Essentials: Tools for Hormone Optimization in Males | Dr. Kyle Gillett
Dr. Kyle Gillett, a dual board-certified physician, joins Dr. Huberman to discuss science-based tools for optimizing male hormones across the lifespan. They cover bloodwork, diet, exercise, stress, purpose, and supplements like creatine, L-carnitine, Tongkat Ali, and Fadogia Agrestis, alongside testosterone therapy and hair loss solutions.
Deep Dive Analysis
16 Topic Outline
Initial Hormone Optimization Steps and Blood Work
Dietary Pillars for Hormone Health
Caloric Restriction and Testosterone Levels
Stress Management and Life Purpose for Hormones
Optimal Exercise Regimen for Hormone Support
Testosterone Replacement Therapy (TRT) in Young Adults
Supplements for Testosterone: Creatine and Betaine
L-Carnitine for Androgen Receptor Density
Vitamin D and Boron for Hormone Optimization
Tongkat Ali and Steroidogenesis
Fadogia Agrestis and LH Release
Testosterone Therapy Dosing and Side Effects
Clomiphene and Selective Estrogen Receptor Modulators (SERMs)
Alcohol's Impact on Testosterone and Aromatase
Tadalafil for Prostate Health and Nocturia
Hair Loss Solutions: Topical Treatments
8 Key Concepts
Sex Hormone Binding Globulin (SHBG)
A protein that binds to androgens and estrogens in the body, regulating the amount of 'free' (bioavailable) hormones. High SHBG can reduce the amount of free testosterone available to act on cells.
IGF-1 (Insulin-like Growth Factor 1)
A hormone that aids in growth, genital development, secondary sexual characteristics, long bone growth, skin, and hair growth. It is particularly important for optimizing growth and bone density up to about age 25.
Prebiotic Fiber
A type of fiber that serves as 'fish food' for beneficial gut microbiome bacteria. Consuming it helps establish and maintain a healthy gut environment, which is important throughout life, especially for brain development.
TMAO (Trimethylamine N-oxide)
A potential carcinogen that can be produced by gut microbiota from the breakdown of L-carnitine and choline. Its production can be influenced by the regulation of one's gut microbiome.
Steroidogenesis Cascade
The biochemical pathway in the body where cholesterol is converted into various sterol hormones, including vitamin D, testosterone, estrogens, and progestogens, through multiple enzymatic steps.
Uricominone
A plant compound found in Tongkat Ali (Longjack) that is considered the main active pharmacological agent. Its standardization in supplements is important for the compound's effects on testosterone synthesis.
Luteinizing Hormone (LH)
A hormone released from the pituitary gland that binds to Leydig cells in the testes. This binding stimulates the Leydig cells to produce and release testosterone.
Nocturia
The medical term for waking up during the night to urinate. Reducing episodes of nocturia can significantly improve sleep quality, which in turn supports growth hormone and testosterone optimization.
14 Questions Answered
Using shared decision-making with a physician, a good follow-up for blood work is usually about every six months to monitor hormone levels like testosterone and SHBG.
Following a pure carnivore or very pure vegan diet in early 20s and certainly teens is a horrible idea as it is likely to significantly decrease free androgens and testosterone.
No, caloric restriction only benefits testosterone if an individual is overweight and has excess body fat; for individuals not carrying excess body fat, it will actually lower testosterone by reducing building blocks for hormones and increasing SHBG.
Vigorous exercise around three to four times a week is sustainable and supportive of hormone status, but training vigorously for longer than an hour, especially regularly, is not hormonally helpful.
Almost never, unless there are rare cases like Kalman syndrome, as it carries significant risks to fertility and other health aspects without clear benefit for those with healthy endogenous production.
Creatine supplementation does not speed up hair loss more than naturally being a male does; it may increase the conversion of testosterone to DHT, but it generally brings an individual to what they are naturally inclined to have, not a supra-physiologic level.
High doses of oral L-carnitine (up to 5 grams/day) can lead to the conversion into TMAO, a potential carcinogen, especially if an individual has a dysregulated gut microbiome.
Tongkat Ali upregulates several enzymes in the steroidogenesis cascade, increasing total and free testosterone, and can also slightly increase DHEA and decrease SHBG, especially if SHBG is very high.
Fadogia Agrestis increases the release of luteinizing hormone (LH) from the pituitary, which then binds to Leydig cells to increase the release of testosterone.
Common side effects can include acne, hair loss, mental status changes (due to testosterone being dopaminergic), cardiovascular concerns, ferritin buildup, fertility issues, and lipid concerns.
Clomiphene has many pharmacodynamic effects beyond blocking estrogen at the hypothalamus and pituitary, including potential visual changes (blurry vision) and effects on various estrogen receptors throughout the body, making it unsuitable for long-term use.
Alcohol significantly increases aromatase, the enzyme that converts testosterone into estrogen, and can decrease testosterone by activating inhibitory neurotransmission, especially with more than 3-4 standard drinks every two weeks.
Yes, low-dose Tadalafil (2.5-5 milligrams per day) can improve prostate health, reduce nocturia (nighttime urination) by half, and increase androgen receptor density, indirectly improving sleep and hormone optimization.
Yes, topical caffeine and topical dutasteride can help with hair loss without significantly affecting systemic DHT levels, unlike topical finasteride which can reduce systemic DHT by about 30%, or topical spironolactone which is systemically absorbed.
21 Actionable Insights
1. Monitor Hormone Levels Regularly
Get blood work done approximately every six months with a physician to monitor hormone progress across the lifespan, including testosterone, SHBG, and free testosterone.
