Can Cannabis Replace Risky Hormone Replacement Therapies (HRT) for Menopause? - RxLeaf

Can Cannabis Replace Risky Hormone Replacement Therapies (HRT) for Menopause?

Dragana Komnenov PhD
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Menopause involves dysregulation in the endocannabinoid system, so it makes sense that cannabis may be able to replace higher risk therapies, like HRT.

Life expectancy of women has almost tripled over the last two centuries, rising from 25 years to 70 years of age. Aging in women is associated with the gradual loss of the female reproductive hormones, estrogen and progesterone. These diminish until the point that menopause is reached;  men do not experience the same hormonal decline requiring HRT.

There are additional health care challenges this hormonal change brings, including increased risk of certain types of cancer. On the other side of this, treatment for cancers in women has been shown to accelerate entry into menopause.

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There appears to be a crucial interconnectedness of hormones and disease risk, and the loss of hormones in menopause is potentially impactful on all aspects of female health and quality of life. So far, the mainstay treatment options have included hormone replacement therapy (HRT, with both estrogen and progesterone) or estrogen replacement therapy (ERT).

Estrogen is a steroid hormone and as such, is involved in regulation of many cellular processes. It is essential in bone health and female sexual health. Therefore, it is expected that the loss of estrogens will be detrimental on these important aspects of physiology. Therefore, replenishment of the lost estrogen in menopause is expected to mitigate these detrimental effects. Although replacement of estrogen and progesterone has proven to be highly effective in alleviating menopausal symptoms, including hot flashes, night sweats, sexual disorders, and insomnia and in preventing bone loss (osteoporosis), it doesn’t come without a price. Indeed, an expensive one, some might say.

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Preclinical data has highlighted that estrogen and progesterone are likely involved in the induction and progression of breast, endometrial, and epithelial ovarian cancers. This coupled to an already increased risk of cancer with aging does not bode well in the eyes of women seeking relief of menopause with HRT or ERT. What are the alternatives?

It has been suggested that the endocannabinoid system (ECS) balance is perturbed in menopause, suggesting that estrogen and progesterone interact with the ECS somehow and keep each other in balance. One of the estrogens, called 17b-estradiol, or E2 for short, has been suggested to be involved in the regulation of the ECS, albeit the evidence still lacks robustness. E2 has the potential to both stimulate and inhibit the release of anandamide (AEA), depending on the tissue in question.

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One group of researchers investigated the changes in plasma AEA during menstrual cycle of healthy women and found a positive correlation between E2 and AEA, suggesting that E2, in fact, regulates AEA . Therefore, one can expect that in menopause, AEA decreases as well, leading to ECS imbalance.

The question then arises, can the reversal of depletion of endocannabinoids with exogenous cannabinoids bring the system into balance? Indeed, this may be just the explanation provided by several promising studies showing beneficial effects of cannabinoids on comorbidities that occur with menopause. It has been shown that cannabinoids provide protection from osteoporosis in menopause.

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CB2 receptor is expressed in cells of the bone and its activation stimulates bone formation and inhibits bone resorption. Mice lacking the gene for CB2 show low bone mass, suggesting that physiologic involvement of CB2 is associated with maintaining bone remodeling at balance. Likewise, in humans, slight changes in the gene (called polymorphisms) encoding CB2, CNR2, are strongly associated with postmenopausal osteoporosis. Most importantly, preclinical studies have shown that a synthetic CB2-specific agonist reverses bone loss. It is tempting to speculate that THC and CBD may have the same effect via their interactions with CB2 receptor, acting as cannabinoid drugs to combat osteoporosis.

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Additionally, experimental evidence has shown that cannabinoids can protect from breast cancer. In the context of menopause, this is extremely important, since not only would cannabinoids reduce the risk of breast cancer associated with aging, but they would also mitigate the risk associated with HRT and ERT. Cannabinoids have been shown to kill cancer cells, prevent their growth and migration throughout the body. Specifically, THC has been shown to arrests breast cancer cell proliferation, by preventing activation of the estrogen receptor via its ligand E2.

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Currently, there are no studies directly investigating cannabis use in relieving menopausal symptoms. Nevertheless, some important studies have been published highlighting the benefits of cannabinoids in comorbidities that occur during menopause, such as bone loss and risk of cancers (particularly breast cancer). The approach to therapy would therefore have to be individualized, as each woman experiences different symptoms during menopause. There seems to be a relief on the horizon for women who are reluctant about taking HRT and ERT, and especially whom are cancer survivors.


Dragana Komnenov
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