Hormone Biomarkers: FSH, Postmenopausal

Optimal Takeaways

Follicle-stimulating hormone (FSH) is primarily considered a reproductive hormone. However, FSH levels in menopause have been associated with various health issues.

Higher FSH levels have been linked with decreased bone mineral density, increased bone loss, renal dysfunction, higher total and LDL cholesterol levels, and mild cognitive impairment.

Despite these associations, higher FSH levels have been associated with increased insulin sensitivity and decreased risk of metabolic syndrome, prediabetes, and type 2 diabetes. However, the precise mechanisms behind FSH’s impact on energy and metabolic health remain unclear.

Standard Range: Postmenopausal  23.0-116.3  mIU/mL (Immunoassay)

Low FSH in menopause may be associated with an increased risk of metabolic syndrome, insulin resistance, prediabetes, and diabetes (Lee 2022).

High FSH in menopause may be associated with decreased bone mineral density and menopause-related bone loss (Park 2021, Shieh 2019), renal dysfunction (Li 2021), increased total and LDL cholesterol (Song 2016), and mild cognitive impairment (Hestiantoro 2017).

Research also suggests that higher FSH may be associated with decreased risk of metabolic syndrome, insulin resistance, prediabetes, and type 2 diabetes (Lee 2022, Gao 2018, Bertone-Johnson 2017).

Overview

Menopause is associated with the depletion of ovarian reserves, which causes a decrease in circulating estradiol and an increase in follicle-stimulating hormone levels. Research suggests that FSH may have effects beyond reproduction and can affect the liver, bone, and adipose tissue, with physiological changes in hepatic cholesterol synthesis, gluconeogenesis, and osteoarthritis (Li 2021).

Research suggests a higher postmenopausal FSH is associated with decreased fasting plasma glucose, fasting insulin, hemoglobin A1C, prediabetes, and type 2 diabetes. One study of 291 postmenopausal women evaluated the relationship between postmenopausal FSH levels and metabolic syndrome. Results indicated that those with metabolic syndrome had significantly lower median FSH (49.8 vs. 53.9 mIU/mL), estradiol (10.0 pg/mL versus 18.6 mIU/mL), and HDL-C. Those with metabolic syndrome had significantly higher fasting plasma glucose, fasting insulin, HOMA-IR, triglycerides, blood pressure, BMI, waist-to-hip ratio, percent body fat, and visceral fat. When evaluating data by quartiles, those in the lowest quartile (41.23 mIU/mL or below) had a significantly increased risk of metabolic syndrome than those in the highest quartile (63.70 mIU/mL or above). Hormones were measured using a chemiluminescent microparticle immunoassay technique. Researchers note that the mechanism associated with FSH and energy metabolism remains unclear (Lee 2022).

Levels of FHS above 50 mIU/mL were associated with a significantly decreased risk of type 2 diabetes in a prospective population-based cohort study comprising 1,173 postmenopausal women. Researchers found a 1.9% reduced risk of T2DM with each 1-unit increase in FSH (Bertone-Johnson 2017).

Higher FSH may also be associated with serum lipid changes in menopause. A median FSH of 78.3 mIU/L or above was associated with significantly higher total and LDL cholesterol in a study of 400 healthy postmenopausal women despite no significant differences in estradiol. The more elevated FSH and total and LDL cholesterol decreased significantly with hormone replacement therapy, which incorporated estradiol and synthetic progesterone. A decrease in FSH of at least 30% was associated with the most dramatic cholesterol reduction (Song 2016).

Increasing FSH may be associated with changes in renal status as well. Kidney function may decline progressively from pre- to postmenopause, a change associated with decreased glomerular filtration rate and increasing creatinine and serum FSH. One observational cross-sectional study of 2,540 postmenopausal, 121 peri-menopausal, and 624 pre-menopausal women found that increasing FSH was an independent risk factor for kidney dysfunction by the time women reached menopause. The study demonstrated a steady increase in FSH from 8.65 to 56.49 to 71.50 mIU/mL and a steady decrease in estradiol [66.75 to 19.12 to 5.58 pg/mL (245.04 to 70.19 to 20.48 pmol/L)] from pre- to peri- post-menopause, respectively. The estimated glomerular filtration rate significantly decreased, and serum creatinine significantly increased with menopause, i.e., from 108.72 to 88.73 and from 0.65 to 0.73 mg/dL (57.47 to 64.55 umol/L), respectively. Postmenopausal women in the study also had significantly higher luteinizing hormone, uric acid, triglycerides, total cholesterol, LDL-C, fasting plasma glucose, and blood pressure, and lower HDL-C than pre- or peri-menopausal women. Hormones were measured using chemiluminescence techniques (Li 2021).

