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It is well known that women have a "biological clock" associated with declining fertility, increasing risk for fetal birth defects, and altered hormone levels. Now an increasing body of scientific evidence points to the existence of a similar male biological clock, according to a retrospective review article by NewYork-Presbyterian Hospital and Columbia University Medical Center researchers published in the Nov. 15 Journal of the American Medical Association (JAMA). Conditions associated with the male phenomenon include declining fertility, lowered testosterone levels, diabetes, heart disease, depression, erectile dysfunction (ED) and an increased risk of fetal birth defects.

"Similar to women, aging is associated with declines in sex hormone levels in men. Testosterone decrease is not as steep or as sudden as that associated with estrogen declines during menopause in women, but its effects can be significant," says Dr. Harry Fisch, the study's senior author and director of the Male Reproductive Center and director of urologic microsurgery at NewYork-Presbyterian/Columbia, and professor of clinical urology at Columbia University College of Physicians and Surgeons. Dr. Fisch is also the author of The Male Biological Clock (Free Press), published earlier this year.

Low testosterone level (hypogonadism) affects between two million and four million American men. Symptoms include decreased muscle mass and bone mineral density; decreased libido and energy; obesity; insulin resistance; and mental and emotional problems. Other associated medical conditions and specific findings chronicled in Dr. Fisch's article include:

Male Infertility. Male infertility increases with the man's age. Men older than 35 are twice as likely to be infertile (defined as the inability to initiate a pregnancy within 12 months) compared to men younger than 25.

Birth Defects. As with advanced maternal age, advanced paternal age is associated with an increased incidence of birth defects due to decreased genetic quality of sperm. Men 40 and older are nearly six times more likely to have offspring with autism than men younger than 30, even after controlling for maternal age and other variables. Other defects associated with elevated paternal age include schizophrenia, Down syndrome and genetic abnormalities.

Type 2 Diabetes and Metabolic Syndrome. Both Type 2 diabetes and metabolic syndrome (which involves pre-diabetes symptoms as well as cardiovascular risk factors) are strongly associated with below-normal levels of testosterone. Of men aged 40 to 49 with Type 2 diabetes, 40 percent had decreased testosterone; the rate was nearly 55 percent among men in their 70s.

Erectile Dysfunction (ED)-Related Conditions. Broadly speaking, ED is strongly related to age-related biological changes and, hence, the male biological clock is also implicated in these other chronic, frequently progressive, and disruptive conditions:

Cardiovascular Disease. Prevalence of ED is significantly higher among patients being treated for heart disease and hypertension. Treatments for hypertension may contribute to erectile dysfunction, which may help explain the increased incidence of ED in these patients. However, the reverse relationship is also true: ED should be considered a marker for hypertension and other cardiovascular complications.

Depression. Depression may both contribute to and link erectile dysfunction and cardiovascular disease. Erectile dysfunction is associated with well-established negative psychological effects, primarily depression and anxiety. Furthermore, patients with ED who are depressed are more likely to develop cardiovascular disease.

Mortality. In one study, men with low testosterone had a mortality rate of 35 percent during the eight-year study period compared with a mortality rate of only 20 percent among men with normal testosterone levels. This trend persisted even after controlling for all reasonable variables in the study population.

The most common available treatment for hypogonadism is testosterone replacement therapy.

The study reports that prescription testosterone use in the United States has increased significantly in recent years with approximately 2.3 million prescriptions written in 2005; this represents a 50-percent increase from 2001 and a 210-precent increase from 1999. (In another ill-advised practice, testosterone therapy is prescribed "off label" for physical enhancement, such as for boosting muscle mass or "energy" in otherwise healthy men.)

"An improved understanding of the associated cellular and biochemical mechanisms of 'gonadal' aging is needed so that safe and effective ways to delay this process, or, in effect, 'rewind' the clock, might be possible," says Dr. Fisch.

The article's co-authors include Dr. Marianne Legato, founder and director of the Partnership for Gender Specific Medicine at NewYork-Presbyterian/Columbia and professor of clinical medicine at Columbia University College of Physicians and Surgeons; and Dr. Benjamin H. Lewis, cardiologist at NewYork-Presbyterian/Columbia and associate clinical professor of medicine at Columbia University College of Physicians and Surgeons.

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NewYork-Presbyterian Hospital

NewYork-Presbyterian Hospital – based in New York City – is the nation's largest not-for-profit, non-sectarian hospital, with 2,224 beds. It provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine at five major centers: NewYork-Presbyterian Hospital/Weill Cornell Medical Center, NewYork-Presbyterian Hospital/Columbia University Medical Center, Morgan Stanley Children's Hospital of NewYork-Presbyterian, NewYork-Presbyterian Hospital/Allen Pavilion and NewYork-Presbyterian Hospital/Westchester Division. One of the largest and most comprehensive health-care institutions in the world, the Hospital is committed to excellence in patient care, research, education and community service. It ranks sixth on U.S.News & World Report's guide to "America's Best Hospitals," has the greatest number of physicians listed in New York magazine's "Best Doctors" issue, and is included among Solucient's top 15 major teaching hospitals. The Hospital has academic affiliations with two of the nation's leading medical colleges: Joan and Sanford I. Weill Medical College of Cornell University and Columbia University College of Physicians and Surgeons.

Columbia University Medical Center

Columbia University Medical Center provides international leadership in pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, nurses, dentists, and public health professionals at the College of Physicians and Surgeons, the College of Dental Medicine, the School of Nursing, the Mailman School of Public Health, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. For more information, visit www.cumc.columbia.edu.