Effects of alcohol on the male reproductive system

Alcohol Health & Research World, Spring, 1991 by Harlan I. Wright, Judith S. Gavaler, David Van Thiel

Alcohol causes loss of libido, impotence, and sterility in males. Direct damage to testicular cells and impairment of control centers in the brain may help explain the sexual dysfunction.

The association between alcohol abuse and reproductive dysfunction has long been recognized. For example, the Greeks proscribed the use of alcohol on the day of matrimony. Signs and symptoms of inadequate sexual function (hypogonadism) associated with alcohol abuse include testicular atrophy (shrinkage), sterility, impotence, loss of libido, reduction in size of the prostate gland, and decreased sperm production. Hypogonadism may be caused by direct effects of alcohol on the testis; it can also be caused by effects of alcohol on parts of the brain that regulate gonadal function. These parts of the brain include the hypothalamus, located approximately in the center of the brain, and the pituitary gland, located at the base of the brain just below the hypothalamus. The term "hypothalamic-pituitary-gonadal (HPG) axis" refers to the interaction of these three levels of control of testicular function. (The same term refers to the control of ovarian function in the female.) The HPG axis will be described in more detail in a later section.

Research on the mechanisms of alcohol-induced hypogonadism has focused on the HPG axis as well as on the liver as possible targets of alcohol's actions. This article briefly discusses some of this research.

Alcohol, Sexual Function, And The Liver

Because hypogonadism was first reported in alcoholic men with cirrhosis of the liver (Table 1), alcohol-induced sexual dysfunction was initially attributed to liver disease. As reliable methods of quantifying sex hormones became available, levels of the male sex hormone testosterone were measured in the blood of cirrhotic men. Subjects with alcohol-induced liver disease were found to have markedly reduced testosterone levels, while those with advanced liver disease due to other causes often had normal testosterone levels (Chopra et al. 1973; Galvao-Teles et al. 1973; Kent et al. 1973; Gordon et al. 1975; Kley et al. 1975; Lindholm et al. 1978). Table 2 summarizes the eight articles that report serum gonadotropin and testosterone levels in men with alcoholic liver disease. (Gonadotropins are pituitary hormones that regulate gonadal function.) All of these studies report reduced levels of testosterone in alcoholic cirrhotic men as compared with normal men.

Additional studies were performed in alcoholics without cirrhosis and in males with nonalcoholic cirrhosis (Bannister et al. 1987; Van Thiel et al. 1981). As a result of these studies, it became clear that alcohol itself was the principal cause of hypogonadism seen in alcoholic men, particularly those with advanced liver disease.

Studies done with animals confirmed these results, demonstrating that alcohol could cause testicular failure in the absence of alcohol-induced liver disease (Badr and Bartke 1974; Badr et al. 1977; Gavaler et al. 1980; Van Thiel et al. 1975, 1979; Cicero and Badger 1977). Moreover, alcohol reduced testosterone production by isolated rat testicular cells in the absence of any chemical produced by liver disease or by the metabolism of alcohol by the liver (Cobb et al. 1980).

Direct Effects of Alcohol on the Testis

When assessing testicular failure, the two functions of the testis--sperm production and testosterone production--must be examined independently.

The cells responsible for sperm production occupy 95 percent of the testicular volume. Therefore, failure of spermatogenesis (sperm production) may be characterized by testicular atrophy associated with oligospermia (decreased sperm production) or azoospermia (absence of sperm). In contrast, decreased production of steriod sex hormones (principally testosterone) is characterized by a loss of male secondary sex characteristics, impotence, diminished libido, and other symptoms, but usually not by an obvious reduction in testicular size.

Researchers have studied the effects of alcohol on both testicular functions. For example, isolated Leydig cells(1) are able to synthesize and secrete testosterone in response to gonadotropin stimulation. However, when the cells are exposed to alcohol at low concentrations (5.4 millimolar, roughly equivalent to a blood level of 0.25 milligram percent, the approximate result of five drinks), testosterone production is inhibited by as much as 44 percent. Acetaldehyde (the initial product of alcohol metabolism) is even more toxic to isolated Leydig cells than is alcohol (Van Thiel et al. 1983; Santucci et al. 1983). With respect to spermatogenesis, the testes of both alcoholic men and rats fed alcohol chronically show advanced injury to the germ cells of the seminiferous tubules, the site of sperm production within the testis (Gavaler and Van Thiel 1987).

Mechanisms of Testicular Injury

Alcohol administration has been shown to reduce in the testes the activity of enzymes crucial to the synthesis of steroid sex hormones (Cicero and Bell 1980; Johnston et al. 1981; Chiao and Van Thiel 1983). The administration of alcohol also alters the electrochemical balance (redox state) of the cell in such a way as to further inhibit testosterone-synthesizing enzymes (Chiao et al. 1981).