Estrogen production increases with adiposity in postmenopausal women

Last Updated: 2017-10-17

By Will Boggs MD

NEW YORK (Reuters Health) - Estrogen production increases along with increases in fat tissues in postmenopausal women, researchers from Finland report.

"Adipose tissue is an important peripheral producer of active estrogens after menopause, and the accumulation of visceral fat increases in postmenopausal women," Dr. Natalia Hetemaki from University of Helsinki and Helsinki University Hospital, in Finland, told Reuters Health by email. "Our study sheds light on the physiological production and metabolism of estrogens in two different types of adipose tissue, and our results highlight the role of visceral fat in this respect."

Dr. Hetemaki and colleagues compared estrogen concentrations and metabolic pathways producing estrone and estradiol in subcutaneous and visceral adipose tissue samples obtained from 37 postmenopausal women undergoing laparoscopic or abdominal surgery for nonmalignant indications.

The findings were published online September 29 in The Journal of Clinical Endocrinology and Metabolism.

Estrone, the predominant estrogen in adipose tissue, was present at higher concentrations in visceral than in subcutaneous fat, whereas estradiol concentration was similar in the two compartments.

Estrone concentrations were 8 times higher in subcutaneous adipose tissue and 11 times higher in visceral adipose tissue, compared with circulating estrogen levels, and estradiol concentrations were about 3 times higher in adipose tissue than in serum.

Estrone concentrations in visceral adipose tissue correlated positively with body mass index (BMI), whereas subcutaneous adipose tissue concentrations of estrone correlated negatively with age.

The activity of steroid sulfatase, which hydrolyzes estrone sulfate to estrone, was similar in subcutaneous and visceral adipose tissue, while 17beta-hydroxysteroid dehydrogenases (HSDs), which transform estrone into estradiol, were more active in subcutaneous than in visceral adipose tissue.

In visceral adipose tissue, conversion of estrone to estradiol increased with waist circumference, and estradiol concentrations correlated positively with mRNA expression of HSD17B7.

"Although subcutaneous adipose tissue is quantitatively more important, comprising some 85% of total adipose tissue, increased visceral adipose tissue is associated with risks for diseases such as hormone receptor-positive breast cancer," the researchers note.

"Based on our results, it may be that with increasing obesity, the production of active estrogens is enhanced in visceral more than in subcutaneous fat tissue," Dr. Hetemaki said.

"We will subsequently assess the effect of exogenous estrogens on adipose tissue estrogen metabolism by studying postmenopausal women using systemic postmenopausal hormone therapy," she added.

Dr. Kimberly Cox-York from Colorado State University, in Fort Collins, who recently found age-related differences in subcutaneous adipose tissue estrogen receptor mRNA expression in women, told Reuters Health by email, "This study extends the implications of central adiposity from a matter of lipid handling and chronic inflammatory profiles to direct contributions of adipose tissue to prevailing estrogen profiles. This is of particular concern as we continue to learn more about the associations of lifetime circulating estrogens (estradiol, estrone, and estrogen metabolites) and chronic diseases such as metabolic disease and cancer."

"Quantifying the contribution of visceral and subcutaneous adipose tissue to estrogen metabolism will allow for a more targeted understanding of the risks associated with abdominal adiposity, and the potential to modulate estrogen profiles as women age," she said.

"It is, of course, possible that the prevailing estrogen profile is a feed-forward mechanism for increasing central adiposity, given the observation that adipose tissue distribution shifts from the lower body to the upper body with time since menopause," she said. "This will be a difficult timeline to resolve."

"This work further emphasizes the risk associated with increasing abdominal adiposity," Dr. Cox-York said. "Physicians should continue to encourage pre- and postmenopausal women to maintain a balanced diet and exercise regimen. Estrogen metabolism and action are complex processes, and no single tissue or enzyme directs the outcome. However, we know enough about the major players to guide women toward behaviors that support health."

SOURCE: http://bit.ly/2xN4TWP

J Clin Endocrinol Metab 2017.