Menopause in women is attributed to a drastic decline in estrogen production while symptoms commonly seen in middle aged men, like changes in body composition, energy level, strength and sexual function, are commonly attributed to a decrease in testosterone production. A new study by Massachusetts General Hospital (MGH) researchers, however, has found evidence that insufficient estrogen production could be partially responsible for at least some of the symptoms men experience as well.

“This study establishes testosterone levels at which various physiological functions start to become impaired, which may help provide a rationale for determining which men should be treated with testosterone supplements,” says Joel Finkelstein, MD, of the MGH Endocrine Unit, corresponding author of the study in the New England Journal of Medicine. “But the biggest surprise was that some of the symptoms routinely attributed to testosterone deficiency are actually partially or almost exclusively caused by the decline in estrogens that is an inseparable result of lower testosterone levels.”

Usually, a male hypogonadism diagnosis is based on the measurement of testosterone levels in the blood. Although the condition is now being diagnosed more frequently, according the the authors, there has been little understanding of the testosterone levels needed to support specific functions.

While testosterone has a direct effect on physical functions, a small portion is typically converted to estrogen by an enzyme called aromatase. The higher the testosterone level is, the more of it that is converted to estrogen. Any drop in testosterone means there is less to be converted to estrogen. This makes it unclear which hormones support what functions. The research team at MGH was determined to find the level of hormone deficiencies at which symptoms start to surface and if those changes could be attributed to decreased levels of testosterone, estrogen or both.

The study included two groups of men with normal reproductive function, between the ages of 20 and 50. All participants were first treated with a drug to suppress normal production of all reproductive hormones. Men in one group were randomly chosen to receive a daily dose of testosterone gel at one of four dosage sizes or a placebo for a duration of 16 weeks. Men in the other group received the same dose, but were also given an aromatase inhibitor to suppress the conversion to estrogen.

In the end, the results showed that testosterone regulates lean body mass, muscle size and strength, while estrogen regulates fat accumulation. Sexual function was found to be regulated by both hormones.

“We also need to look into how testosterone replacement therapy would effect prostate health – both prostate cancer and the prostate enlargement that causes unpleasant symptoms in many older men – and heart disease,” says Finkelstein, who is an associate professor of Medicine at Harvard Medical School. “In light of what the Women’s Health Initiative discovered about the unexpected effects of estrogen replacement therapy in women, we need a Men’s Health Initiative to investigate those questions before large-scale testosterone replacement can be recommended.”