Hormone Biomarkers: Dihydrotestosterone (DHT)

Optimal Takeaways

Dihydrotestosterone is a potent androgen. It is primarily synthesized from testosterone and promotes the development of male characteristics. Optimal levels may be protective in men.

Low levels are associated with metabolic dysfunction and cognitive decline. Higher levels of DHT are associated with PCOS, hirsutism, and testosterone therapy.

Standard Range:

Male: 12 - 65 ng/dL (0.41 - 2.24 nmol/L)

Female: 0 - 20 ng/dL (0 - 0.69 nmol/L)

The ODX Range:

Male: 50 - 65 ng/dL (1.72 - 2.24 nmol/L)

Female: 3 - 15 ng/dL (0.10 - 0.52 nmol/L)

Low DHT in men is associated with an increased risk of ischemic heart disease and stroke, insulin resistance, metabolic syndrome, diabetes, and cognitive decline (Swerdloff 2017). Low DHT in women (and men) has been associated with dementia (Swerdloff 2017).

High DHT in men may be seen with testosterone therapy. High DHT in women may be seen in women with PCOS, hirsutism, and acne though elevations may be related to decreased SHBG (Swerdloff 2017).

Overview

Dihydrotestosterone is the most potent of the androgen hormones. It is primarily synthesized from testosterone via 5-alpha reductase in the prostate, liver, and skin. Most circulating DHT is bound to sex hormone-binding globulin. Androgen-sensitive tissues can regulate intracellular DHT by reducing synthesis or increasing metabolism to other compounds, so circulating levels don’t necessarily correlate with tissue levels (Swerdloff 2017). Unlike testosterone, DHT is not metabolized to estrogen.

DHT promotes masculine characteristics and development. It plays a significant role in male physiology, including sexual organ development, prostate growth, sebaceous gland activity, hair growth (body, face, and pubic hair), and even male pattern baldness. Unlike testosterone, DHT is not metabolized to estrogen (Kinter 2023).

Levels may increase with testosterone therapy or decrease with inhibition of 5-αalpha reductase. In men with prostatic hypertrophy, inhibition of 5-alpha reductase will decrease the size and function of the prostate. However, low levels of DHT are associated with insulin resistance, metabolic syndrome, and diabetes, and a full clinical assessment and monitoring should accompany inhibition of DHT synthesis (Swerdloff 2017).

A study of older community-dwelling men (70-89 years old) found that those with a DHT at or above the median of 39 ng/dL (1.34 nmol/L) had a lower risk of ischemic heart disease as well as lower overall mortality (Yeap 2014).

An observational study of 1032 men 66-97 years old found that those with a DHT between 50 and 75 ng/dL (1.74-2.6 nmol/L) had the lowest risk of ischemic stroke while those with a DHT below 50 ng/dL or above 75 ng/dL had the most significant risk (Shores 2014).

The physiological role of DHT in women is less clear than it is in men. In women, circulating levels of DHT are ten times lower than testosterone levels. Using the more sensitive LC-MS/MS method, research observed that healthy premenopausal women maintained a DHT of 9 ng/dL (0.3 nmol/L), and postmenopausal women maintained a level of 3 ng/dL (0.1 nmol/L) (Swerdloff 2017).

In an earlier small study of pre-and postmenopausal hypercortisolemic women with severe depression, DHT trended higher for those with depression with a mean of 18.7 ng/dL (0.656 nmol/L) versus 13.9 ng/dL (0.483 nmol/L) in controls without depression (Weber 2000).

References

Shores, Molly M et al. “Testosterone and dihydrotestosterone and incident ischaemic stroke in men in the Cardiovascular Health Study.” Clinical endocrinology vol. 81,5 (2014): 746-53. doi:10.1111/cen.12452

Swerdloff, Ronald S et al. “Dihydrotestosterone: Biochemistry, Physiology, and Clinical Implications of Elevated Blood Levels.” Endocrine reviews vol. 38,3 (2017): 220-254. doi:10.1210/er.2016-1067

Yeap, Bu B et al. “In older men an optimal plasma testosterone is associated with reduced all-cause mortality and higher dihydrotestosterone with reduced ischemic heart disease mortality, while estradiol levels do not predict mortality.” The Journal of clinical endocrinology and metabolism vol. 99,1 (2014): E9-18. doi:10.1210/jc.2013-3272

Yeap, Bu B. “Testosterone and its metabolites: differential associations with cardiovascular and cerebrovascular events in men.” Asian journal of andrology vol. 20,2 (2018): 109-114. doi:10.4103/aja.aja_50_17

Weber, B et al. “Testosterone, androstenedione and dihydrotestosterone concentrations are elevated in female patients with major depression.” Psychoneuroendocrinology vol. 25,8 (2000): 765-71. doi:10.1016/s0306-4530(00)00023-8