Yes, testosterone can be elevated without medication, and this may be contributing to his refractory hypertension.
Men can have naturally elevated testosterone levels ("physiological hyperandrogenism"), and emerging evidence suggests this is directly associated with hypertension, particularly when total testosterone is elevated rather than dihydrotestosterone (DHT).
Understanding Natural Testosterone Elevation
Elevated testosterone without exogenous supplementation does occur in men and represents a distinct clinical entity. Research identifies two types of physiological hyperandrogenism 1:
- Total testosterone elevation - associated with hypertension in 23.5% of cases
- DHT elevation - notably shows NO cases of hypertension
This distinction is critical: if your patient has elevated total testosterone (not DHT), there is a direct pathophysiological link to his blood pressure problems 1.
The Testosterone-Hypertension Connection
The relationship between testosterone and hypertension is sex-specific and concentration-dependent:
In Men with Elevated Testosterone:
- Higher testosterone levels are paradoxically associated with increased hypertension risk in some populations 2, 3
- The hypertension pattern shows characteristic early morning blood pressure rises 1
- Mechanisms involve the renin-angiotensin system activation 2
- Associated with elevated 17-hydroxypregnenolone, 17-hydroxyprogesterone, and androstenedione 1
Critical Caveat - The Age Factor:
Most large studies show an inverse relationship between testosterone and hypertension in aging men 4, 5. Lower testosterone typically correlates with higher hypertension risk in men over 40. However, this represents the more common scenario of age-related testosterone decline, not physiological hyperandrogenism 4, 5.
Clinical Workup for Your Patient
Measure the following to characterize his hyperandrogenism:
- Fasting morning total testosterone (on two separate occasions per standard guidelines 6)
- DHT levels - to distinguish the type of hyperandrogenism 1
- Estradiol - lower levels within normal range correlate with hypertension in testosterone-elevated men 1
- Renin activity - may be elevated with testosterone-associated hypertension 2
- 17-hydroxypregnenolone, 17-hydroxyprogesterone, androstenedione - elevated in testosterone hyperandrogenism 1
Blood Pressure Monitoring Strategy
Given the characteristic pattern, perform 24-hour ambulatory blood pressure monitoring specifically examining early morning hours when testosterone-associated hypertension manifests most prominently 1.
Important Pitfalls to Avoid
Do not assume cardiovascular benefit from high testosterone. While guidelines note that testosterone replacement therapy shows neutral or possibly beneficial cardiovascular effects 7, this applies to therapeutic normalization in hypogonadal men, not physiological hyperandrogenism. The 2023 data specifically demonstrates that naturally elevated total testosterone can drive hypertension 1.
Distinguish from pseudo-resistant hypertension before attributing refractoriness to testosterone. Ensure accurate blood pressure measurement technique, verify medication adherence, and rule out secondary causes like obstructive sleep apnea (which can coexist with hormonal abnormalities) 8, 9.
Management Implications
If confirmed testosterone hyperandrogenism with hypertension:
- Optimize antihypertensive therapy targeting the renin-angiotensin system given the mechanistic involvement 2
- Address metabolic factors as these mediate the testosterone-ASCVD relationship 3
- Monitor for target organ damage given the 23.5% hypertension incidence in this population 1
- Consider endocrinology referral if testosterone remains persistently elevated to rule out androgen-secreting tumors or other pathological causes
The evidence strongly supports that your patient's elevated testosterone could be naturally occurring and directly contributing to his treatment-resistant hypertension through renin-angiotensin system activation and altered steroidogenesis 1, 2.