DR GILLETT WARNS YOUNG MEN ON TRT RISKS TO FERTILITY AND MANIA

Gillett医生警告年轻男性：TRT存在生育受损及躁狂风险 外源性睾酮疗法会永久取代自然的生物节律，并对基线水平健康的年轻男性的生育能力、心血管健康和心理稳定性构成多系统风险。 本期节目提供了男性荷尔蒙优化的综合指南，首先从定期血液检查、压力管理、均衡饮食和规律运动等生活方式基石谈起。Gillett医生详细解释了肌酸、L-肉碱、东革阿里（Tongkat Ali）和Fadogia agrestis等天然补剂如何在生化层面提高睾酮水平和雄激素受体密度。对话还探讨了外源性睾酮疗法的风险与临床现状、Clomid等SERM药物的滥用，以及应对前列腺健康和脱发的策略性方法。最后，节目强调了通过整体、多系统的医学手段来保持活力和生理平衡。 建议大约每6个月进行一次常规验血，以监测总睾酮、游离睾酮和性激素结合球蛋白（SHBG）等关键激素指标。 (0:20) 极端的饮食限制（如严格纯素或纯肉饮食）极不推荐青少年和年轻男性采用，因为这会大幅减少发育所需的游离雄激素。 (2:17) 通过热量缺口减脂有益于脂肪过多者的睾酮水平，但偏瘦人群进入热量缺口反而会导致睾酮水平下降。 (5:36) 剧烈运动持续超过1小时对激素平衡并无益处，最佳方案是每周进行3到4次剧烈运动，并可辅以适度日常活动。 (7:56) 基线睾酮正常的年轻男性强烈不建议接受外源性睾酮替代疗法（TRT），因其存在生育风险及复杂的多系统健康隐患。 (8:59)

Dual board-certified physician Dr. Kyle Gillett outlines an evidence-based framework for male hormone optimization, prioritizing routine diagnostic monitoring, lifestyle foundations, and targeted non-suppressive compounds over premature clinical interventions. He cautions that aggressive pharmaceutical approaches like exogenous testosterone and selective estrogen receptor modulators carry multi-system risks that generally outweigh benefits in healthy men. Diagnostic Biomarkers and Lifestyle Foundations (0:00) Dr. Gillett advises regular blood testing every six months using shared decision-making with a physician, highlighting total testosterone, free testosterone, and sex hormone-binding globulin (SHBG). SHBG binds circulating androgens and estrogens; high levels reduce bioavailable free testosterone and dihydrotestosterone (DHT). Lifestyle fundamentals establish the baseline for these markers. Gillett warns that restrictive diets such as strict carnivore or vegan regimens are ill-advised for adolescents and young adults because they can lower insulin-like growth factor 1 (IGF-1) and free androgens essential for tissue growth and bone mineral accrual. Furthermore, while controlled caloric deficits improve testosterone in men with excess adipose tissue, caloric restriction in lean individuals elevates SHBG, induces catabolism, and depresses free hormone levels. Physical training and toxin management further dictate endocrine status. Gillett recommends three to four vigorous exercise sessions weekly, cautioning that vigorous workouts exceeding one hour become hormonally counterproductive. On alcohol, Gillett reports a direct, dose-dependent upregulation of aromatase—the enzyme converting testosterone to estrogen—alongside GABAergic suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). He advises capping intake at three to four standard drinks every two weeks to prevent endocrine disruption. Nutraceutical Strategies for Hormones and Receptors (10:32) For individuals seeking natural optimization, several non-suppressive compounds enhance synthesis pathways or tissue sensitivity. Creatine supports mitochondrial ATP synthesis and normalizes 5-alpha reductase activity; Gillett clarifies that it does not induce supra-physiological DHT or accelerate hair loss beyond genetic baselines. For non-responders or individuals with elevated homocysteine, betaine (1 to 3 grams) assists methionine processing. L-carnitine, dosed orally at 1,000 to 5,000 mg daily to overcome its 10% bioavailability, increases cytoplasmic androgen receptor density. Because high oral carnitine doses can be converted by gut bacteria into trimethylamine N-oxide (TMAO)—a compound