Testosterone Boosts Sexual Function in Men, Across the Board

Liam Davenport

July 13, 2016

Testosterone therapy improves sexual desire and activity across almost all domains in symptomatic older men with low libido and low testosterone levels, with responses linked to changes in both testosterone and estradiol levels, say US researchers.

The research, which was published online in the Journal of Clinical Endocrinology & Metabolism on June 29, is a further analysis of data from the Sexual Function Trial, which forms part of a coordinated set of seven double-blind, placebo-controlled studies in the Testosterone Trial.

As previously reported by Medscape Medical News, testosterone therapy in the Sexual Function Trial was associated with a significant increase in sexual activity, as determined by the Psychosexual Daily Questionnaire (PDQ) score, as well as in sexual desire and erectile function.

The current analysis, led by Glenn R Cunningham, MD, of Baylor College of Medicine and Baylor St Luke's Medical Center in Houston, Texas, takes a deeper dive and indicates that testosterone therapy improved 10 of the 12 domains of sexual activity on the PDQ, with the most notable impact on measures associated with libido.

Talking to Medscape Medical News, Dr Cunningham said: "What I think these studies have shown is that, even in older men who are testosterone deficient and who have decreased libido, testosterone treatment can be beneficial in terms of sexual function and not only in terms of libido but also in terms of erectile function and sexual activity."

However, he emphasized that the risks and benefits have to be weighed and age taken into consideration when contemplating treating a man with symptoms and low testosterone levels.

"In younger men you tend to have more potential for benefits than risks," he said. "As you get into middle age and older, then there's a greater potential for risk."

Unresolved Issues, but Testosterone Good for Low Libido, if Levels Are Low

Dr Cunningham noted that the "two major unresolved issues" are whether testosterone could increase the potential for an occult prostate cancer to become a clinical prostate cancer and whether it could increase cardiovascular risk.

"Neither of those are proven, but because we know androgens have effect on parameters that are relevant here, we need to have clinical-trial data to resolve that," he said.

Approached for comment, Bradley Anawalt, MD, professor, department of medicine and chief of medicine, University of Washington Medical Center, Seattle, said that the current findings "buttress" those of the original study by revealing a "consistent effect" of testosterone therapy across all the domains of sexual function.

He added: "This study suggests that their initial findings were not a fluke, they're real."

Dr Anawalt highlighted that the "other important finding" is that increases in total and free testosterone and estradiol levels were associated with improvements in sexual activity and desire. He said that the role of estradiol in sexual function "is now getting to be more of a consistent story."

Based on these results, he believes that testosterone therapy is ready to be used for treating low libido.

"If you have a man in your clinic, be it in Europe of the United States, and he comes in with a primary complaint of decreased libido and decreased overall sexual function and has a low testosterone concentration on a reproducible basis, giving testosterone to that man is a sensible thing to do."

However, Dr Anawalt noted that the treatment is "specifically restricted to the category of man who comes in and has complaints that he's just not as interested in sex as he used to be and who has low testosterone concentrations," as it will not work in men who have reduced desire but normal testosterone levels or in those who cannot achieve an erection.

HRT for Men: Study Results Show Improvements in All Sex Activity Domains

The study took place in 12 academic medical centers in the United States and involved 470 men aged ≥ 65 years who had low libido, an average testosterone level of < 275 ng/dL, and a partner willing to have sexual intercourse at least twice a month.

The men were assigned to use either a 1% testosterone gel at an initial dose of 5 g daily or a placebo gel for 1 year, with sexual function assessed using the PDQ, the Derogatis Interview for Sexual Function, and the International Index of Erectile Function every 3 months.

There were few differences in baseline characteristics between men treated with testosterone and those given placebo. Overall, more than 60% of the participants were obese, approximately 33% had diabetes, and over 70% had hypertension. Fewer than 11% of men were using a phosphodiesterase type 5 inhibitor.

The team found that testosterone treatment increased serum total and free testosterone and estradiol levels up to the mid-normal range for healthy men aged 19 to 40 years, while placebo had no effect.

Participants treated with testosterone experienced significant improvements vs placebo on 10 of the 12 domains of sexual activity on the PDQ: sexual daydreams; anticipation of sex; sexual interaction with a partner; flirting by subject; orgasm; ejaculation; intercourse; masturbation; spontaneous erection at night; and sexual arousal erection (P < .001 to .026). The treatment effect size ranged from 0.02 for intercourse to 0.10 for sexual daydreams.

There were no significant improvements associated with testosterone therapy on the domains of flirting by others and spontaneous erections by day. The frequency at which the 12 activities occurred varied widely, ranging from 5% to 40% of the days.

There were nominally significant interactions between some baseline characteristics and the effect of testosterone therapy. For example, increased alcohol intake was associated with a greater effect of testosterone on sexual desire and activity. In contrast, a history of stroke and coronary artery disease and higher prostate symptom and Positive and Negative Affect Scale scores were associated with a lower effect of testosterone.

The magnitude of changes in total and free testosterone and estradiol levels in the blood was significantly associated with the degree of improvements in sexual desire and activity, but not with erectile function. Interestingly, only increments in estradiol levels were associated with improvements in orgasmic function.

"I'd Give My Eyeteeth to Have One or Two More Orgasms a Month"

Dr Anawalt commented that "there's going to be a big fuss about this study, and the big fuss" will center on how the results are interpreted. That, he said, hinges on whether or not they are considered significant in terms of the impact of testosterone therapy on individuals' lives.

Taking orgasm as an example, Dr Anawalt said that the bar graph showing the impact of testosterone vs placebo "suggests that, without testosterone, men were having an orgasm about every 14 days," or approximately 7% of the time.

He added: "If you had testosterone, it was about every 8 days, so simple math: twice a month without and about four times a month with testosterone. So, at least one or more orgasms a month, maybe two."

Dr Anawalt said that some experts would "pooh-pooh" the findings and say: "These are little tiny, statistically significant changes and it's not clinically significant." However, he argued that many men would say: "Never mind that, I'd give my eyeteeth to have one or two more orgasms a month."

He continued: "I think the latter is correct. If you look, even in Europe, all of the advertisements and all the products being sold to increase the chances of having sex and an orgasm, it seems pretty clear to me that people are willing to do a lot for one or two extra orgasms a month."

He concluded that the figure for orgasm is "quite informative in terms of talking about this controversy," adding: "You can easily paint it as something that is not very significant, or you turn it around and say: 'Well, let's be real here. These changes numerically might not be very large, but they are plenty of motivation for the average guy out there.' "

The Testosterone Trial was supported by a grant from the National Institute on Aging and National Institutes of Health, supplemented by funds from the National Heart, Lung, and Blood Institute, National Institute of Neurological Diseases and Stroke, and National Institute of Child Health and Human Development. AbbVie (formerly Solvay and Abbott Laboratories) provided funding, AndroGel, and placebo gel. Dr Cunningham has served as a consultant to AbbVie, Apricus, Besins, Clarus Therapeutics, Endo Pharma, Ferring, Lilly, Pfizer, and Repros Therapeutics, and he has served as an expert witness for Repros Therapeutics and Solvay. He has received research support from Ardana and Unimed. Disclosures for the coauthors are listed in the article.

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J Clin Endocrinol Metab. Published online June 29, 2016. Abstract


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