A study published in the September 12 issue of New England Journal of Medicine (NEJM) has caused quite a stir. Since the mainstream press got hold of this story, I’ve been flooded with questions from concerned men.
The gist of the study: low testosterone may not always be the reason behind standard male menopause (andropause) symptoms like fading libido, fat gain, muscle loss and low energy. It could, in fact (say these researchers and the journalists covering the story) be low estrogen. In particular, the study found that too little estrogen appeared to contribute to fat gain in these middle-aged male subjects.
Within hours of the stories being published in the New York Times and the LA Times, the questions and concerns started rolling in from the men I treat:
“What does this mean?”
“Maybe I can’t lose this weight because my estrogen is too low!”
“Hey! Doc! Do I need more estrogen?”
Whoa there, everybody!
Take a deep breath, fellas.
The information in this study is nothing new. We’ve known for a long time that men need a little bit of estrogen, and that if we drop it down to nothing, there are negative consequences.
Let’s start at the foundation.
Moving testosterone levels into an optimal range is a highly individualized part of what I do for my male patients. There’s testing and analysis of symptoms to ensure that the man might actually benefit from testosterone therapy. If we decide it’s worth a try, we go through a process of trial and error whereby we follow one of my guiding principles: start low and build slow until we find just the right dose.
If I talk about estrogen with a male patient, we usually talk about the potential harm too-high estrogen can do. As a man ages, his estrogen levels tend to rise relative to testosterone, which can then create weight gain, irritability, prostate problems, and low libido. If we choose to augment his T levels, we have to also ensure that we aren’t sending estrogen levels too high via testosterone therapy.
How could giving T – the “male” hormone – cause estrogens to rise? It all goes back to an enzyme called aromatase, which transforms testosterone into estrogens.
High aromatase can mean T replacement = an unwanted boost in estrogen levels. So, if I give a man T and his estrogen levels go up (as evidenced by symptoms or via testing), I know he needs an aromatase inhibitor to ensure that T we administer doesn’t go that route in excess.
On the other hand: we don’t want estrogen to be too low, either. Men’s bodies require small amounts of estrogen for building bone. And it’s true that for men, having inadequate estrogen in the body can lead to fat gain.
Here’s the key to understanding the link between estrogen and excess fat gain:
Estrogen is required for the activation of testosterone receptors.
Very low estrogens = the disappearance of some T receptors.
This means that when estrogens flatline, testosterone can’t bind to enough receptors to trigger the cellular responses that allow it to impact the body.
If receptor sites are inadequate, the body could be absolutely flooded with hormone and it won’t do a thing. A plane with all its seats filled can’t fit any more passengers; a body with all its testosterone receptors occupied can’t respond to any additional testosterone.
So: yes, men’s bodies do require a small amount of estrogen. Too much is bad. So is too little. Too-high estrogens will make men fat; so will too-low estrogens. This is not new news. We’ve known this since the early 2000s, when studies on this topic first came out.
It’s not uncommon for a man to come into my practice with very low estrogens, and if that’s the case, we usually give testosterone. Then, their bodies start to produce more estrogens through aromatization. If estrogens rise too high, we can try a small dose of aromatase inhibitor or a gentler natural inhibitor called indole-3-carbinol, which is derived from cruciferous vegetables.
This is the kind of complexity that gets swept under the rug when folks try to over-simplify the art and science of bioidentical hormone therapy. Variables like receptor sensitivity and the complex interactions between hormones like estrogen, progesterone and testosterone are not easy for laypeople—even LA Times science writers—to understand.
Echoing my sentiment on the study is Dr Ed Friedman, an expert on estradiol and testosterone in men, and author of the book, “The New Testosterone Treatment.” According to Dr. Friedman, the NEJM study “showed that when both testosterone levels and estradiol levels rose from low levels, body fat decreased. Logically, this could have been because either testosterone decreases body fat, estradiol decreases body fat, or both do. The researchers tested a variety of physiological levels of testosterone while holding the level of estradiol constant and demonstrated that increasing testosterone levels decreases body fat. However, the researchers failed to do the corresponding experiment in which they would test a variety of physiological levels of estradiol while holding the level of testosterone constant, so there is insufficient data to show exactly what the relationship is between estradiol and body fat.”
I’m glad this story came out, though, because it’s giving me a chance to further educate my patients.
Photo credit: livescience.com