Loss of bone mineral density in menopause has traditionally been attributed to decreasing estradiol. However, FSH is considered the most significant predictor of bone loss during the transition to menopause, and increased levels are associated with reduced bone mineral density (BMD) and increased bone loss. A cross-sectional study that included 141 healthy women 30-70 years of age found bone mass was lower in all stages of menopause, especially in early postmenopause. Lower BMD in the spine and hip were significantly associated with higher FSH levels independent of estradiol. Earlier research found that serum FSH above 30 mIU/mL was associated with increased bone turnover markers, suggesting rapid bone loss. The current study found the 30 mIU/mL and above threshold was associated with BMD reduction in the spine and hip starting in late perimenopause (Park 2021). Higher FSH levels were associated with elevations in markers of bone resorption, including osteocalcin and CTX, in a cross-sectional study of 92 healthy postmenopausal women. At the same time, no association with estradiol was found (García-Martín 2012).

Data from the Study of Women’s Health Across the Nation (SWAN) suggests that each doubling of FSH was associated with a 39% increased risk for significant bone loss at the lumbar spine and a 27% greater risk of loss at the femoral neck. A halving of estradiol was associated with a 10% loss at the lumbar spine and a 12% loss at the femoral neck. Researchers conclude that measuring FSH is more effective than estradiol in the pre- or peri-menopausal period for identifying women at risk of imminent bone loss within the year (Shieh 2019). However, earlier research on 433 healthy postmenopausal women suggests that the amount of time since menopause had a more substantial impact on postmenopausal osteopenia and osteoporosis than FSH or estradiol (Yoldemir 2012).

Follicle-stimulating hormone may have some effect on cognition during menopause. A cross-sectional study of 282 postmenopausal women found that FSH levels were significantly higher with mild cognitive impairment (MCI), as was the ratio of FSH to estradiol, while differences in estradiol itself were nonsignificant. The mean FSH and FSH:Estradiol ratio was 35.9 mIU/mL and 2.384, respectively, in those with MCI… and 30.91 mIU/mL and 2.088 in those without MCI (Hestiantoro 2017).

References

Bertone-Johnson, Elizabeth R et al. “Association of follicle-stimulating hormone levels and risk of type 2 diabetes in older postmenopausal women.” Menopause (New York, N.Y.) vol. 24,7 (2017): 796-802. doi:10.1097/GME.0000000000000834

Gao, Lihong et al. “Follicle-stimulating hormone associates with metabolic factors in postmenopausal women.” Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology vol. 34,12 (2018): 1035-1038. doi:10.1080/09513590.2018.1482868

García-Martín, Antonia et al. “Role of serum FSH measurement on bone resorption in postmenopausal women.” Endocrine vol. 41,2 (2012): 302-8. doi:10.1007/s12020-011-9541-7

Hestiantoro, A et al. “FSH to estradiol ratio can be used as screening method for mild cognitive impairment in postmenopausal women.” Climacteric : the journal of the International Menopause Society vol. 20,6 (2017): 577-582. doi:10.1080/13697137.2017.1377696

Lee, Suk Woo et al. “Relationship between metabolic syndrome and follicle-stimulating hormone in postmenopausal women.” Medicine vol. 101,18 e29216. 6 May. 2022, doi:10.1097/MD.0000000000029216

Li, Qihang et al. “High Circulating Follicle-Stimulating Hormone Level Is a Potential Risk Factor for Renal Dysfunction in Post-Menopausal Women.” Frontiers in endocrinology vol. 12 627903. 1 Apr. 2021, doi:10.3389/fendo.2021.627903

Park, Young-Min et al. “Bone Mineral Density in Different Menopause Stages is Associated with Follicle Stimulating Hormone Levels in Healthy Women.” International journal of environmental research and public health vol. 18,3 1200. 29 Jan. 2021, doi:10.3390/ijerph18031200

Shieh, Albert et al. “Estradiol and Follicle-Stimulating Hormone as Predictors of Onset of Menopause Transition-Related Bone Loss in Pre- and Perimenopausal Women.” Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research vol. 34,12 (2019): 2246-2253. doi:10.1002/jbmr.3856

Song, Yang et al. “Follicle-Stimulating Hormone Induces Postmenopausal Dyslipidemia Through Inhibiting Hepatic Cholesterol Metabolism.” The Journal of clinical endocrinology and metabolism vol. 101,1 (2016): 254-63. doi:10.1210/jc.2015-2724

Yoldemir, Tevfik et al. “The impact of serum FSH and estradiol on postmenopausal osteoporosis related to time since menopause.” Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology vol. 28,11 (2012): 884-8. doi:10.3109/09513590.2012.683066