Dr. Kyle Gillett on Optimizing Hormones: Testosterone, Estrogen, DHT, Prolactin, Supplements and TRT

High-Level Overview

Andrew Huberman talks with Dr. Kyle Gillett, a physician dual board certified in family medicine and obesity medicine who specializes in hormone health for men and women. Over a long, dense conversation, they move from the foundations Gillett calls the six pillars of hormone health (diet, exercise, stress, sleep, sunlight and spirit) to the detailed biology of testosterone, estrogen, DHT, progesterone, growth hormone and prolactin. Along the way they cover hair loss, PCOS, oral contraceptives, alcohol and marijuana, prostate health, testosterone replacement therapy, popular supplements like tongkat ali, fadogia agrestis and boron, hCG, L-carnitine, peptides, relationships, and even caffeine.

The tone is technical but conversational. Huberman often shares his own experiments and blood work, and both repeatedly stress individual variation, regular blood tests, and working with a physician. The conversation starts with broad lifestyle principles and then goes hormone by hormone into mechanisms, specific numbers and practical options.

The Discussion Explores:

• The six pillars of hormone health and why small, consistent lifestyle changes beat bursts of effort
• How caloric restriction, intermittent fasting and sleep affect testosterone and growth hormone
• Testosterone and DHT in women and men, hair loss, and what curcumin and creatine do to DHT
• PCOS, inositol, and how oral contraceptives change hormones, attraction and fertility
• Alcohol, marijuana, sleep supplements, prostate health, pelvic floor and low-dose tadalafil
• TRT dosing, estrogen control, and supplements such as tongkat ali, fadogia, boron and hCG
• Prolactin, dopamine, L-carnitine, peptides and their risks
• How relationships and the spiritual side of health interact with hormones

Deep Dive into Main Ideas

Getting Started: The Six Pillars and Blood Work

Gillett describes his approach as balanced care for body, mind and soul, shaped by medical training at the University of Kansas that emphasized exercise and food as medicine. When a patient has no specific complaint, he looks closely at social and family history and asks how they feel now compared with when they were 20. For people who want their doctor to order hormone tests, he suggests describing concrete symptoms: energy, focus or athletic performance that isn't what it used to be. He notes that women often have more objective data from their menstrual cycles, while men want to know their testosterone but are reluctant to talk about libido or energy.

His foundation is six pillars. Diet and exercise are the strongest, with resistance training especially helpful for hormones and caloric restriction helpful given widespread metabolic syndrome. Then come stress (including family and social health; he notes that changing habits as a household works far better), sleep, sunlight (which includes being outdoors, movement, and cold and heat exposure), and spirit. "The law of diminishing returns applies", he says, so doing a little consistently over a long time beats doing a lot and then nothing. Diet should be individualized, like choosing fuel for different vehicles, and can be guided by biofeedback or genetic testing. He recommends blood tests every three to six months for prevention, both fasting and non-fasting, because "if you're looking for damage to the beach, you don't just look at low tide." Huberman adds his own baseline recommendation of 150 to 180 minutes of zone 2 cardio per week plus resistance training, which Gillett endorses.

Caloric Restriction, Fasting, Growth Hormone and Sleep

Gillett affirms that calories in, calories out holds, and says nothing about fasting is magic for weight loss; about 33% of weight lost is lean mass. The reason to exercise and restrict calories is health span. On testosterone, the evidence depends on your starting point: citing a Mayo Clinic Proceedings systematic review, he says caloric restriction improves testosterone in people with obesity or metabolic syndrome, but a study in young, healthy men found it lowered testosterone. For lean people eating at maintenance, intermittent fasting shouldn't hurt hormones. It may help growth hormone, which gets a large natural spike overnight that is enhanced by fasting, though eating two or three hours before bed still allows good output. He's not worried about natural growth hormone increases from fasting or saunas causing cancer, and explains that IGF-1 lasts days in the blood while growth hormone lasts hours.

