Is There a Relationship Between Sex Hormones and Erectile Dysfunction? Results From the Massachusetts Male Aging Study Varant Kupelian,* Ridwan Shabsigh,† Thomas G. Travison, Stephanie T. Page, Andre B. Araujo and John B. McKinlay From the New England Research Institutes, Watertown, Massachusetts (VK, TGT, ABA, JBM), Department of Urology, Columbia University, New York, New York (RS), and the University of Washington, Seattle, Washington (STP) Purpose: The prevalence of erectile dysfunction increases as men age. Simultaneously, age related changes occur in male endocrine functioning. We examined the association between erectile dysfunction and total testosterone, bioavailable testosterone, sex hormone-binding globulin and luteinizing hormone. Materials and Methods: Data were obtained from the Massachusetts Male Aging Study, a population based cohort study of 1,709 men. Self-reported erectile dysfunction was dichotomized as moderate or severe vs none or mild. Odds ratios and 95% CI were used to assess the association between sex hormone levels and erectile dysfunction. Multiple logistic regression models were used to adjust for potential confounders including age, body mass index, partner availability, phosphodiesterase type 5 inhibitor use, depression, diabetes and heart disease. Results: Using data from the most recent followup, analyses were conducted on 625 men with complete data. A moderate decrease in erectile dysfunction risk was observed with increasing total testosterone and bioavailable testosterone levels. However, this effect was not apparent after controlling for potential confounders. Increased luteinizing hormone levels (8 IU/l or greater) were associated with a higher risk of erectile dysfunction (adjusted OR 2.91, 95% CI 1.55–5.48) compared to luteinizing hormone levels less than 6 IU/l. A significant interaction between luteinizing hormone and total testosterone levels showed that increased testosterone levels were associated with a decrease in risk of erectile dysfunction among men with luteinizing hormone levels greater than 6 IU/l. Conclusions: In this large population based cohort of older men we found no association among total testosterone, bioavailable testosterone, sex hormone-binding globulin and erectile dysfunction. Testosterone levels were associated with a decrease in risk of erectile dysfunction only in men with increased luteinizing hormone levels. Key Words: impotence, gonadal steroid hormones, aging, epidemiology T he increase in incidence of ED with age and the pro- gressive decrease in androgen levels in mid to late adulthood are well documented. 1–3 However, a consis- tent correlation between T levels and ED has not been established. 4,5 Some studies of T replacement in hypogo- nadal men have reported improvements in erectile func- tion. 6,7 However, a dose-response effect was not seen at different T levels within the normal range 8 or when raising T levels above the normal range. 9 A recent meta-analysis of 17 randomized placebo controlled trials of the effect of T on sexual function shows that while T treatment improved sexual function in hypogonadal men, T supplementation had no effect on erectile function in eugonadal men. 10 The role of androgens in erectile function remains controversial. The purpose of this study was to determine whether there is a relationship between sex hormone levels (total T, free T, SHBG and LH) and erectile dysfunction using data from the Massachusetts Male Aging Study, a large prospective cohort of men followed for more than 15 years. MATERIALS AND METHODS The Massachusetts Male Aging Study is a population based cohort study of aging men observed at 3 points (T 1 —1987 to 1989, T 2 —1995 to 1997, T 3 —2002 to 2004). The sampling design and field protocol have been described previously. 11 Men 40 to 70 years old were randomly selected from 11 cities and towns in the Boston, Massachusetts area. Men in older age groups were over sampled to provide approximately equal proportions in each decade (40 to 49, 50 to 59, 60 to 70 years old). At baseline (T 1 ) a total of 1,709 men (52% of those eligible) were enrolled in the study. A telephone survey of nonrespondents (206) revealed that they were similar to respondents in general health and prevalence of chronic diseases. At the first followup phase (T 2 ) 1,596 of the original 1,709 men were eligible for study and 1,156 men completed aT 2 interview (72% response rate). At the second followup phase (T 3 ) 1,351 men were eligible of which 853 were inter- viewed (63% response rate). MMAS received institutional review board approval and all participants gave written informed consent. Submitted for publication February 21, 2006. Supported by Grant AG04763 from the National Institute on Ag- ing, and Grants DK51345 and DK44995 from the National Institute of Diabetes and Digestive and Kidney Diseases. * Correspondence: 9 Galen St., Watertown, Massachusetts 02472 (telephone: 617-923-7747 ext. 512; FAX: 617-924-0968; e-mail: Jmckinlay@neriscience.com). † Financial interest and/or other relationship with Pfizer, Solvay, Indevus Pharmaceuticals, Lilly-Icos, American Medical Systems, Johnson & Johnson, Bayer/GSK and Boehringer Ingelheim. Sexual Function/Infertility 0022-5347/06/1766-2584/0 Vol. 176, 2584-2588, December 2006 THE JOURNAL OF UROLOGY ® Printed in U.S.A. Copyright © 2006 by AMERICAN UROLOGICAL ASSOCIATION DOI:10.1016/j.juro.2006.08.020 2584