linked to cardiovascular risk—co-administration with allicin (garlic extract) or berberine helps inhibit this conversion. Direct endocrine modulation can be targeted with micronutrients and botanical extracts. Boron (5 to 12 mg daily) serves as an acute tool to suppress elevated SHBG, freeing circulating testosterone, while vitamin D3 corrects foundational sterol deficiencies. In the steroidogenesis cascade, Tongkat Ali (300 to 1,200 mg daily) upregulates steroid synthesis enzymes, making it particularly useful for preserving hormone output during caloric deficits. To stimulate Leydig cell output, Gillett cites Fadogia agrestis as an LH-releasing agent, recommending protocols like 300 mg daily or 600 mg every other day to remain safely below rodent-observed cellular toxicity thresholds. Clinical Liabilities of TRT and SERMs (7:56) Both Huberman and Dr. Gillett express deep concern regarding the growing trend of young men initiating exogenous Testosterone Replacement Therapy (TRT) despite having normal baseline levels between 300 and 900 ng/dL. Exogenous administration permanently replaces natural circadian pulsatility with a flat steady state, shuts down fertility, and introduces systemic risks including lipid panel degradation, microvascular ischemic disease, ferritin accumulation, severe acne, and potential manic psychological episodes driven by dopaminergic stimulation. When medically necessary, Gillett favors micro-dosing protocols—typically 100 to 120 mg of testosterone cypionate weekly, split into bi-weekly or alternate-day injections—under interdisciplinary monitoring across cardiology and hematology. Gillett delivers an equally strong warning against using clomiphene (Clomid) or other selective estrogen receptor modulators (SERMs) as long-term testosterone boosters. While occasionally used as short-term bridges to stimulate pituitary LH release after severe suppression, SERMs bind erratically across five distinct estrogen receptor classes throughout the body. In ocular tissues, Clomid frequently inhibits essential estrogen receptors, causing visual disturbances and blurry vision that can become persistent. Microvascular Support and Targeted Hair Preservation (31:06) Daily low-dose tadalafil (2.5 to 5 mg) is highlighted as an emerging adjunct for men's preventative health. Beyond mild systemic blood pressure reduction and enhanced genital micro-circulation, tadalafil shares L-carnitine’s ability to increase androgen receptor density. Clinically, Gillett notes that low-dose tadalafil roughly halves nocturia episodes; by preventing frequent nighttime awakenings, it consolidates deep sleep architecture vital for endogenous growth hormone and testosterone secretion. Reversible red-green color discrimination impairment represents its main dose-dependent side effect. To manage male pattern baldness without the systemic vigor and libido side effects of oral 5-alpha reductase inhibitors, localized alternatives can be deployed. While topical spironolactone is strongly discouraged due to rapid systemic absorption, topical caffeine and ketoconazole offer mild, localized competition at scalp androgen receptors. Topical finasteride still triggers an approximate 30% reduction in circulating DHT, whereas topical dutasteride exhibits a rapid localized clearance at low doses, effectively protecting scalp follicles without suppressing systemic DHT levels. Gillett and Huberman emphasize that optimizing male endocrine health relies on sustaining fundamental sleep, nutritional, and training habits rather than pursuing arbitrary laboratory targets. While non-suppressive supplements and localized topicals provide measurable functional improvements, systemic pharmaceutical interventions override natural autoregulation and require specialized, interdisciplinary medical oversight.

