The Role of Endocannabinoid System in Menopause and Its Related-Diseases

Review Article

Austin J Obstet Gynecol. 2021; 8(4): 1177.

The Role of Endocannabinoid System in Menopause and Its Related-Diseases

Torella M1#, Tortora C1#, Argenziano M1, Di Paola A2, Riemma G1, Di Leva C1, La Verde M1 and Rossi F1*

1Department of Woman, Child and General and Specialist Surgery, University of Campania “Luigi Vanvitelli”, Italy

2Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, Italy

#Contributed Equally to this Work

*Corresponding author: Rossi F, Department of Woman, Child and General and Special Surgery, University of Campania “Luigi Vanvitelli” Via De Crecchio, 4 - 80138 Naples, Italy

Received: March 13, 2021; Accepted: March 25, 2021; Published: April 01, 2021


Menopause is a crucial event in women’s health, characterized by the cessation of ovarian function. The estrogens deficiency exposes women to several diseases, including obesity, osteoporosis, cardiovascular diseases and cancer. Menopause-related diseases deeply impact on women’s quality of life and represent a serious public and economic health burden. The Endocannabinoid System (ECS) includes Cannabinoid Type 1 (CB1) and Cannabinoid Type 2 (CB2) receptors, endocannabinoids and all the enzymes involved in their biosynthesis and degradation. It plays a significant role in energy balance, bone metabolism, muscular contractility, vascular tone and cancer progression. CB1 activation is responsible for increasing food intake and body weight, stimulating osteoclast activity, inhibiting oxidative stress and preventing cancer progression. Conversely, the stimulation of CB2 induces a reduction in food intake and in body weight, inhibits osteoclast activity, prevents vascular risk and reduces cancer cells proliferation. Moreover, several polymorphic variants of cannabinoid receptors genes are involved into obesity and osteoporosis.

In menopause, the alteration of cannabinoid receptors expression and endocannabinoids levels as well as their role in hormone-related pathways could act a leading role in different pathologies (obesity, osteoporosis, cardiovascular diseases and cancer). Therefore, ECS could be considered a possible prognostic marker and a therapeutic target to oppose the harmful effects of these menopause-related diseases. In this review we aimed to summarize the current state-of-knowledge concerning the impact of ECS on major health issues of postmenopausal women.

Keywords: Menopause; Endocannabinoid system; Obesity; Osteoporosis; Cardiovascular disease; Cancer


Menopause is a crucial event of women life. The process is sustained by a significant decrease of estrogens and progesterone production by ovarian tissues due to natural depletion and aging of the oocytes [1]. Natural menopause is diagnosed after 12 months amenorrhea not related to pathologies, surgery or any kind of therapy (chemo- or radiotherapy) and in the majority of cases it occurs after the age of 51 [2,3]. Conversely, surgical menopause occurs when the cessation of ovarian function is related to surgical removal or medical conditions. Among the clinical conditions associated to early-onset menopause, premature ovarian failure is the leading cause and happens when the cessation of ovarian function happens before the age of 40. It could be idiopathic or related to several pathologies (i.e. autoimmune disorder, diabetes mellitus, and thyroid diseases [4].

Postmenopausal women could experience several symptoms, sometimes responsible for strong life quality compromise. Although changing in intensity and frequency from a patient to patient, those symptoms include Vasomotor Symptoms (VMS), sleep disturbances, genitourinary syndrome of menopause (i.e., vulvovaginal atrophy), as well as psychologic and emotional disorders [4,5]. Moreover, the earlier is the onset of menopause the most elevated is the risk of cardiovascular diseases. Other complications especially related to reduction in estrogen levels are inflammation, immunological dysfunction, anemia, alteration in bone metabolism, cognitive disorders, alteration in RAS proteins pathway, frequently altered in cancer [6].

The Endocannabinoid System (ECS) is a complex endogenous signaling system constituted by: - two 7-transmembrane-domain and G protein-coupled receptors, the Cannabinoid Receptor Type-1 (CB1) and the Cannabinoid Receptor Type-2 (CB2); their ligands (or endocannabinoids), N-arachidonoylethanolamine or anandamide (AEA) and 2-arachidonoylglycerol (2-AG); the enzymes responsible for endocannabinoid biosynthesis, named N-Acyl Phosphatidylethanolamine-Specific Phospholipase D (NAPE-PLD) and Diacylglycerol Lipase (DAGL), and, for their inactivation, Fatty Acid Amide Hydrolase (FAAH) and Monoacylglycerol Lipase (MAGL) [7]. ECS is involved in several biological functions: appetite regulation, pain management, organism development, modulation of inflammatory processes and immune response [8]. Considering the variety of physiological functions in which it is involved and also the evidences about its dysregulation in the pathogenesis of many diseases, ECS has been often proposed as therapeutic target for several conditions, including metabolic disorders [9], osteoporosis [10], cardiovascular disease [11] and cancer [12]. Moreover, a crosstalk between ECS and sex hormones is well-documented, in particular the alteration of estrogens and progesterone production in postmenopausal women is strongly related to alteration in ECS activity (Figure 1) [13].

Citation: Torella M, Tortora C, Argenziano M, Di Paola A, Riemma G, Di Leva C, te al. The Role of Endocannabinoid System in Menopause and Its Related-Diseases. Austin J Obstet Gynecol. 2021; 8(4): 1177.