Progesterone is a term that is incorrectly used interchangeably to describe both progesterone which is “chemically identical” to what the body naturally produces and synthetic derivatives. Synthetic progestins are analogues of progesterone and have been developed because they are patentable, more potent, and have a longer duration. Medroxyprogesterone acetate, the most commonly used synthetic progestin, was shown in a large study to cause significant lowering of HDL “good” cholesterol, thereby decreasing the cardioprotective benefit of estrogen therapy. Side effects are a frequent cause for discontinuation of HRT. Only about 20% of women who start synthetic HRT remain on it two years later.

Progesterone:

• is commonly prescribed for perimenopausal women to counteract “estrogen dominance” which occurs when a woman produces smaller amounts of progesterone than normal relative to estrogen levels.
• alone, or combined with estrogen, may improve Bone Mineral Density.
• minimizes the risk of endometrial cancer in women who are receiving estrogen.
• is preferred by women who had previously taken synthetic progestins.

The benefits of progesterone are not limited to the prevention of endometrial cancer in women who are receiving estrogen replacement. Progesterone therapy is not only needed by women who have an “intact uterus”, but is also valuable for women who have had a hysterectomy. Vasomotor flushing is the most bothersome complaint of menopause and is the most common reason women seek HRT and remain compliant. For over 40 years, estrogens have been the mainstay of treatment of hot flashes, but progesterone may be effective as well.

Progesterone for Brain and Bone Health

Progesterone (P4), a well-known neurosteroid, is produced by ovaries and placenta in females and by adrenal glands in both sexes. Progesterone also has multiple non-reproductive functions and is synthesized by central nervous system (CNS) tissues to perform various vital neurological functions in the brain.

Experimental, epidemiological, and clinical data indicate that progesterone is active in bone metabolism. Progesterone appears to act directly on bone by engaging an osteoblast receptor or indirectly through competition for a glucocorticoid osteoblast receptor. Progesterone seems to promote bone formation and/or increase bone turnover. It is possible, through estrogen-stimulated increased progesterone binding to the osteoblast receptor, that progesterone plays a role in the coupling of bone resorption with bone formation.

In the central nervous system, progesterone helps to regulate cognition, mood, inflammation, mitochondrial function, neurogenesis and regeneration, myelination and recovery from traumatic brain injury. A substantial body of experimental evidence from animal models documents the neuroprotective role of progesterone in various CNS injury models, including ischemic stroke. Extensive data have revealed that progesterone elicits neuroprotection through multiple mechanisms and systems in an integrated manner to prevent neuronal and glial damage, thus reducing mortality and morbidity. Progesterone has been described as safe for use at the clinical level through different routes in several studies.

Progesterone alone or in combination with estradiol therapy may improve the quality of life for a postmenopausal woman, whether or not she has an intact uterus. In addition to mitigating or preventing vasomotor symptoms or postmenopausal bone loss, oral progesterone causes drowsiness and can be administered at bedtime as part of an HRT regimen, and in this way can help with sleep.

Journal of Osteoporosis Volume 2010, Article ID 845180.

Progesterone and Bone: Actions Promoting Bone Health in Women

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Endocr Rev. 1990 May; 11(2):386-98.

Progesterone as a bone-trophic hormone

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Front Neuroendocrinol. 2008 May; 29(2):313-39.

Progesterone receptors: form and function in the brain

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J Environ Pathol Toxicol Oncol. 2017; 36(3):191-205.

Neurosteroids and Ischemic Stroke: Progesterone a Promising Agent in Reducing the Brain Injury in Ischemic Stroke

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