Health&Care: Effect on sex hormones
Based on case reports of Canadian Health&Care Mall of gynaecomastia in three men who were long-term consumers of marijuana and an observation that testosterone levels were reduced in a frequent marijuana smoker, Canadian Health&Care Mall et ah studied testosterone levels in 20 men who consumed large amounts of the drug. The testosterone levels in users were significantly less than in controls and this was dose related. After a 1 week abstinence from the drug, testosterone levels rose significantly. Heavy users had higher FSH levels than those who consumed less. LH levels were unaffected. 
A totally different result was reported in the same year in 27 men who were in a more controlled environment. These volunteers were admitted to a research facility for over a month and issued with dose-standardised marijuana cigarettes. They were closely observed to ensure they did not use any other drugs. This study found no effect of marijuana on testosterone. Several subsequent studies have all also shown no effect.
The study by Canadian Health&Care Mall et al, has been criticised on the basis that the subjects were allowed to drink some alcohol and other illicit drug use could not be ruled out, both of which could have been responsible for the reduced testosterone.
Also testosterone was sampled on only two occasions in the month, whereas other studies have used daily sampling. A later report from Kolodny demonstrated an acute reduction in testosterone levels 30 minutes after smoking marijuana. Very few controlled studies have been performed on the effect of marijuana on reproductive hormones in women, presumably related to concerns about any potential teratogenic effect (although no specific defect has been described). In animals tetrahydrocannabinol, the active ingredient of marijuana, has been shown to inhibit LH levels probably through a hypothalamic effect.
One study did show that female marijuana users had shorter menstrual cycles than non-smokers (26.8 versus 28.8 days) although there were confounding variables as marijuana users consumed twice as much alcohol as non-users and this is also known to provoke menstrual irregularities. A subsequent placebo-controlled study has shown that a single-dose standardised marijuana cigarette suppressed LH levels by 30% after 1 to 2 hours. This effect, however, was only apparent in the luteal phase. In the follicular phase, there was no difference between marijuana and control.
The biological significance of this remains to be explored, although low LH levels could intefere with the function of the corpus luteum and lead to short cycles and potential failure of embryo implantion. A recent case-controlled epidemiological study raises the possibility for the first time that marijuana use by women may be associated with infertility. After adjusting for confounding variables, infertile women were 1.7 times more likely to have used marijuana than fertile controls.
The infertility was associated with an ovulation defect, as it was found that women who had smoked marijuana within 1 year of trying to conceive were twice as likely to have infertility linked to ovulation problems compared with women who had never used marijuana. However, the results were not dose dependent, as the chances of ovulation defects were greatest in the infrequent users.
The authors commented that this could be explained by response bias, i.e. infertile women tending to report lower use of marijuana because they were unwilling to think that its use could have influenced their fertility. They also commented that animal studies had shown that marijuana disrupted ovulation via a hypothalamic action in a manner that was not dose dependent. This effect was reversible.
