Medical Cannabis for Polycystic Ovary Syndrome (PCOS)

Summary

Endocannabinoid system (ECS) dysfunction, decreased expression of fatty acid amide hydrolase (FAAH), and overexpression of CB1 receptors can be found in the adipose tissue of women with Polycystic Ovary Syndrome (PCOS). It is possible that medical cannabis can be used to re-regulate the ECS in those with PCOS, but there is no definitive evidence of this. It is possible that cannabinoids like CBD can be used to manage some of the side effects and comorbidities of PCOS, including pelvic pain, anxiety, and sleep disorders. However, we must consider the negative impact cannabis, and THC in particular, can have on fertility, which is dramatically reduced in those with PCOS.

Medical Cannabis for PCOS: Pros

• One study shows that women with PCOS have a decreased expression of fatty acid amide hydrolase (FAAH), suggesting that ECS dysfunction is involved in PCOS. Medical cannabis could therefore be used to re-regulate the ECS if dosed appropriately.
• Plant-derived cannabinoids (phytocannabinoids) like tetrahydrocannabinol (THC) and cannabidiol (CBD) can be used to manage pelvic pain, anxiety, and sleep disorders like insomnia and sleep apnea in women with PCOS.
• PCOS is associated with an increased risk of metabolic disorders (obesity/overweight, diabetes, and hypertension), and medical cannabis may be used to help manage them.

Medical Cannabis for PCOS: Cons

• Some studies suggest that cannabis can negatively impact fertility.
• Overexposure to cannabinoids affects several aspects of female fertility and reproduction: “In females, chronic exposure to cannabinoids has been shown to delay sexual maturation, cause menstrual cycle disruption, depress ovarian follicular maturation, and reduce serum concentrations of LH and sex hormones.”
• There are few, if any, studies or clinical trials on medical cannabis for PCOS, and this makes it difficult to determine the efficacy of medical cannabis for PCOS.

Data Overview

• Total Studies = 1 (under “Ovarian Dysfunction”)
• Positive Studies = 1
• Inconclusive Studies = 0
• Negative Studies = 0
• 1 Lab Study (positive)
• One study shows that women with PCOS have a decreased fatty acid amide hydrolase (FAAH) expression.
• Possible Overall Efficacy: Low to Moderate, as there are few studies in this area.

Introduction: What is Polycystic Ovary Syndrome (PCOS)?

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. PCOS is related to a dysfunction of the hypothalamic-pituitary-ovarian (HPO) and is defined by three features:

1. Polycystic ovaries, where your ovaries enlarge and contain many fluid-filled sacs (follicles) surrounding the eggs.
2. Excess levels of the “male hormone,” androgen. This can cause physical signs like excess facial or body hair.
3. Irregular periods as well as excessively heavy periods.

Pelvic pain, acne, patches of thick skin, and difficulty getting pregnant are symptoms of PCOS. PCOS affects between 4% and 20% of women of reproductive age worldwide, although some estimates suggest that it can affect one in every four women (26%) of reproductive age worldwide.

Both genetic and environmental factors can cause PCOS. Risk factors include obesity, lack of physical activity, and a family history of PCOS.  PCOS also increases the risk of stroke, cardiovascular diseases (CVDs), type-2 diabetes, anxiety, depression, sleep apnea, autoimmune thyroiditis, and many other conditions. PCOS does not significantly reduce life expectancy on its own, but many comorbidities can.

Several methods for treating PCOS include exercise, an improved diet, and maintaining a healthy weight. Medicines for symptoms like anxiety, depression, reduced fertility, hair growth, and irregular periods may also be prescribed. Examples include clomifene (an anti-estrogen medication used to treat infertility in women who do not ovulate), antidepressants, metformin (for diabetes), statins (to control cholesterol), and NSAIDs like ibuprofen to control pain and inflammation.

The Endocannabinoid System (ECS) and The Reproductive System

The endocannabinoid system (ECS) is involved in several reproductive functions in females, including the release of gonadotropin hormone, regulation of oocyte and follicle maturation, embryo transport through the oviduct, and fertility and implantation of the blastocyst (a rapidly dividing ball of cells 5-6 days after fertilization).

The ECS is closely associated with the hypothalamic-pituitary-ovarian (HPO) axis, and dysregulation of the ECS can lead to dysfunction of the HPO axis. Both cannabinoid receptors, CB1 and CB2, have been found in the ovary, and CB1 receptors have been identified in the hypothalamus and anterior pituitary. Anandamide (AEA) and FAAH are expressed in several tissue types of the ECS, including the ovaries, oviducts, endometrium, and myometrium.

Can Medical Cannabis Help Manage PCOS?

There are few studies on the use of medical cannabis for managing PCOS, and there is no definitive evidence that medical cannabis or CBD can help treat PCOS directly. Still, there is evidence that they can be used to help manage some of the side effects and comorbidities of PCOS, including diabetes, stress, pain, inflammation; sleep disorders; and anxiety.

HPO axis disruption may also be re-regulated by careful dosing phytocannabinoids, as endocannabinoid disruption is associated with PCOS. Women with PCOS also have an overexpression of CB1 receptors in adipose tissue, which is associated with insulin resistance. Targeting cannabinoid receptors with phytocannabinoids like THC, CBD, tetrahydrocannabivarin (THCV), and cannabigerol (CBG) may help inhibit glutamate release, which may in turn help reduce cannabinoid receptor expression.

However, there are some potential negatives as well. Disruption of endocannabinoid-dependent regulation of oogenesis (the process of formation of female gametes) by THC or other cannabinoids may make conception difficult, and THC may decrease fertility. However, there is no similar evidence for CBD, with some even suggesting that CBD may improve fertility. CBD may also help manage several symptoms of PCOS (e.g., inflammation and mood disorders) with far fewer side effects than many other prescription medications.

Overall

Sadly, there is little research into PCOS, let alone how well medical cannabis works to manage its signs and symptoms. Some research suggests that ECS dysregulation is involved in developing PCOS, as the ECS is so intimately tied to the HPO axis. This means that careful application of phytocannabinoids may help re-regulate the ECS and HPO axis.

However, phytocannabinoids, THC in particular, can also potentially cause HPO axis dysregulation in healthy females, reducing fertility and affecting the menstrual cycle. Although most studies are on rodents, these findings can be seen in humans to some extent. However, a definitive causal relationship has not been established between cannabis use and reduced fertility.

As PCOS is a very understudied health problem, despite its prevalence, learning more about the condition and how the ECS is involved in the reproductive system would go a long way to improving the quality of life of millions of women worldwide.