Research Blog

August 17, 2022

Hormone Biomarkers: Total Testosterone in Women

Optimal Takeaways

Although testosterone is a major sex hormone in men, it has important effects in women as well. At physiological levels, testosterone helps protect against cardiometabolic disease and supports cognitive health. 

Low levels may be associated with ovarian or adrenal insufficiency, menopause, pelvic radiation, loss of libido, decreased cognitive function, and use of certain medications, including thyroxine and oral contraceptives. High levels of testosterone in women may be associated with masculinization, amenorrhea, polycystic ovaries, excess body hair, smoking, oxidative stress, and increased risk of type 2 diabetes, atrial fibrillation, and stroke.

Conventional Lab Range: Female 2 - 45 ng/dL (0.07 - 1.56 nmol/L)

Optimal Dx’s Optimal Range: Female 35 - 45 ng/dL (1.21 - 1.56 nmol/L)

Low total testosterone in women may be associated with menopause, loss of libido (Bain 2007), atherosclerosis, ovarian insufficiency, adrenal insufficiency, pelvic radiation, and treatment with glucocorticoids, oral contraceptives, thyroxine, phenytoin, phenobarbital, and carbamazepine (Davis 2015). Lower testosterone is associated with hysterectomy and oophorectomy (Sowers 2001), lower baseline memory, and decreased cognitive function in both women and men (Hogervorst 2010).

High total testosterone in women is associated with PCOS, amenorrhea, masculinization, hirsutism (excessive body hair), congenital adrenocortical hyperplasia, and adrenal, ovarian, and trophoblastic tumors (Pagana 2021), smoking, increased weight including fat and lean body mass (Sowers 2001), High serum testosterone was associated increasing advanced glycosylation end products, oxidative stress (Diamanti-Kandarakis 2010), and increased risk of type 2 diabetes (O’Reilly 2019), atrial fibrillation, and ischemic stroke (Zeller 2018).

Overview

Testosterone is an important anabolic steroid hormone in women as well as in men. Approximately 50% of testosterone in women is produced in peripheral adipose tissue from DHEA, 30% from DHEA in the adrenal glands, and 20% is produced in the ovaries (Pagana 2021). Serum levels of testosterone in women are approximately 15-25 times lower than in men (Shea 2014). Total testosterone levels can decrease with age in women, with an observed decline from 37.5 ng/dL (1.3 nmol/L) in a healthy 21-year-old to 18 ng/dL (0.61 nmol/L), presumably due to an expected age-related decline in levels of the testosterone precursor DHEA (Zumoff 1995).

If SHBG is either low (e.g., in obesity or PCOS) or high (e.g., in estrogen therapy or pregnancy), free or bioavailable testosterone should be measured for further clinical assessment (Shea 2014).

Observational studies suggest that low levels of total, free, and bioavailable testosterone increase risk of atherosclerosis, adverse cardiovascular events, and total mortality in women (Davis 2015). Though low levels of testosterone are detrimental in women, increasing levels are also unfavorable and may contribute to atrial fibrillation and ischemic stroke (Zeller 2018).

Higher levels of total testosterone in postmenopausal women were associated with advanced glycation end products (AGEs), a marker of oxidative stress and atherosclerosis risk. Significantly higher AGEs were observed with the highest quartile of testosterone at 53-160 ng/dL (1.8-5.5 nmol/L) versus the lower three quartiles ranging from 20-53 ng/dL (0.7-1.8 nmol/L) (Diamanti-Kandarakis 2010).

A retrospective study comprising 81,889 women revealed that risk of type 2 diabetes increased as testosterone increased above 43 ng/dL (1.5 nmol/L) and risk was highest when testosterone rose to 100 ng/dL (3.5 nmol/L) or above (O’Reilly 2019).

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References

Bain, Jerald. “The many faces of testosterone.” Clinical interventions in aging vol. 2,4 (2007): 567-76. doi:10.2147/cia.s1417

Bentley, Conor et al. “Dehydroepiandrosterone: a potential therapeutic agent in the treatment and rehabilitation of the traumatically injured patient.” Burns & trauma vol. 7 26. 2 Aug. 2019, doi:10.1186/s41038-019-0158-z

Davis, Susan R., and Sarah Wahlin-Jacobsen. "Testosterone in women—the clinical significance." The Lancet Diabetes & Endocrinology 3.12 (2015): 980-992.

Diamanti-Kandarakis, Evanthia et al. “Androgens associated with advanced glycation (end-products in postmenopausal women.” Menopause (New York, N.Y.) vol. 17,6 (2010): 1182-7. doi:10.1097/gme.0b013e3181e170af

Hogervorst, Eef et al. “Are optimal levels of testosterone associated with better cognitive function in healthy older women and men?.” Biochimica et biophysica acta vol. 1800,10 (2010): 1145-52. doi:10.1016/j.bbagen.2009.12.009

Li, Yuanyuan et al. “A dose-response and meta-analysis of dehydroepiandrosterone (DHEA) supplementation on testosterone levels: perinatal prediction of randomized clinical trials.” Experimental gerontology vol. 141 (2020): 111110. doi:10.1016/j.exger.2020.111110

O'Reilly, Michael W et al. “Serum testosterone, sex hormone-binding globulin and sex-specific risk of incident type 2 diabetes in a retrospective primary care cohort.” Clinical endocrinology vol. 90,1 (2019): 145-154. doi:10.1111/cen.13862

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Shea, Jennifer L et al. “Free testosterone: clinical utility and important analytical aspects of measurement.” Advances in clinical chemistry vol. 63 (2014): 59-84. doi:10.1016/b978-0-12-800094-6.00002-9

Sowers, M F et al. “Testosterone concentrations in women aged 25-50 years: associations with lifestyle, body composition, and ovarian status.” American journal of epidemiology vol. 153,3 (2001): 256-64. doi:10.1093/aje/153.3.256

Zeller, Tanja et al. “Low testosterone levels are predictive for incident atrial fibrillation and ischaemic stroke in men, but protective in women - results from the FINRISK study.” European journal of preventive cardiology vol. 25,11 (2018): 1133-1139. doi:10.1177/2047487318778346

Zumoff, B et al. “Twenty-four-hour mean plasma testosterone concentration declines with age in normal premenopausal women.” The Journal of clinical endocrinology and metabolism vol. 80,4 (1995): 1429-30. doi:10.1210/jcem.80.4.7714119

Tag(s): Biomarkers

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