Progesterone and bone health

Clinical evidence suggests that endogenous progesterone plays a role in postmenopausal bone health. For instance, three in vitro studies revealed progesterone’s effect at increasing osteoblast levels and its ability to promote osteoblast maturation and differentiation. Studies also suggest that progesterone may have a beneficial role in postmenopausal osteoporosis when administered in combination with an antiresorptive agent such as estradiol or conjugated equine estrogen (CEE).

Additionally, there is evidence that combination estradiol and progesterone therapy has a greater effect on bone density compared to estradiol alone, even in women who have undergone a hysterectomy. Therefore, healthcare professionals treating hysterectomized women, who are at high risk for osteoporosis, might consider combining progesterone with their prescribed regimen if the patients are only on estradiol treatments.

Progesterone and hot flashes

Estradiol therapy alone is a well-known treatment for hot flashes in postmenopausal women, but progesterone is also administered in combination with estradiol in treating and preventing symptoms of hot flashes. However, progesterone therapy alone may have unique individual effects at treating hot flashes. One study showed that megestrol (progesterone derivative) 20 mg by mouth twice daily decreased hot flashes by 85% in four weeks. Another study using progesterone cream applied on the skin daily for one year improved or resolved vasomotor symptoms (hot flashes) significantly versus placebo.

Progesterone sedating effects

Progesterone can also have significant effects on sleep, and researchers appear to have a better grasp of its effects on sleep compared to estradiol.When progesterone is administered intravenously, it has direct sedative qualities, stimulating benzodiazepine receptors, which then stimulate the production of the non-rapid eye movement (NREM) related GABA receptors. Progesterone has anxiolytic effects by acting as a GABA agonist, although the exact mechanism remains unclear. Progesterone metabolites, including allopregnanolone and Pregnenolone, act as agonists at the GABAA receptor, resulting in sedative effects.

Progesterone effect on mood & depression

The estradiol-progesterone ratio may also be a key factor in properly treating mood disorders in some female patients. A small study by Dr. Bronson found that a deficiency of progesterone may be a primary factor in mid-life anxiety patterns. This study observed that some patients with high estrogen levels and low progesterone levels “exhibit[ed] extreme rage, followed by conciliatory, self-defeating demeanor.” This behavior pattern may have a pharmacological basis because one of the largest concentrations of progesterone receptors is in the limbic area of the brain, which is the center of emotion possibly related to rage, anger and violence as described by some physiologists. And as previously stated, progesterone has a calming effect as described by its action on GABA receptors in the brain. This suggests that a progesterone deficiency may lead to varying levels of anxiety, depending on the degree of estradiol-progesterone imbalance.

Related to mood disorders and anxiety, premenstrual syndrome (PMS) and postpartum depression both can occur from an abrupt dip in progesterone levels. One study found that both conditions were treated effectively with progesterone in some patients, especially as prophylaxis treatment for PMS and postpartum depression. Combined with Dr. Bronson’s study, this seems to imply that progesterone can be an effective treatment for anxiety in perimenopausal women. Dr. Bronson’s observational study found that treatment was most effective at higher progesterone doses administered topically, with most women treated reporting significant improvements in their emotional health. However, large, randomized, controlled trials are needed to substantiate progesterone’s effectiveness at treating mood disorders and depression.


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