Three hormonal issues can hurt sleep: true growth hormone deficiency; the drop in progesterone and its calming metabolites during menopause (and similar changes in men), since those metabolites act on GABA, the brain's main inhibitory system; and, surprisingly, starting testosterone replacement therapy. TRT raises the risk of sleep apnea in a dose-dependent way, even in men who started with normal levels, and can create an overactive, fight-or-flight state in the first months. Huberman cites Robert Sapolsky's view that testosterone amplifies existing traits: "the jerks become bigger jerks."

Testosterone and DHT in Women and Men

Women, Gillett explains, actually have more total testosterone than estradiol (the numbers look different only because they're measured in different units) and even more DHEA. Most comes from theca cells in the ovaries. He mentions female Olympic athletes from Botswana, with XX chromosomes and no hormone use, who naturally produced very high testosterone and were barred from certain distances. For health optimization in women, testosterone is as important to know as estrogen and progesterone, while the latter matter more for preventing breast cancer and osteoporosis.

DHT, a potent androgen, acts on the same single androgen receptor as testosterone. "It helps effort feel good," Gillett says, affecting motivation and even heart tissue. The androgen receptor gene sits on the X chromosome, so men inherit it from their mothers, which is why a maternal grandfather's hairline is a reasonable guess about male pattern baldness. Receptor sensitivity varies with the number of CAG repeats in the gene; fewer repeats mean a more sensitive receptor and more likely hair loss.

Many plant compounds inhibit 5-alpha reductase, the enzyme that converts testosterone to DHT. Curcumin (turmeric) and black pepper extract are examples. Huberman describes feeling a sudden "flatline in energy and vitality after starting a turmeric supplement, which reversed within three or four days of stopping. Gillett says such effects are nearly always reversible, while acknowledging that post-finasteride syndrome is real. People with already low DHT may want to avoid bioavailable curcumin and might be good candidates for creatine, which can increase conversion of testosterone to DHT. Huberman takes five grams of creatine monohydrate a day. For those worried about hair, Gillett says creatine can add fuel to the fire" if someone is already prone to androgen-driven hair loss, but hair lost from follicles that are still alive generally comes back; the shedding people see when starting DHT blockers is often weak hairs being replaced by healthier ones. For male pattern baldness in men or women, he calls dutasteride mesotherapy, localized scalp injections that avoid effects on the prostate and elsewhere, the most promising option.

PCOS, Inositol and Oral Contraceptives

Polycystic ovary syndrome is underdiagnosed, with estimates of 10% to 20% prevalence, and most women learn they have it in their 30s, often when facing infertility. Using the Rotterdam criteria, signs include androgen excess (hormonal acne, chin hair, a deepening voice, male-pattern hair loss), insulin resistance, and infrequent periods, meaning cycles longer than 35 days or fewer than nine a year. Infertility is defined as trying for over a year under age 35, or six months over 35. Treatments include improving body composition, metformin in some cases, and inositol. Gillett distinguishes myo-inositol, an insulin sensitizer, from D-chiro-inositol, a weak anti-androgen, which made Huberman realize the form he had just tried for sleep was myo-inositol. DIM is another option; spironolactone is an anti-androgen that is also a blood pressure medication.

On oral contraceptives, Huberman describes studies showing they flatten women's cycle-driven swings in how attractive they find men, and flatten men's perception of a peak in women's attractiveness around ovulation. Gillett explains that synthetic ethinyl estradiol is about 100 times more potent than natural estradiol in the liver and sharply raises sex hormone binding globulin (SHBG), which lowers free testosterone and DHT and flattens the small testosterone rise at ovulation, along with the libido boost it brings. Choice of progestin affects blood clot risk. After stopping, he says fertility is very likely back to normal within six to twelve months, though SHBG can stay elevated for a while.

Alcohol, Marijuana and Sleep Supplements

Cannabinoids themselves don't lower testosterone, Gillett says, but smoked marijuana likely increases aromatase, converting testosterone to estrogen and suppressing the pituitary signals (LH and FSH) that drive testosterone. Heavy alcohol, like any strong GABA-acting drug, lowers testosterone. He notes the American Heart Association recommends low alcohol intake for men, with red wine's polyphenols possibly protective, while Huberman mentions studies linking even low intake to reduced brain volume. Gillett says daily drinking is mildly immunosuppressive, so two drinks on one day and two on another is better than one every day. The same logic applies to sleep aids: GABA supplements and trazodone shouldn't be nightly, while magnesium and apigenin are fine to take every night.