2. Prioritize Diverse Nutrition for Growth
Ensure adequate intake of vitamin D and an array of nutrients, including dairy (for IGF-1), quality animal/non-animal proteins, fruits, vegetables, and starches, especially during development (up to age 25) to support growth and bone density.
3. Emphasize Fiber for Gut Health
Consume prebiotic fiber throughout life, particularly in teenage years, 20s, and 30s, to establish a healthy gut microbiome, which is crucial for brain development and overall health.
4. Tailor Caloric Intake to Body Fat
If overweight, a healthy caloric deficit and exercise can improve testosterone; however, if not carrying excess body fat, caloric restriction will likely lower testosterone by reducing hormone building blocks and increasing SHBG.
5. Manage Stress for Hormone Balance
Actively cope with stress and choose where to direct effort, as chronic stress can negatively impact all other lifestyle pillars, including diet and exercise, thereby disrupting hormone optimization.
6. Define Life Purpose for Self-Actualization
Identify and pursue a life purpose or goal, understanding that goals can evolve over time, as this self-actualization component is crucial for overall well-being and indirectly supports hormone health.
7. Adopt a Sustainable Exercise Regimen
Engage in vigorous exercise around three to four times a week, ensuring sessions last no longer than an hour, and supplement with three to four additional instances of less vigorous exercise for long-term hormonal health.
8. Avoid TRT in Young, Healthy Males
Do not use testosterone replacement therapy (TRT) if you are in your teens, 20s, or 30s with normal testosterone and estrogen levels, as it carries significant risks like fertility suppression and other side effects without clear benefit for those with healthy endogenous production.
9. Consider Betaine for Creatine Non-Responders
If you are a creatine non-responder, consider supplementing with 1-3 grams of betaine to aid amino acid synthesis and energy shunting, especially if homocysteine levels are persistently elevated.
10. Mitigate TMAO from L-Carnitine/Choline
If taking high doses of oral L-carnitine (1-5 grams/day) or choline, consider ingesting allicin (found in garlic) or berberine to help decrease the conversion to TMAO, a potential carcinogen, especially if you have a dysregulated gut microbiome.
11. Optimize Vitamin D for Testosterone
Ensure adequate vitamin D levels, as correcting a deficiency can optimize testosterone production.
12. Use Boron for High SHBG
If you have very high Sex Hormone Binding Globulin (SHBG), consider taking 5-12 milligrams of boron per day to acutely help lower it, which can increase free testosterone.
13. Standardize Tongkat Ali for Efficacy
When using Tongkat Ali (Longjack), pay attention to the standardization for uricominone content, as this plant compound is likely the main active pharmacological effect, influencing its impact on testosterone synthesis.
14. Use Fadogia Agrestis Cautiously
If considering Fadogia Agrestis, use a regimen like 300 milligrams daily or 600 milligrams every other day (or three times a week) to stay within doses that did not show toxicity in rat studies, and monitor for potential pro-inflammatory markers.
15. Monitor Multiple Systems on Testosterone Therapy
If on testosterone therapy, work with a well-versed physician or interdisciplinary team to monitor for side effects across various organ systems, including dermatology (acne, hair loss), mental status (dopaminergic effects), cardiovascular health, ferritin buildup, fertility, and lipid profiles.
16. Avoid Clomiphene for Long-Term Use
Do not use Clomiphene (a SERM) as a long-term strategy for testosterone optimization, as it has many pharmacodynamic effects beyond increasing testosterone, including potential visual changes and impacts on various estrogen receptors throughout the body.
17. Limit Alcohol to Preserve Testosterone
Restrict alcohol intake to no more than three to four standard drinks every two weeks, as alcohol significantly increases aromatase (converting testosterone to estrogen) and can decrease testosterone by activating inhibitory neurotransmission.
18. Consider Low-Dose Tadalafil for Prostate & Sleep
Discuss with your physician the use of low-dose Tadalafil (2.5-5 milligrams per day) for improving prostate health and reducing nocturia (nighttime urination), which can secondarily improve sleep, growth hormone, and testosterone optimization.
19. Use Topical Caffeine for Hair Loss
Apply topical caffeine to the scalp, often in formulations with other weak anti-androgens like ketoconazole, as it can weakly crowd out androgens in the hair follicle and be clinically significant for preventing hair loss.
20. Avoid Topical Spironolactone
Do not use topical spironolactone as a male for hair loss, as its molecule size allows for systemic absorption, potentially leading to unwanted systemic effects.
21. Opt for Topical Dutasteride for Hair Loss
If considering topical DHT blockers for hair loss, topical dutasteride is preferable as it is minimally systemically absorbed and does not affect systemic DHT levels, unlike topical finasteride which can reduce systemic DHT by about 30%.
5 Key Quotes
I don't think development ever ends, but you want to monitor that progress across a person's lifespan.
Kyle Gillett, MD
Hair loss is not a reason to avoid taking creatine.
Kyle Gillett, MD
It's not clear to me that taking one's testosterone from 600 to 800 is always going to be a good thing, especially if estrogen is increasing in parallel.
Andrew Huberman
Tadalafil is a very underrated medication.
Kyle Gillett, MD
Topical dutasteride will not affect your systemic DHT at all.
Kyle Gillett, MD
2 Protocols
Fadogia Agrestis Regimen
Kyle Gillett, MD- Take 300 milligrams a day.
- Alternatively, take 600 milligrams every other day.
- Alternatively, take 600 milligrams three times a week (e.g., Monday, Wednesday, Friday).
Testosterone Therapy Regimen
Kyle Gillett, MD- Administer around 100 to 120 milligrams of testosterone (cypionate or enanthate ester) per week.
- Divide this dose into injections either every other day or three times a week.
- Occasionally, for individuals with higher SHBG, twice a week administration may be sufficient.