双专科认证医师 Dr. Kyle Gillett 与 Andrew Huberman 深入探讨了男性终生荷尔蒙优化的综合策略，强调维持健康的睾酮与自由雄激素水平应以定期的血液监测、生活方式干预和靶向补充剂为基石，并对外源性睾酮替代疗法（TRT）和选择性雌激素受体调节剂（SERM）在年轻健康人群中的滥用提出了明确警告。 血液监测与生活方式基石 (0:00) Dr. Gillett 建议男性建立定期健康评估机制，大约每6个月与医生合作进行一次血液检测，重点关注总睾酮、性激素结合球蛋白（SHBG）以及游离睾酮。在青春期与成年早期，过早剔除乳制品可能抑制胰岛素样生长因子1（IGF-1），阻碍长骨和生殖系统的正常发育；而在二十岁出头采取纯肉或严格纯素等极端饮食，容易大幅削减游离雄激素。关于体脂与热量平衡，超重个体通过适度热量亏缺减少脂肪可改善睾酮水平，但体脂偏低的健康人群处于热量赤字状态则会减少激素合成原料、拉高SHBG并直接降低睾酮水平。 在运动与作息管理上，Gillett 推荐每周进行3至4次高强度锻炼，并警告单次剧烈训练超过1小时在荷尔蒙层面有害无益，过度训练易引发生活方式恶化。此外，酒精摄入会直接且呈剂量依赖性地上调芳香化酶活性，促使活性睾酮加速转化为雌激素，同时通过强烈的GABA能神经抑制作用减弱垂体释放促黄体生成素（LH）与促卵泡激素（FSH），建议饮酒频率严格限制在每两周不超过3至4个标准饮酒单位。 关键补充剂与类固醇生成调控 (10:32) 在非抑制自身轴的天然优化策略中，肌酸是基础补充工具，它能够辅助线粒体能量储备并重新平衡DHT转化，Dr. Gillett 澄清了肌酸导致脱发的谣传，指出其仅将个体调节至遗传基础水平而不会引发超生理雄激素。针对肌酸无应答者，可摄入1至3克甜菜碱协同优化同型半胱氨酸代谢。口服左旋肉碱虽生物利用度仅约10%（日剂量常需1至5克），且在高剂量下存在肠道细菌将其转化为心血管风险物氧化三甲胺（TMAO）的隐患，但它与他达拉非类似，具有增加胞质内雄激素受体密度的罕见作用；使用者可结合大蒜素（如600毫克大蒜提取物）降低TMAO产生。 针对类固醇生成级联通路，微量元素硼（每日5至12毫克）可短期急性抑制SHBG以释放游离睾酮，而纠正维生素D3缺乏也是睾酮合成的先决条件。植物提取物东革阿里（Tongkat Ali，每日300至1200毫克）通过上调类固醇生成酶，在低碳水或减脂等IGF-1受抑时期能有效维持激素产出，并能降低过高的SHBG；*Fadogia agrestis*（临床常以600毫克隔日或每周3次给药）则直接刺激脑下垂体释放LH，促使睾丸间质细胞合成内源睾酮，在换算的人体等效剂量下未观察到细胞毒性。 临床药物干预的多系统风险与界限 (23:56) 针对基线处于正常范围（300至900 ng/dL）却寻求外源性TRT以追求精力与恢复的年轻男性，Gillett 与 Huberman 强调该做法弊大于利。外源性雄激素会彻底抹平人体原有的昼夜脉冲节律，完全抑制自身生育力，并带来严重的痤疮、铁蛋白蓄积、血脂恶化、微血管缺血甚至诱发躁狂症等中枢神经风险；若出于临床指征必须使用，Gillett 主张采用每周100至120毫克、分次隔日注射的微量给药方案以保持稳态，且必须由具备心血管、血液和脂质多学科素养的团队监护。 针对目前部分男性利用克罗米芬（Clomid）等SERM类药物提升睾酮的趋势，Gillett 提出严厉批评。SERM只应作为极低内源水平患者的极短期“启动桥梁”，由于人体存在多种雌激素受体亚型，SERM在不同组织具有混乱的双向效应，长期使用会阻断眼部关键雌激素受体，频繁导致不可逆的视觉模糊。相比之下，每日2.5至5毫克的低剂量他达拉非被证实是极具价值的辅助药物，它不仅改善生殖系统微血管流通、增加雄激素受体密度，还能将夜尿症发生频率减半，通过改善深层睡眠间接促进生长激素和睾酮的自身分泌。 脱发防治与外用抗雄激素选择 (33:59) 针对雄激素性脱发的防治，口服DHT阻断剂（如保法止）虽能抑制头皮DHT受体，但常伴随性欲减退和活力下降等全身副作用。对于遗传倾向较轻的个体，可优先考虑局部外用方案。Dr. Gillett 指出，局部外用咖啡因可在物理层面渗透头皮毛囊并微弱竞争排挤DHT，临床上常与酮康唑配伍使用以实现温和的局部抗雄效果。 对于处方级外用抗雄药物，必须根据分子特性严格区分全身暴露风险：外用螺内酯由于分子量小极易被全身吸收，男士应严格禁止使用；外用非那雄胺同样存在全身吸收，通常会导致血清循环DHT水平下降约30%；而低剂量外用度他雄胺由于在血液中的半衰期极短，几乎不降低全身循环DHT，为男性提供了在保留系统雄激素活性的同时遏制局部脱发的替代选择。 荷尔蒙优化绝非单纯盲目追求更高的血液实验室指标，而应以主观体能、精神状态及长期多器官安全为核心。鉴于外源性睾酮和受体调节剂具有不可逆的生殖与心血管风险，非临床缺陷人群应将重心放在生活方式维系、合理营养与低风险补充剂上，药物干预则须在专业多学科医疗监护下严格限定使用。

[7:56] It is not hormonally helpful to train, especially regularly train, vigorously for longer than an hour. [16:51] Kyle Gillett: No reason to cycle any of those. [17:29] Andrew Huberman: Do people feel like they are going to have more energy as a consequence of doing these things? Are they going to have the more optimized libido? Are they going to have more optimized recovery from exercise? [23:56] Kyle Gillett: If your physician that is managing or prescribing your testosterone therapy or your HRT is not well-versed in these systems, you would want him or her to be part of an interdisciplinary team [28:32] Andrew Huberman: Why would I want to take something that would increase the activity of an estrogen receptor? I just can't find the rationale for that.

