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Date of release: 30 October, 2017

Can a lower FSH in postmenopausal women predict cardiovascular risk?

Wang and colleagues have carried out a cross-sectional study from a 22-site population-based study known as SPECT-China (the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors) [1]. Among other parameters, the authors measured quartiles of serum FSH in a postmenopausal population (average age 63 years) and related this to a calculated 10-year risk of atherosclerotic cardiovascular disease (ASCVD). The increase in FSH levels was inversely correlated with the ASCVD risk, decreasing from 4.9% to 3.3% for higher FSH levels. These associations seemed to remain after adjustments for obesity, diabetes and other metabolic parameters, although body mass index (BMI) and waist circumference showed the strongest associations. The authors concluded that a low FSH might be a risk factor or biomarker for cardiovascular disease in postmenopausal women.

Comment

FSH begins to increase in the perimenopause and stabilizes at an elevated level about 2 years after the last menstrual period, based on prospective data from SWAN [2]. FSH pulsatility increases during menopause and levels may decrease somewhat in late menopause.

It is known that FSH is negatively associated with obesity, fatty liver and diabetes [3-5], which means that a lower level is found more commonly in these states. Here, the authors have found that lower FSH levels were associated with higher 10-year ASCVD risk. Although a spectrum of FSH values was assessed in the quartile groups, the lower two quartiles had levels which were < 47.47 IU/l and 47.48–61.2 IU/l. In these groups, there was more obesity, more insulin resistance and higher testosterone levels among several parameters which fit the profile of metabolic syndrome and a PCOS-like phenotype. Thus, sex steroids and other factors which can have a direct impact on ASCVD risk also result in negative feedback on the hypothalamic-pituitary axis, and thus are associated with lower FSH levels. In a long-term follow-up of women with PCOS from Sweden, in late menopause, free testosterone was still slightly elevated and FSH levels were found to be lower [6]. Thus, it could be considered that the finding of a lower FSH in these higher-risk postmenopausal women is merely a reflection of a higher risk from a metabolic disorder. Although in this study various adjustments were made, it is not definitive in a cross-sectional study such as this that such adjustment can rule out any interaction. Clearly BMI showed the strongest association in the data set.

Contrary to these findings, however, are the findings of FSH receptors on the liver and adipose tissue, and that FSH has been thought to directly influence hepatic metabolism leading to dyslipidemia [7] and also to be involved with an increase in fat accumulation after menopause [8]. Perhaps a feedback mechanism also exists for adipose tissue possibly to attenuate FSH secretion.

From a practical standpoint, since FSH is pulsatile and wide ranges of values occur after menopause, it may be difficult to ascribe a level which may impart a risk. The authors state that a 'relatively low level of FSH in postmenopausal women might be a risk factor or biomarker for CVD risk'. This is easier said than done, but we await further studies on this matter.

Comentario

Rogerio A. Lobo


Department of Obstetrics & Gynecology, Columbia Presbyterian Medical Center, New York, NY, USA



    References

  1. Wang N, Shao H, Chen Y, et al. Follicle-stimulating hormone, its association with cardiometabolic risk factors, and 10-year risk of cardiovascular disease in postmenopausal women. J Am Heart Assoc 2017;6; pii: e005918


    http://www.ncbi.nlm.nih.gov/pubmed/28855169

  2. Randolph JF Jr, Zheng H, Sowers MR, et al. Change in follicle-stimulating hormone and estradiol levels across the menopausal transition: effect of age at the final menstrual period. J Clin Endocrinol Metab 2011;96:746-54


    http://www.ncbi.nlm.nih.gov/pubmed/21159842

  3. Wang N, Li Q, Han B, et al. Follicle stimulating hormone is associated with non-alcoholic fatty liver disease in Chinese women over 55 years old. J Gastroenterol Hepatol 2016;31:1196-202


    http://www.ncbi.nlm.nih.gov/pubmed/26678239

  4. Wang N, Kuang L, Han B, et al. Follicle stimulating hormone associates with prediabetes and diabetes in postmenopausal women. Acta Diabetol 2016;53:227-36


    http://www.ncbi.nlm.nih.gov/pubmed/25959422

  5. Bertone-Johnson ER, Virtanen JK, Niskanen L, et al. Association of follicle stimulating hormone levels and risk of type 2 diabetes in older postmenopausal women. Menopause 2017;24:796-802


    http://www.ncbi.nlm.nih.gov/pubmed/28141661

  6. Schmidt J, Brannstrom M, Landin-Wilhelmsen K, Dahlgren E. Reproductive hormone levels and anthropometry in postmenopausal women with polycystic ovary syndrome (PCOS): a 21-year follow-up study of women diagnosed with PCOS around 50 years ago and their age-matched controls. J Clin Endocrinol Metab 2011;96:2178-85


    http://www.ncbi.nlm.nih.gov/pubmed/21508129

  7. Song Y, Wang ES, Xing LL, et al. Follicle stimulating hormone induces postmenopausal dyslipidemia through inhibiting hepatic cholesterol metabolism. J Clin Endocrinol Metab 2016;101:254-63


    http://www.ncbi.nlm.nih.gov/pubmed/26583582

  8. Liu XM, Chan HC, Ding GL, et al. FSH regulates fat accumulation and redistribution in aging through the Gαi/Ca (2+)/CREB pathway. Aging Cell 2015;14:409-20


    http://www.ncbi.nlm.nih.gov/pubmed/25754247