Women's Health Spotlight: Hormone Replacement Therapy and the Endocannabinoid System

The use of compounded bioidentical hormone replacement was originally developed in 1939 for women who had undergone radical hysterectomies. The longest-studied type of hormone replacement therapy (or HRT as it is commonly known), it was primarily utilized in Europe and Australia until about 2011, when innovators in the field of integrative and functional medicine started reintroducing the therapy into the United States. A reintroduction made necessary by HRT’s controversial path to acceptance.

n the United States, hormone replacement therapy began in the 1960s and later gained traction in the 1990s with The Women’s Health Initiative, a long-term national health study funded by the National Heart, Lung, and Blood Institute. It was one of the first clinical trials on chronic postmenopausal conditions. In 2002, the first results were released, and the study was prematurely halted, when the initial results indicated HRT may have more detrimental effects than benefits.


This widespread publicity created panic and new guidance to doctors prescribing HRT. Since that time, review of the WHI trial analyses and new studies demonstrated that the use of HRT in younger women or in early postmenopausal women had a beneficial effect on the cardiovascular system, reducing coronary disease and all-cause mortality. Further studies on the use of compounded Bio-Identical Hormone Replacement Therapy (BHRT) subcutaneous pellet therapy have indicated that it may benefit the recipients in bone, brain, and breast health.


In a new study from The Journal of Clinical Investigation, researchers point to evidence that there is a “critical window” for women where hormone replacement can reduce the depression- and memory-loss-related symptoms associated with menopause. Researchers examined hormone levels, biochemical regulators of CB1, and mice’s ability to adaptively learn after ovariectomized mice were induced into menopause. Through their research, Zhang, et al. discovered that activating CB1 receptors may prolong this window.


In the study, estrogen administration was beneficial for the mice, improving learning and reducing memory loss, but only if administered immediately after deprivation via ovariectomy. These beneficial effects were not seen when treatment was given three months after the onset of the menopause model, suggesting the so-called “time window of opportunity” in hormone therapy. Upon cotreatment with CB1 receptor agonists, however, the hormone treatment became more effective, and the window of opportunity was prolonged.


While the experimental methods cannot be directly translated to humans, the interplay between sex hormones and the endocannabinoid system is increasingly recognized as relevant to health and medicine. Anecdotally, our providers are seeing better results from their patients that combine BHRT therapy with a full spectrum hemp extract, particularly cannabigerol (CBG).


Dr. Michael Jelinek, MD, notes, “My patients report back that they are feeling better when they start CBG before hormone replacement. Those that are being treated with BHRT, and are also using Formula30A, are reporting better outcomes to their hormone optimization when it comes to anxiety, sleep, and energy. If you give women that are on hormones CBG, they do better.” Additional research must be conducted before conclusions of any statistical significance may be drawn, but what we already know about CBG may shed some light on this mechanism.