; Accepted 26 August 2010
Academic Editor: E. M. Lewiecki
Estradiol () and progesterone () collaborate within bone remodelling on resorption () and formation (). We integrate evidence that may prevent and, with antiresorptives, treat women’s osteoporosis. stimulates osteoblast differentiation in vitro. Menarche () and onset of ovulation () both contribute to peak BMD. Meta-analysis of 5 studies confirms that regularly cycling premenopausal women lose bone mineral density (BMD) related to subclinical ovulatory disturbances (SODs). Cyclic progestin prevents bone loss in healthy premenopausal women with amenorrhea or SOD. BMD loss is more rapid in perimenopause than postmenopause—decreased bone formation due to deficiency contributes. In 4 placebo-controlled RCTs, BMD loss is not prevented by in postmenopausal women with increased bone turnover. However, 5 studies of -MPA co-therapy show greater BMD increases versus alone. fracture data are lacking. prevents bone loss in pre- and possibly perimenopausal women; progesterone co-therapy with antiresorptives may increase bone formation and BMD.
Osteoporosis has been considered primarily because of estrogen deficiency at menopause since Fuller Albright . Most scientists view estradiol as women’s sole bone-active gonadal steroid. In reality, estradiol and progesterone work together in every tissue in women’s normal physiology . Estrogen plays positive roles in bone biology and osteoporosis prevention and treatment primarily through decreasing bone resorption [3–5]. There is also compelling evidence that powerful bone-destructive cytokines such as IL-1, IL-6, and TNFα are released and increase rapidly with dropping estradiol levels, as occurs with surgical menopause . Estradiol achieves its positive bone effects largely through two key actions: facilitation of vitamin D-related intestinal calcium absorption [4, 7] and suppression of bone resorption through the osteoprotegerin/RANK/RANKL system . It is also clinically obvious that premenopausal women with amenorrhea have lower estradiol levels and lower bone mineral density (BMD) and/or lose bone rapidly .
Not until recently did randomized, placebo-controlled trial data from the WHI studies show that treatment with conjugated equine estrogen (CEE) plus medroxyprogesterone (MPA) or with CEE alone (in women with hysterectomy) prevented osteoporotic fractures in asymptomatic postmenopausal women ages 50–79 [5, 9]. Estradiol’s role in human bone health is unmistakable. However, progesterone is usually a present, but an unrecognized partner in bone. With amenorrhea and surgical or natural menopause, not only are estradiol levels low or dropping, progesterone levels are also low. While, in these conditions, estrogen and progesterone deficiency are nearly indistinguishable, progesterone deficiency precedes low estradiol levels in perimenopause , for example, and with ovulatory disturbances, occurs silently in regular cycles with normal estrogen levels ……..
Knowledge of progesterone’s actions in the context of the latest genetic, receptor, and bone ligand systems is in its infancy—relationships may well exist between progesterone and the immune system through osteoblast and hematopoietic stem cell interactions in bone marrow , through progesterone’s known brain anti-inflammatory and antiapoptotic actions , and through potential relationships with emerging bone-related molecules such as sclerostin, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF), to name a few. These molecular biology issues, however, are beyond the scope of this primarily clinical and therapeutic review.
Over the last 20 years , a number of controlled trials and prospective studies suggest that progesterone may have a role in treatment of pre- or perimenopausal women with regular, estrogen-sufficient menstrual cycles who, however, are also experiencing ovulatory disturbances (anovulation, or short luteal phase length cycles). The most prevalent of abnormal cycles are subclinical ovulatory disturbances (SOD) that are unremarkable because they occur within regular, asymptomatic menstrual cycles [11, 18]. They have an increased incidence in normal weight women with subclinical cognitive dietary restraint , women working shifts and in stressful environments. However, currently there are no published data about effects of progesterone on human bone architecture and bone quantitative histomorphometry in either the cortical or cancellous bone compartments, or about the potential of molecularly identical progesterone to decrease fracture risk.
Although the dominant osteoporosis paradigm for women is, and should remain, centred on estrogen, progesterone is emerging as an important partner hormone that collaborates with estrogen. In vitro studies of human osteoblasts in culture, prospective studies in adolescent, premenopausal, perimenopausal, and postmenopausal women all indicate that progesterone—likely working through bone formation pathways—plays an active role in maintaining women’s bone and in osteoporosis prevention.
Finally, although progesterone or MPA therapy does not prevent bone loss when bone turnover is high, evidence from a number of randomized controlled trials suggests that progesterone as co-therapy with an antiresorptive agent may have promise. Data on progesterone co-treatment and fracture prevention are urgently needed, as is more information about the microarchitectural and histomorphometric changes during progesterone therapy.
Progesterone, a physiological ovarian steroid that is normally secreted in high levels for two weeks per menstrual cycle in ovulatory menstruating women, appears to have complementary bone actions with estrogen and antiresorptive therapies. Progesterone deserves to be studied more as a new and emerging agent for achieving and preserving peak bone mass, for prevention of pre- and perimenopausal bone loss, and, with an antiresorptive therapy, in increasing BMD and potentially decreasing fractures in postmenopausal women.