Hormonal Shifts May Intensify Obesity’s Effects in Women

Key takeaways:

• Obesity can have a greater impact on women during times of hormonal transition.
• Several biological influences contribute to obesity in women.

BOSTON — Obesity affects women differently than men, and losing weight can benefit women at any point in life, a speaker said at the Cardiometabolic Health Congress Women’s Cardiometabolic Health and Wellness Masterclass.

“Obesity is a disease. It affects women during the periods of hormonal change more because of the way those hormone changes interact with the hormones that go to the brain and regulate energy balance,” Healio | Endocrine Today Editorial Board Member Caroline M. Apovian, MD, FACN, FACP, FTOS, DABOM, professor of medicine at Harvard Medical School and inaugural director of the Combined MGB Weight Center at Mass General Brigham, said during a presentation. “It’s very important to understand that.”

Apovian said obesity prevalence among U.S. women rose from 25.4% to 41.9%, while severe obesity increased from 3.9% to 11.5% over the same period.

“There is a 37% reduction in mortality with metabolic bariatric surgery” in patients with obesity, she said. “We do only 250,000 procedures in the United States for 14 million people with a BMI over 40. If you said that about any other disease, you would say this is negligence. Because we still have a stigma, we’re not doing it.”

Biological factors contributing to obesity

Apovian said many biological factors contribute to obesity in women, including genetic influences, metabolic factors, hypothalamic regulation of food intake, neuroendocrine factors that affect that regulation, and environmental factors.

“The hypothalamic regulation of food intake is very important because those neuroendocrine factors, the changes in the hormonal milieu that happens in puberty during the fertility years and in menopause, affect the hypothalamic regulation of food intake,” she said. “And so in this environment, women are more predisposed to gaining weight during those periods.”

How much weight loss a woman needs depends on which metabolic risk factors must be controlled, Apovian said.

“To reduce intra-abdominal adipose tissue volume and cellular biology and reduce the inflammation, you need quite a bit of weight loss, over 15%,” she said. “But to just restore beta-cell function and improve liver insulin sensitivity, you only need 5%. What do you need to get to reduce hyperglycemia, high blood pressure? 5%. What do you need to prevent diabetes, fatty liver disease, dyslipidemia, and polyendocrine metabolic ovarian syndrome? You need a little bit more, 5% to 10%. Cardiovascular disease, the SELECT trial showed a reduction in major adverse CV events with a 9% weight loss in people who already had one cardiovascular event. Reduction in metabolic dysfunction-associated steatohepatitis or obstructive sleep apnea, you need more like 10% to 15%. And remission of diabetes, reduction in CV mortality, and heart failure with preserved ejection fraction, where do you see that? You see that with tirzepatide (Zepbound, Eli Lilly), one of our better GLP-1s, and metabolic bariatric surgery.”

Several stages of a woman’s life are important in the development of obesity, and puberty is one of the earliest, Apovian said.

“There are many hypotheses linking obesity, insulin resistance and adipokine secretion to timing [of puberty] and it seems that from the studies, increased adiposity in girls is associated with earlier onset of puberty and age of menarche, and this has happened over the past 50 years, that girls are now hitting puberty earlier than years ago, and that is likely related to fat storage,” she said.

Obesity also appears to be linked with infertility, Apovian said.

Adverse effects on female health

“Obesity definitely has adverse effects on reproduction, ovulatory function and menstrual function,” she said. “For example, for each BMI point greater than 29 [kg/m²], the probability of spontaneous conception decreased linearly.”

Obesity is also associated with a greater risk of poor maternal and fetal outcomes during pregnancy, and it can remain an issue after childbirth, Apovian said.

“Many women do not lose their pregnancy weight completely after they give birth because of stressors, work and family stress, and they retain that weight into the next pregnancy, and then we end up seeing them in our centers with menopause where they’ve gained between 20 lb and 50 lb, or even more,” she said.

Menopause brings additional changes that can contribute to weight gain and higher cardiometabolic risk, Apovian said.

“At menopause in midlife, women tend to gain weight, and the weight gain is not directly related to lack of estrogen,” she said. “The body composition changes are directly related to the lack of estrogen. You end up with more of an android pattern. There is more visceral body fat deposition and less subcutaneous fat. That’s why the risk in postmenopausal women for CVD is higher than younger women. Also, there are mood changes related to menopause because of the change in the hormonal milieu, and there’s short sleep that can be related to the weight gain.”

The arrival of GLP-1 medications has helped women with obesity lose weight at every stage of life, but they should not be viewed as a quick solution, Apovian said.

“If you use a GLP-1 to help your patients lose weight, they need to know this is an indefinite treatment,” she said. “If they lose weight on the drug and you stop the drug, the weight comes back, just like a blood pressure medication.”

Sources/Disclosures

Source:

Apovian CM. Weight management in women across the lifespan. Presented at: Cardiometabolic Health Congress Women’s Cardiometabolic Health and Wellness Masterclass.

Disclosures: Apovian reports participating on advisory boards for Aardvark Therapeutics, AbbVie, Altimmune, Arrowhead Pharmaceuticals, BioAge, Biolinq, Caribou Biosciences, CinFina Pharma, Covidien, Cowen and Co., Currax Pharmaceuticals, Eli Lilly, Form Health, Fractyl Health, Keros Therapeutics, L-Nutra, Mediflix, Metsera Neurocrine Biosciences, NodThera Limited, Nutrisystem, OptumRx, PainScript, Palatin Technologies, Redesign Health, ReShape Lifesciences, Roman Health Ventures, Scholar Rock, Terns, Verily Life Sciences, Veru, Vida Health, Viking Therapeutics, Wave Life Sciences, Wondr Health, Xeno Biosciences and Zyversa Therapeutics; and receiving research funding from GI Dynamics and PCORI.