Researchers have discovered that, just as women go through menopause due to a dramatic decrease in estrogen production, middle-aged men undergo estrogen-related changes in body composition and sexual function.
The study, published in The New England Journal of Medicine, was conducted by researchers at Massachusetts General Hospital (MGH).
The researchers say that traditionally, when a diagnosis of male hypogonadism has been made - a drop in reproductive hormone levels that are high enough to cause physical symptoms - it has only been based on blood testosterone levels.
However, they say there has been little understanding of the levels of testosterone needed to support certain functions.
According to the study authors, a small proportion of the testosterone made by men is usually converted into estrogen by aromatase - a type of enzyme. The higher the testosterone level in a man, the more testosterone is converted into estrogen.
Researchers have found that low estrogen levels in men can trigger weight gain and adverse changes to their sexual functions.
They add that since men with low testosterone levels also have low estrogen levels, this makes it unclear as to which hormones support certain functions.
Therefore, the researchers wanted to determine the levels of hormone deficiency at which changes occur in men, and whether these are due to low levels of testosterone, estrogen or both.
For this study, the research team enrolled two groups of approximately 150 men aged between 20 and 50 who had normal reproductive functions.
The researchers assigned one group of men to receive daily doses of testosterone gel at one of four dosage levels, or a placebo gel for a period of 16 weeks.
Men in the second group were required to have the same testosterone doses but alongside an aromatase inhibitor, which was responsible for suppressing the conversion of testosterone into estrogen.
All men had their body composition and leg strength assessed at the beginning of the study and were required to complete monthly questionnaires and blood tests throughout the study period.
Aspects of testosterone deficiency determined by estrogen
Results of the study revealed that men who did not have estrogen production blocked showed increases in body fat similar to what would be seen at a mild level of testosterone deficiency.
When testosterone levels became low, this triggered decreases in lean body mass, the size of the thigh muscle and leg strength.
The sexual desire of the men decreased in line with each drop in testosterone levels, while erectile dysfunction did not occur until testosterone levels were very low.
Men who had their estrogen production blocked showed increases in fat at all testosterone dosage levels, as well as adverse changes in their in sexual function.
Joel Finklestein, of the Endocrine Unit at MGH and associate professor of medicine at Harvard Medical School, says:
"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."
"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."
Potential testosterone replacement therapy
The researchers note that in this present study, they have artificially induced a type of hormone deficiency commonly seen in aging men in order to provide a controlled model. They plan to conduct a follow-up study in older men to confirm the accuracy of this model.
They note that the findings of this study showing the effect of estrogen suggests that forms of testosterone used for therapy "should be capable of being aromatized into estrogen."
"We also need to look into how testosterone replacement therapy would affect prostate health - both prostate cancer and the prostate enlargement that causes unpleasant symptoms in many older men - and heart disease," says Finklestein.
"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."