Prostate Health and the Pelvic Floor

Gillett states that testosterone does not cause prostate cancer, but it will grow an existing cancer, and prostate cancer is extremely common with age: at least a 50% chance on autopsy at 80, and 90% at 90 to 100. So TRT decisions need individual assessment and PSA monitoring. Age matters in interpreting PSA: a 3.9 in a 25-year-old is more concerning than 5.9 in a 75-year-old, because the prostate accumulates damage over time from testosterone, estrogen and growth hormone, and obesity raises risk. For younger men, a key threat is prostate infection, often from gut bacteria since the prostate sits by the colon, so fiber, probiotics and regular bowel movements matter. Men with strong family risk might consider saw palmetto or curcumin. He also mentions hypotheses linking estrogen to prostate cancer, and says a high C-reactive protein, a general inflammation marker, is associated with more reactive oxygen species damaging the prostate.

He describes the pelvic floor as the bottom of a box formed by the abs, back muscles and diaphragm, and notes the growing use of pelvic floor physical therapists. Low-dose tadalafil (Cialis), around 2 to 2.5 milligrams, is increasingly used not for erectile dysfunction but for prostate congestion; he says it can cut nighttime urination, for example from twice a night to once. It can lower blood pressure, raising the risk of fainting during heavy lifts, and he notes that Viagra can affect color vision, so pilots are advised to avoid it.

TRT, Estrogen Control and Testosterone Supplements

For men who truly need TRT, Gillett wants a steady state, avoiding peaks that thicken the blood and crashes that feel bad. Options include injectable esters like cypionate and enanthate, topical testosterone and an oral capsule (Jatenzo) absorbed through the lymph. A typical replacement dose, he says, is about 100 to 120 milligrams per week in total, split into two or three injections. Very few people truly need aromatase inhibitors; crashing estrogen can hurt joints, connective tissue and libido. He says calcium D-glucarate at 500 to 1,000 milligrams can help modestly with estrogen, while DIM lowers both estrogen and androgens. Alcohol, high-fat meals and hCG increase aromatase. People eating little saturated fat aren't at real risk in developed countries, though vegans may need to watch their fat intake, and he describes naturally occurring trans fats from ruminant meat, milk and butter as healthy.

On supplements, turkesterone and ecdysterone act on the beta estrogen receptor and may suit people with low estrogen, possibly with some water retention. Tongkat ali (Indonesian longjack) has placebo-controlled studies, may lower SHBG in some, and weakly inhibits aromatase. Huberman takes 400 milligrams a day and finds higher doses overstimulating. Gillett suggests it may also help women with hyperestrogenism, such as endometriosis, or women coming off birth control, and proposes cycling it 11 months on, one month off. Fadogia agrestis likely increases luteinizing hormone (LH) and LH sensitivity, and he considers it best for people with somewhat low LH and normal estrogen and prolactin. Because long-term evidence is thin, he recommends three weeks on, one week off when combined with tongkat. He discloses that he helped design a testosterone supplement containing both. Huberman took 600 milligrams of fadogia for a long time without problems on blood work. Boron, abundant in Mediterranean soils, can acutely lower SHBG; Gillett cites 3 to 6 milligrams once or twice daily.

hCG closely resembles thyroid-stimulating hormone, and Gillett calls hCG and selenium perhaps the two best things for thyroid health; Huberman gets selenium from three to five Brazil nuts a day. hCG is mainly prescribed for fertility, often 10,000 IU at a time, suppresses LH in a dose-dependent way, can raise estrogen, and is used to help recovery after finasteride. It will also make a pregnancy test positive.

Prolactin, Dopamine and L-Carnitine

Gillett describes a "dopamine wave pool": pushing dopamine too high makes it overflow and crash, and prolactin follows. Estrogen increases prolactin, and prolactin suppresses testosterone. Pituitary microadenomas are extremely common and often go unnoticed; Huberman raises head impacts from contact sports, military service or concussion as possible causes. To lower mildly high prolactin, Gillett suggests first removing casein and gluten, which act on mu-opioid receptors, then considering P5P (the active form of vitamin B6) at 50 milligrams once or twice daily, or vitamin E with mixed tocopherols. He notes a prolactin under about 40 is usually not a big deal, and that P5P doesn't build up the way regular B6 can, which is associated with nerve toxicity.

