Marijuana and its link to Gynecomastia

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Endocrine Effects of Marijuana

In the 35 years since the active compound of marijuana, 9-tetrahydrocannabinol, was isolated, the psychological and physiological impact of marijuana use has been actively investigated. Animal models have demonstrated that cannabinoid administration acutely alters multiple hormonal systems, including the suppression of the gonadal ste-roids, growth hormone, prolactin, and thyroid hormone and the activation of the hypothalamic-pituitary-adrenal axis. These effects are mediated by binding to the endogenous cannabinoid receptor in or near the hypothalamus. Despite these findings in animals, the effects in humans have been in- consistent, and discrepancies are likely due in part to the de- velopment of tolerance. The long-term consequences of mari- juana use in humans on endocrine systems remain unclear.
Journal of Clinical Pharmacology, 2002


EFFECTS ON REPRODUCTIVE HORMONES IN MALES
Studies in male rodents have shown significant de-creases in both testosterone and gonadotropins with acute administration of THC due to inhibition of the GnRH pulse generator in the hypothalamus. Similar effects have been demonstrated in primates. In the rhe-sus monkey, THC reduced testosterone levels by 65%, which lasted 1 hour. Chronic effects of cannabinoid ad-ministration are less clear. Although dose-dependent decreases in LH have been observed with chronic ad-ministration of THC, the effect of chronic exposure is less dramatic than that of acute administration and may be related to the development of tolerance.
Human studies investigating the effects of cannabinoids on reproductive hormones have been conflicting. Lower testosterone levels have been re-ported in chronic marijuana users compared to nonus-ers, and acute decreases in both LH and testosterone have been observed after marijuana smoking, but multiple subsequent studies have not confirmed these findings. In one study, heavy chronic users were found to have similar testosterone levels compared to casual users at baseline and did not experience any sig-nificant alterations in testosterone after a 21-day period of intense marijuana smoking in a controlled research setting. A subsequent study of similar design by the same investigators showed no significant changes in integrated LH levels over the study period.These in-consistent observations may be due to differences in study design but also may reflect the development of tolerance, as suggested by the animal studies. Down-regulation and desensitization of CB1 receptors in the hypothalamus may underlie the weakening of ef-fect observed with chronic cannabinoid administra-tion.


GYNECOMASTIA
Gynecomastia is defined as the accumulation of breast tissue in men and results from increases in the circulat-ing estrogen/androgen ratio.Marijuana has been associated with the development of gynecomastia in an early case series, but a case control study showed no association. Given the effects of marijuana on the HPG axis in males and the possibility that noncannabinoid components of marijuana smoke have affinity to the estrogen receptor, an association with gynecomastia is plausible but has not been convincingly demonstrated.