Thursday, January 15, 2009

Older men are having children, but the reality of a male biological clock makes this trend worrisome by Harry Fisch MD

Older men are having children, but the reality of a male biological clock makes this trend worrisome
Feature ArticlePublish date: Jan 15, 2009
By: Harry Fisch, MD
Source: Geriatrics

Dr Fisch is Professor of Clinical Urology, Department of Urology, Columbia University College of Physicians and Surgeons, Columbia University Medical Center, New York City.

Disclosure: The author states that he has no financial relationship with any manufacturers in this area of medicine.


Couples are waiting longer to have children, and advances in reproductive technology are allowing older men and women to consider having children. The lack of appreciation among both medical professionals and the lay public for the reality of a male biological clock makes these trends worrisome. The age-related changes associated with the male biological clock affect sperm quality, fertility, hormone levels, libido, erectile function, and a host of non-reproductive physiological issues. This article focuses on the potentially adverse effects of the male biological clock on fertility in older men. Advanced paternal age increases the risk for spontaneous abortion as well as genetic abnormalities in offspring due to multiple factors, including DNA damage from abnormal apoptosis and reactive oxygen species. Increased paternal age is also associated with a decrease in semen volume, percentage of normal sperm, and sperm motility. Older men considering parenthood should have a thorough history and physical examination focused on their sexual and reproductive capacity. Such examination should entail disclosure of any sexual dysfunction and the use of medications, drugs, or lifestyle factors that might impair fertility or sexual response. Older men should also be counseled regarding the effects of paternal age on spermatogenesis and pregnancy.

Fisch H. The aging male and his biological clock. Geriatrics. 2009;64(1):14-17.

Keywords: apoptosis, hypogonadism, male biological clock, male infertility, paternal age, spermatogenesis, testosterone

The phrase "biological clock" commonly refers to the declining fertility, increasing risk for fetal birth defects, and altered hormone levels experienced by women as they age. Abundant scientific evidence suggests that men also have a biological clock.1,2 The hormonal and physiological effects of the male clock are linked with testosterone and fertility declines, as well as pregnancy loss and an increased risk of birth defects.3 In this article, we review the effects of the male biological clock, and the association between advanced paternal age and decreased spermatogenesis, pregnancy rates, and birth outcomes.

Male testosterone levels (both total and free) decline roughly 1% per year after age 30.4 The rate of decline in one study4 was not significantly different between healthy men and those with chronic illnesses or multiple comorbidities. This decline can shift men whose testosterone levels are in the low end of the normal spectrum to levels considered below-normal, or hypogonadal (testosterone <325 ng/mL) as they age. An estimated 2 to 4 million men in the United States fall in this category, either from age-related declines, illness, injury, or congenital conditions.5 The population of hypogonadal men is increasing due both to the aging of the general population and unknown factors that appear to be suppressing the average levels of testosterone in more recent birth cohorts.6 The increasing prevalence of abnormally low testosterone levels in elderly men was demonstrated in the Baltimore Longitudinal Study on Aging, which determined that hypogonadal testosterone levels were present in approximately 20% of men over 60, 30% over 70, and 50% over 80 years of age.7

Sub-normal testosterone levels are associated not only with decrements in fertility and sexual response, but also a wide range of other health problems such as declines in muscle mass/strength, energy levels, and cognitive function, as well as increased incidence of weight gain (particularly central adiposity), type 2 diabetes, the metabolic syndrome, and cardiovascular disease. Testosterone replacement therapy to address the wide range of health problems related to hypogonadism is becoming increasingly popular. Delivery via gels or transdermal patches can result in physiologically normal levels of testosterone, which is preferable to the spiky levels obtained via testosterone injections. Oral formulations are under development but none have progressed beyond the clinical trial phase. Fears that testosterone replacement therapy may promote the growth of prostate carcinomas has abated in light of findings from several studies that find no such link.8

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