Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Jan;26(1):32-38.
doi: 10.1097/GME.0000000000001162.

A prospective study of inflammatory biomarker levels and risk of early menopause

Elizabeth R Bertone-Johnson  1 , JoAnn E Manson  2   3   4 , Alexandra C Purdue-Smithe  1 , Susan E Hankinson  1   2   3 , Bernard A Rosner  2   5 , Brian W Whitcomb  1
Affiliations

A prospective study of inflammatory biomarker levels and risk of early menopause

Elizabeth R Bertone-Johnson et al. Menopause. 2019 Jan.

Abstract

Objective: Early menopause, the cessation of ovarian function before age 45, has consequences for fertility and cardiovascular health. Evidence from studies of women with autoimmune conditions and genetic studies supports a role for inflammation in early menopause, but the association of inflammatory markers and risk has not been directly evaluated.

Methods: We assessed the relation of the soluble fraction of tumor necrosis factor alpha receptor 2 (sTNFR2), C-reactive protein, interleukin-6 (IL6) levels with incident early menopause among Nurses' Health Study II participants who provided a premenopausal blood sample in 1996 to 1999. Cases (n = 328) were women reporting natural menopause between blood collection and age 45.Controls (n = 492) included (1) 328 women with menopause after age 47, matched 1:1 with cases on age at blood collection and other factors; and (2) 164 additional women with menopause after age 45.

Results: In multivariable models comparing cases and n = 492 controls, we observed a significant association of sTNFR2 levels and risk of early menopause (P = 0.002). Compared with women with the lowest sTNFR2 levels, odds ratios (95% CIs) for quartiles 2 to 4 were 0.60 (0.38-0.95), 0.93 (0.61-1.43), and 1.40 (0.93-2.11). Results further adjusting for antimüllerian hormone levels were similar in magnitude, as were results from sensitivity analyses of matched cases and controls (n = 328 pairs), nonsmokers, and leaner women. C-reactive protein and IL6 levels were unrelated to risk.

Conclusions: The observation of lower risk of early menopause among women with moderate sTNFR2 levels compared with women with lower and higher levels warrants further prospective study.

PubMed Disclaimer

Conflict of interest statement

Financial disclosures/conflicts of interest: None reported.

References

    1. Broekmans FJ, Soules MR, Fauser BC. Ovarian aging: Mechanisms and clinical consequences. Endocr Rev. 2009;30:465–493. - PubMed
    1. Muka T, Oliver-Williams C, Kunutsor S, et al. Association of age at onset of menopause and time since onset of menopause with cardiovascular outcomes, intermediate vascular traits, and all-cause mortality: A systemic review and meta-analysis. JAMA Cardiol. 2016;1:767–76. - PubMed
    1. Shuster LT, Rhodes DJ, Gostout BS, Grossardt BR, Rocca WA. Premature menopause or early menopause: Long-term health consequences. Maturitas. 2010;65:161–166. - PMC - PubMed
    1. Nelson LM. Clinical practice. Primary ovarian insufficiency. N Engl J Med. 2009;360:606–614. - PMC - PubMed
    1. Simpson JL. In: Tarlatzis BC, Bulun SE, editors. Trilogy 8: Premature ovarian failure and perimenopause. Genetics of premature ovarian failure; Proceedings of the International Federation of Fertility Societies 21st World Congress on Fertility and Sterility and the 69th Annual Meeting of the American Society for Reproductive Medicine; Boston, MA. 2013. pp. 123–136.

Publication types