Unfortunately, even today, many postmenopausal women who have undergone a hysterectomy have been denied by their doctor access to progesterone, claiming that this hormone is only useful for the uterus. However, an accumulation of data demonstrates that the physiological actions of this hormone extend to several non-reproductive functions. Indeed, a range of organs express progesterone receptors: thyroid, nervous system, blood vessels, breast, bone tissue, muscles and ligaments, bladder, skin, liver, pancreas, intestines, and others, suggesting that it exerts a certain influence. Progesterone is not yet getting the attention it deserves and its contribution to health is vastly underestimated. While it is true that the main producing organs are the ovaries and that the primary role of this hormone is to modulate the uterus for possible pregnancy, this does not mean that progesterone no longer has importance once in menopause, it is quite the contrary!
Hormonal balance, a quest very dear to women’s health, is only made possible through harmonizing (minimally) estrogen and progesterone. Hormonal health involves a partnership and cannot be seen in the absence of one or the other. It is no coincidence that the receptors for both are found in the same tissues. Indeed, progesterone is essential for the activation of estrogen receptors and the latter allows the creation of progesterone receptors. These valuable hormones aid and counterbalance each other in their actions, so both must be present to achieve a balanced hormonal response. This leads us to believe that all bodily tissues need to be exposed to both hormones in order to optimize their performance.
Progesterone and the brain
Progesterone is produced mainly by the ovaries and the placenta during pregnancy, but the brain is also a site of the production of this hormone. In fact, nerve cells are exposed both to progesterone from the reproductive organs (given its lipophilic structure) and also to that which they manufacture themselves. Why so many options? It is because this hormone is essential for the development and maintenance of the functions of this tissue! Animal studies have shown that progesterone can increase the growth of new cells in the brain by activating the expression of genes that promote cell division and inhibit those that suppress it. Progesterone thus participates in the genesis of nerve cells (neurons and glial cells), in the protection of the brain against harm and trauma, in the regeneration of damaged nerve fibers, in myelination (protective layer covering the nerves responsible for the transmission of electrical signals), to the reconfiguration of neural connections involved in learning and memory, in addition to influencing mood(1).
Only progesterone can be converted into allopregnanolone, a metabolite with anxiolytic, anti-depressant, prosocial, sedative, analgesic, and even neuroprotective effects(2-4). It is through its affinity with the GABA-A receptors of the brain that allopregnanolone infuses relaxation, serenity, and a stable mood(5) while promoting restful sleep… everything you need to soothe premenstrual syndrome, a phase of irritability or hormonal insomnia! Moreover, allopregnanolone (under the name Brexanolone) has been approved since 2019 in the United States for the treatment of postpartum depression.(6,7)
Progesterone positively influences neurological health, which is all the more important for the aging brain. There is a natural decrease in cellular turnover with age and since progesterone appears to promote brain cell growth and improves cognitive performance in rodents, this is promising news for the aging human brain. Moreover, progesterone would be able to reverse the cognitive deficits linked to Alzheimer’s disease(8,9) and slow down neurodegenerative conditions such as multiple sclerosis(10). So why deprive yourself of it?
Progesterone and the thyroid
The health of individuals is largely defined by the performance of the thyroid. The latter represents a gland essential to the metabolism of all the organs. Its influence is general, ranging from the activation of genes, the use of oxygen in cells, and bone renewal, not to mention digestive, cardiac, nervous, and reproductive functions, and the list goes on!
Thyroid dysfunctions are not uncommon and progesterone, you guessed it, facilitates the action of this gland. Research shows that progesterone can increase thyroid hormone blood levels in addition to reducing the amount of binding protein for these hormones, which means that more hormones remain available to perform their functions in target tissues(11) of the organism.
Progesterone competes with estrogen. Estrogen is known to interfere with thyroid hormones in the gland itself and around it. This results in a number of symptoms including weight gain and fatigue. When the level of progesterone is low, estrogens, therefore, have free rein in slowing down the metabolism. When enough progesterone is circulating in the body, thyroid hormones speed up cellular performance and utilize stored fat under the influence of estrogen resulting in a boost of energy(12). Among the strategies to normalize the thyroid, the balance between estrogens and progesterone is in order. This is all the more important during pre-menopause when menstrual cycles are often anovulatory, or completely absent during menopause (without the production of progesterone in both cases).
Progesterone deficiency is linked to calcitonin deficiency. Calcitonin is another hormone derived from the thyroid that promotes mineralization in the body by lowering calcium levels in the blood to promote its incorporation into bones and teeth. Calcitonin, assisted by progesterone, thus allows bone remodeling which is extremely precious during menopause due to the gradual progression of osteoporosis.
Progesterone and Bone Health
As we have just seen, progesterone promotes mineral deposition in bones. This is possible, not only via calcitonin but also through its stimulating action on osteoblasts, the cells responsible for renewing bone tissue. Moreover, there is an increase in osteoblastic activity during the luteal phase of the menstrual cycle, the phase following ovulation, when progesterone levels reach their maximum. The role of progesterone seems significant enough that several researchers claim that postmenopausal osteoporosis is, in part, a disease of progesterone deficiency(13).
Progesterone and Heart Health
On this point, the confusion is justifiable! In the literature, there is an amalgam of information concerning synthetic progestins which, although they do not have the same molecular structure as progesterone, pass in the eyes of medicine as equivalents. However, this is a serious mistake because while all progestins by definition have progestogenic activity, they also have a divergent range of other properties which can result in very different clinical side effects when compared to natural progesterone. For example, medroxyprogesterone acetate (synthetic progestin called AMP) increases the risk of stroke, increases the level of C-reactive protein, promotes the proliferation of smooth muscle cells in the arteries, and contributes to the formation of blood clots, are all favorable indicators of cardiovascular disease, while the growing body of evidence shows the exact opposite for natural progesterone(14). This identity theft keeps many doctors from prescribing progesterone to their patients with risk factors for cardiovascular disease because of the bad press attributed to it, despite itself.
A study conducted on several women applying 20mg of progesterone in the form of a cream used daily over a period of 4 weeks, demonstrated no elevation of any of the thrombotic or inflammatory markers studied (protein C, factors V, VII, VIIII, fibrinogen, antithrombin, PAI-1, C-reactive protein, TNFα, IL-6) were observed, compared to previous studies involving synthetic progestins(15,16). Among the factors improved by natural progesterone (transdermal application), we find a regulatory action on blood fluidity and vasodilation, playing a preventive role on venous embolisms, cardiac ischemia, and angina pectoris. Progesterone is, moreover, antispasmodic and diuretic. Through its inhibitory effect on aldosterone, progesterone reduces the absorption of sodium and water. It thus limits the edema that many women experience when menstruation approaches, especially during pre-menopause. Fluid retention is a detrimental factor for cardiovascular health since it can induce hypertension and worsen the risk of heart failure(17). Natural progesterone also improves the profile of blood lipids in favor of HDL cholesterol (known as “good cholesterol”)(18), slowing down, de facto, the development of atherosclerosis.
Since cardiovascular diseases have long been recognized as the leading cause of death in women, the risk of which increases considerably after menopause, and since menopause heralds the appearance of low levels of HDL cholesterol compared to other blood lipids, any safe intervention allowing the strengthening of cardiovascular function should not be ruled out, including hormonal balance!
Véronique Bourbeau, Certified Naturopath
Article initially published in Vitalité Québec, January 2021
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