Infertility in Men Tied to Heart Disease, Chronic Conditions

Tara Haelle

December 07, 2015

Men with infertility have a higher risk for a variety of other chronic medical conditions, including diabetes, heart disease, alcohol abuse, and drug abuse, according to a retrospective cohort study published online December 7 in Fertility and Sterility.

"The results suggest that male factor infertility has more than just reproductive implications," write Michael Eisenberg, MD, assistant professor of urology and director of male reproductive medicine and surgery at Stanford University School of Medicine in California, and colleagues.

"Because 20%–25% of infertile couples bypass a male evaluation, a lost opportunity to improve men's health should be revisited," they write. "Further evaluation of the man should be considered beyond optimizing and obtaining sperm, including continued surveillance of the infertile male in the years after reproductive efforts cease."

Understanding the causes of the increased risks for health conditions may also lead to prevention strategies such as improved diet and exercise, the authors add.

The researchers used insurance claims data from 2001 to 2008 from the Truven Health MarketScan to identify more than 115,000 patients for the study population. They compared outcomes among 13,027 men diagnosed with male factor infertility (average age, 33 years), with outcomes among 23,860 men (average age, 33 years) who received semen or infertility testing and with outcomes among 79,099 men who had received vasectomies.

The authors looked for 16 conditions: hypertension, diabetes, hyperlipidemia, renal disease, chronic pulmonary disease, liver disease, depression, peripheral vascular disease, cerebrovascular disease, ischemic heart disease, other heart disease, injury, alcohol abuse, drug abuse, anxiety disorders, and bipolar disorder.

Importantly, the researchers excluded all men diagnosed with underlying conditions at least 1 year before and 1 year after their fertility test or vasectomy, thereby reducing the likelihood of reverse causality because the men were healthy at baseline.

The men with infertility had higher rates of obesity and smoking, but even after adjustment for these covariates and for age, follow-up time, and healthcare use, men with infertility had a higher risk for multiple conditions compared with vasectomized men or those receiving only fertility testing. Specifically, compared with the men who received fertility testing, men with infertility had a 30% increased risk for diabetes (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.10 - 1.53), a 48% increased risk for ischemic heart disease (HR, 1.48; 95% CI, 1.19 - 1.84) and for alcohol abuse (95% CI, 1.07 - 2.05), a 67% increased risk for drug abuse (HR, 1.67; 95% CI, 1.06 - 2.63), and a 19% increased risk for depression (HR, 1.19; 95% CI, 1.04 - 1.36).

Compared with men who received vasectomies, those with infertility had a 9% higher risk for hypertension (HR, 1.09; 95% CI, 1.02 - 1.17), a 14% greater risk for hyperlipidemia (HR, 1.14; 95% CI, 1.07 - 1.22), a 41% greater risk for ischemic heart disease (HR, 1.41; 95% CI, 1.19-1.67), and a 16% greater risk for other heart disease (HR, 1.16; 95% CI, 1.04 - 1.29). Further, men with infertility, compared with vasectomized men, had an 81% greater risk for diabetes (HR, 1.81; 95% CI, 1.57 - 2.08), a 60% greater risk for renal disease (HR, 1.60; 95% CI, 1.14 - 2.24), a 53% greater risk for liver disease (HR, 1.53; 95% CI, 1.31 - 1.80), and a 52% greater risk for peripheral vascular disorders (HR, 1.52; 95% CI, 1.12 - 2.07).

The greatest risk for renal disease occurred among men with azoospermia (zero sperm counts, the most severe form of male infertility), whose risk was more than twice that of men who received only fertility testing (HR, 2.26; 95% CI, 1.20 - 4.27). Men with azoospermia also had nearly double the risk for alcohol abuse compared with men only tested (HR, 1.94; 95% CI, 1.11 - 3.39).

"The link between male factor infertility and future adverse health remains uncertain, although several convincing explanations have been proposed," the authors write. "[I]nvestigators have hypothesized that fetal exposures may lead to adverse reproductive and somatic health in adulthood."

Another possibility relates to low levels of testosterone in men with infertility, they note.

"Because hypogonadism is a risk factor for cardiovascular disease and mortality, such an explanation may link infertility to cardiovascular disease," they write.

"Although infertility may be a marker of diminished fitness, which may accelerate the development of impaired health in the future, it may also occur as a consequence of current health, clinical or subclinical."

Dr Eisenberg holds stock in and is an advisor to Sandstone Diagnostics. The other authors have disclosed no relevant financial relationships.

Fertil Steril. Published online December 7, 2015. Abstract

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