Show me the science: how estrogen reduction is impacting your metabolism (and what to do about)

Wendy Kohrt knows a thing or two about our estrogen: she’s been studying its impact on metabolism for 30 years. 

When she started out the common belief was that estrogen therapy was so effective that every menopausal woman should be on it – to the point that she had to justify the ethics of randomizing women to a placebo during her clinical trials. 

Then she saw the situation change “180 degrees” when the Women’s Health Initiative trials made for scary headlines (while being overblown and based on faulty methodology) – and we know what happened after that. 

(If you are still catching up, hormone therapy use dropped by 70 to 80 percent, and is still recovering) 

“I think the pendulum has swung back to the middle – women should be treated with estrogen therapy at the time of the menopause for the relief of menopausal symptoms,” she tells Hotflash inc. “But we still have much to learn.”

Also a professor of medicine in the geriatric medicine division at the University of Colorado Health Sciences Center, Denver, Dr Kohrt has conducted hundreds of research studies on the impact of loss of ovarian function on energy intake and output, adiposity and bone loss. 

Her work on body composition, fat patterning and the role of age and estrogen provide compelling evidence for the use of hormone therapy to prevent the impact of estrogen loss on reducing movement and exercise, increasing calorie consumption and body fat.

As Kohrt’s work continues to show, whether in mice or rats or humans, that the addition of estradiol appears to be a consistent, and wide-ranging, mitigating factor. 

One of the biggest challenges in her menopause-related work has been demonstrating that the changes observed are due to the hormonal impact of menopause, and not just aging. 

“Part of the problem is that the menopause is a process, not an event,” she says. “The changes happen over years, not weeks or months. It's really difficult to isolate out whether the effects of menopause are separate from the effects of aging that is taking place over those number of years.”

To address the age-versus-menopause issue, Dr Kohrt’s team in Colorado uses a medication that suppresses ovarian function, decreasing her study subject’s hormone levels to postmenopausal levels for a few months. 

“We've done three or four of these studies,” she says. “What we found is that even within just a few months, when we suppressed ovarian hormones, resting metabolic rate goes down.”

While the metabolic rate seen in the ovarian-suppressed women doesn’t go down a lot – 50 to 70 calories a day, or the equivalent of a half a piece of bread – it gets compounded when there is no corresponding calorie reduction or increase in movement and exercise. 

“Just that change alone could account for an increase in fat mass of one pound over about two to three months,” said Dr Kohrt. “It really is a fairly substantial disruption in energy balance that would promote weight gain.”

Another observation? The fat accumulation observed in ovarian-suppressed women was different – and more dangerous – leading Dr Kohrt’s team to see estradiol as important not only in regulating how much fat is stored during menopause, but where it is stored. 

“The fat tends to come on in the belly region and not right under the skin,” says Dr Kohrt. “It tends to accumulate behind the muscle wall around the vital organs. We call that visceral fat or intra-abdominal fat. The fat in that region has been associated with risk for certain chronic diseases, like heart disease, type 2 diabetes and hypertension.” 

While researchers don’t yet understand why or how that happens, the findings are a piece of a much-larger puzzle: why menopausal women seem to be at risk for the kinds of chronic diseases associated with abdominal obesity that they are protected from in a premenopausal state.

Exercise does mitigate some of the tendency to put on fat in the abdominal area during ovarian suppression, but not with the efficiency of estrogens, says Dr Kohrt. The studies done on rats and mice, which are extremely energetic creatures, “will just make you shake your head”, she adds. 

Menopause experiments involving mice or rats actually remove the ovaries, via an ovariectomy, while another group undergoes a “sham” surgery that leaves the ovaries in place. 

“Physical activity levels in the ovariectomized animals just drops dramatically,” says Dr Kohrt. “Not by 5 percent, 10 percent, 15 percent, more like 50 percent, 60 percent, 70 percent.”

Animals who have that estrogen added back, on the other hand, go right back to their running wheels and vigorous, pre-surgery activity levels. 

“This is another piece of evidence that estrogen regulates our energy balance,” says Dr Kohrt. “We're taking in more energy than we're burning and the result of that is weight gain.”

Dr Kohrt also told her NAMS colleagues about an emerging area indicating the impact follicle stimulating hormone (FSH) – long thought to be limited to regulating reproductive function – seems to have on metabolism. FSH tends to move in the opposite direction of estrogen, meaning it rises as estrogen declines during the menopause transition. 

One study involving ovary-removed mice found that when researchers blocked FSH with an FSH antibody, they prevented ovariectomy-related bone loss. Another study in animals found FSH antibodies prevented an increase in obesity, specifically fat deposition or fat accumulation in the abdominal region. 

That was a key finding in suggesting FSH might be much more important than previously thought in regulating both risk for osteoporosis and risk for obesity, says Dr Kohrt.

Her work now uses different approaches in animals to study the role of FSH in fat gain, bone loss and other consequences of menopause previously thought to be related to estrogen; research that will soon be expanded to involve women. 

“We haven't even considered the impact of trying to manipulate it after menopause as a way to minimize or prevent some of the menopause-related changes that occur,” she explains. “We are only going to learn this if we continue to take small steps until we can make that grand leap to saying what the impact of that would be.”

Wendy spoke to Hotflash inc in 2020, ahead of a presentation of her work to the North American Menopause Society Annual Meeting.