The Shocking Link Between Erectile Dysfunction and Heart Attacks with Dr. Mo Khera

Khera's sexual medicine bloodwork panel extends beyond the standard testosterone/estradiol/PSA screen to include ApoB (preferred over LDL-C), Lp(a) (non-modifiable, but important to know), HbA1c, glucose, and insulin. The goal is to fully characterize cardiometabolic risk at the same visit — because the ED presentation is the opportunity to catch cardiovascular disease before a myocardial infarction or stroke.

Khera's pattern from 17 years of practice: most male patients (especially executives) are decent at diet and exercise but 'lousy' on sleep and stress. Women require stress reduction before they can engage — for women, stress reduction enables sex, whereas for men, sex reduces stress. This means couples therapy and partner education are often needed in parallel with individual treatment. Khera's rule: never raise one partner's libido without the other, or you set up the relationship for conflict.

SubQ testosterone also avoids the transference risk of gels (important in households with pregnant women, infants, or small children). The C vs. E selection mnemonic: C for child (younger), E for elderly. Khera checks hematocrit, estradiol, DHT, testosterone (total and free), SHBG, and PSA at each follow-up visit. He never discusses lab results before asking how the patient feels.

Khera reports that women benefit from testosterone therapy as much as or more than men, particularly for libido. He uses the same symptom-first approach for women: ask how she feels before revealing lab values, and aim for upper-quartile of normal free T. The WHI showed estrogen reduces joint pain; combining testosterone with estrogen adds further benefit for bone density, cognition, and skin.

Khera was the only physician in the US with an FDA IND to study flibanserin (Addyi) in men. The trial showed efficacy. Secondary benefits of Addyi sometimes reported by women: weight loss, improved sleep. Khera's frame: 'you have to work at it too. You have to give me the four pillars.'

Dr. Khera's clinical protocol: when a relatively young man presents with ED and no obvious psychogenic cause, the question becomes whether this is occult cardiovascular disease. Two risk factors (hypertension, diabetes, dyslipidemia, smoking, family history) triggers an immediate cardiology referral. This framing has practical importance because most of these men will present to a urologist or primary care physician, not a cardiologist — so the urologist is the one who must catch the signal. Khera also tracks ApoB (preferred over LDL-C), Lp(a), and HbA1c as part of every sexual medicine workup, precisely because ED should prompt a full cardiovascular metabolic evaluation, not just a PDE5 inhibitor prescription.

The trial did find three small adverse signals worth noting: a slight increase in atrial fibrillation, a slight increase in pulmonary embolism (0.5% to 0.9%), and some increase in acute kidney injury. These small numerical increases exist but must be weighed against the zero signal on the primary endpoint (cardiovascular events) in a specifically high-risk population. Khera emphasizes that in this trial, being above testosterone 350 was considered 'normal' — meaning some men may not have been optimized, which may have diluted any metabolic benefit on the insulin resistance endpoint. The T4DM trial (using nebido at higher testosterone targets) did show improvements in insulin resistance, suggesting the Traverse null result on diabetes may reflect insufficient testosterone dosing rather than a true no-effect.

The estradiol sweet-spot principle has several clinical downstream effects: (1) anastrozole dose should be 0.5 mg once per week, not 1 mg three times per week — the latter causes estrogen-deficient hypogonadism superimposed on testosterone replacement; (2) men also need estrogen for bone mineral density — chronic estrogen suppression causes osteopenia/osteoporosis; (3) the Clomid discrepancy effect is estrogen-mediated: Clomid blocks estrogen receptors in the brain, so ~40% of men on Clomid have elevated testosterone numbers but zero libido improvement — the same men who will feel dramatically better when switched to injectable TRT. The clinical lesson: measure estradiol routinely in all men on TRT and keep it in the 30–50 range, not suppressed.

Clinical implication: for any woman presenting with sexual dysfunction who has a history of long-term OCP use, free testosterone must be measured — not total testosterone. If SHBG is elevated and free T is low, the therapeutic path is to raise total testosterone high enough to overcome the elevated binding capacity. This is mathematically straightforward but requires working above the 'normal' total testosterone range to achieve normal free T — which makes providers uncomfortable without this framing. Khera's analogy: 'the way to win is to increase the total T to overcome and have a higher free T, but you have to be able to follow that free T in women, not the total T.'

Khera's position is absolute: he will not prescribe finasteride or dutasteride to any patient. Alternatives for DHT-related hair loss include oral and topical minoxidil (1.25–2.5 mg oral, with initial shedding expected then recovery), hair transplant, and accepting the loss. For women specifically: the same androgens (testosterone) that can cause hair thinning at excess levels are also the primary driver of libido — so the workaround strategy (don't block androgens, manage topically) is important for women on testosterone therapy who have hair concerns.

Khera's preferred dosing for Clomid: 50 mg every other day (not daily, because 7% of patients develop tachyphylaxis on daily dosing, dropping to near-zero risk with alternate-day dosing). Enclomiphene (the trans-isomer of clomiphene) has a shorter half-life and potentially fewer side effects including less estrogen-blocking in the brain, but remains off-label and requires compounding. For men above LH/FSH of 7.6 — indicating failing testes — neither Clomid nor HCG is likely to work. The right switch point depends on LH/FSH levels: below 7.6, HCG or Clomid can stimulate testicular production; above 7.6, anastrozole (low-dose) or direct testosterone replacement is needed.

Practical corollary: when a patient on TRT has good numbers (500–700) but persistent hypogonadal symptoms, check CAG repeats before concluding that testosterone is not the issue. If CAG repeats are 27+, the clinical correct response is to raise testosterone further within the physiologic range — not to search for a different etiology. The upper-quartile principle (push to the 700–800+ range when symptomatic) applies to both men and women, because everyone has their own symptom threshold. Khera never tells patients their lab values first; he asks how they feel, because knowing the number can create nocebo effects.

Khera's message: 'maybe you're not having sex today, maybe you're not, but maybe you will want to have sex in 5 years and if you don't keep the penile tissue healthy today you won't be able to have sex in 5 years.' The practical options for maintaining tissue health without an active sexual partner include PDE5 inhibitors (Viagra/Cialis at low doses as vascular agents, not just on-demand erection pills), vacuum erection devices, and for patients already on testosterone, the testosterone itself helps maintain corpora cavernosa tissue. Shockwave therapy (class 3 electromagnetic or electrohydraulic devices only) can reverse mild-to-moderate ED by inducing neoangiogenesis, but is ineffective once fibrosis is established.