L-carnitine is a shuttle that moves fatty acids into mitochondria, which especially benefits cells with flagella like sperm, and it slightly increases androgen receptor density. Oral forms are only about 10% bioavailable, so getting one gram means about 10 grams orally, or 15 to 20 capsules; injections are fully bioavailable. It can raise TMAO, and Huberman found that 600 milligrams of garlic (allicin) lowered his TMAO dramatically. Both agree annual blood work across the decades would ideally be standard.

Relationships, Cold and Heat

New relationships are dominated by dopamine. Gillett says you haven't seen every life stage with a partner until you've lived together and raised a baby, when prolactin rises. Being together 24/7 blunts dopamine, while time apart brings back the excitement of reunion, so couples can build this in and plan ahead for hormonal crises like a new baby. Expecting parents of both sexes see a prolactin rise, a human version of brooding or nesting, and he mentions the idea that it may contribute to the so-called dad bod. Prolactin isn't a villain: it supports breastfeeding and helps infants' lungs mature.

Cold exposure won't fix vitamin D deficiency or metabolic syndrome, but cooling testes that run too warm, such as from a varicocele, which about 20 to 25% of men have, can help. "Temperature is the enemy of testes," which prefer to be five to ten degrees cooler than the body. He tells men with infertility or low sperm counts to avoid saunas, and says hot tubs and jacuzzis are the worst offenders. In women, cold increases beta-adrenergic activity and may slightly reduce the drive to eat, but he knows of no change in estrogen.

Peptides: Promise and Caution

Gillett calls insulin the original peptide: lifesaving, yet deadly at the wrong dose, which is why peptides should be prescribed by doctors. Tesamorelin, a growth hormone releasing hormone analog, is FDA approved for lipodystrophy. Growth hormone releasing peptides carry cancer risk, and most of their benefits, like fat loss and lean mass, can be achieved other ways. BPC-157, a version of a protective compound made in the stomach, increases VEGF to grow blood vessels, which is exactly what the cancer drug Avastin blocks, so people with cancer or high cancer risk should avoid it. It isn't FDA approved, and he prefers short courses rather than automatic six-week protocols. Huberman warns that unregulated sources may contain LPS, a bacterial toxin that causes inflammation, and urges working with a physician and a quality compounding pharmacy; he often says "sometimes the best dose of something to take is zero." Bremelanotide (PT-141) is approved for hypoactive sexual desire disorder in women and can help men, but could theoretically fuel melanoma, so Gillett advocates regular skin checks.

Spirit, and a Final Word on Caffeine

Gillett sees body, mind and soul as a Venn diagram: "you can't have one healthy without the other healthy." A Christian himself, he draws resilience from his faith but never pushes beliefs on patients, and says spirituality can be discussed productively with people of any background, citing Alia Crum's work on beliefs affecting physiology. He observes that people tend to split their care among doctors, clergy and therapists, when all three belong together. Asked the most common listener question, whether caffeine harms hormones, he answers: "Only if it affects your sleep."

Conclusion

Dr. Kyle Gillett's message is that hormone health starts with consistent basics, diet, resistance exercise, stress management, sleep, time outdoors and spiritual health, measured over time with regular blood work, and that everything beyond that should be individualized. Many common choices, from turmeric and creatine to birth control, alcohol, marijuana and hot tubs, have real hormonal effects that differ by person. Supplements like tongkat ali, fadogia, boron and L-carnitine, and therapies like TRT, hCG and peptides, can help the right person but carry trade-offs and should be approached cautiously with a physician. For anyone curious about how testosterone, estrogen, DHT and prolactin shape energy, mood, fertility and relationships, this is a detailed, practical tour.

This is a summary of "How to Optimize Your Hormones for Health & Vitality | Dr. Kyle Gillett" from Huberman Lab, giving you the GIST so you can decide if you want the REST. Listen to the full episode.