[0:00] Welcome to Huberman Lab Essentials, [0:01] [music] where we revisit past episodes [0:04] for the most potent and actionable [0:06] science-based [music] tools for mental [0:08] health, physical health, and [0:09] performance. [0:11] I'm Andrew Huberman, and I'm a professor [0:13] of neurobiology and ophthalmology at [0:15] Stanford School of Medicine. And now, [0:17] for my discussion with Dr. Kyle [0:19] Gillette. Dr. Gillette, great to have [0:21] you back. [0:22] >> Great to be back. Thank you. [0:24] >> I'd like to begin with a question about [0:26] what all males ought to do in order to [0:29] optimize their hormones. What should [0:31] they be doing, what should they avoid [0:32] doing if the goal is to have a long arc [0:35] of healthy hormone optimization [0:37] throughout the lifespan? [0:38] >> There's many things that you should do. [0:41] An analogy that I often make is when [0:43] there's a brand new car that comes off [0:45] the assembly line, you do a full scope [0:47] of diagnostic workup, hook it up to the [0:49] computer, and I think we should do the [0:50] same thing with humans as well. During [0:53] puberty, you know, obviously you're a [0:55] functioning human, but I would say [0:57] there's still development, and I think [0:59] that the human always develops. I don't [1:02] think development ever ends, but you [1:04] want to monitor that progress across a [1:06] person's lifespan. [1:08] >> What do you think are the key things to [1:10] look for in blood work? I mean, [1:12] testosterone is always the topic that [1:14] comes up in the context of male hormone [1:16] optimization, but certainly there are a [1:17] lot of other hormones that are important [1:18] as well. [1:19] >> Mhm. And with testosterone, you want to [1:21] get either testosterone and a SHBG or a [1:23] free testosterone. [1:24] >> Could you define SHBG for our listeners, [1:26] please? [1:27] >> It is sex hormone binding globulin. It [1:29] is the protein that binds up all [1:31] androgens and estrogens in the body. So, [1:34] the stronger the androgen, the stronger [1:36] it binds. During puberty, strong [1:39] androgens, especially DHT, which is the [1:41] strongest bioidentical androgen, [1:44] has a huge role, a prominent role in [1:47] secondary sexual characteristics. [1:50] And if your SHBG is very high, then your [1:52] DHT can run higher because it's not [1:54] metabolized, but there's not quite as [1:57] much free DHT. So, you want to balance [1:59] between um a high enough free DHT and a [2:03] high enough total DHT. So, assuming that [2:05] there's no major intervention, how often [2:08] do you recommend that people get their [2:09] blood work done? Using shared [2:11] decision-making with their physician, [2:14] usually a good follow-up is about 6 [2:16] months. [2:16] >> So, on a daily basis, uh maybe you could [2:18] just take us through the arc of a day [2:20] and um [2:21] and push out some of the protocols that [2:23] you use or the things that you like to [2:24] see your male patients use in order to [2:26] try and optimize their hormone status. [2:29] >> I'll briefly touch on some of the [2:30] lifestyle pillars to start. Diet and [2:32] exercise are the first two. [2:34] Um in puberty, sleep is particularly [2:37] important, of course. [2:38] Um but with diet and exercise, uh [2:41] throughout a [2:43] lifespan, you want to not exclude things [2:47] that are helping you. For example, [2:49] during puberty, if you're consuming [2:51] dairy and then all of a sudden you cut [2:52] out all dairy, dairy can help increase [2:54] IGF-1 and free IGF-1. [2:56] >> And what And just uh again, for our [2:58] audience, maybe you just mention what IG [3:00] what having enough IGF-1 can do for us [3:02] that's beneficial is [3:03] >> It helps you grow. It uh helps with uh [3:06] genital development, secondary sexual [3:08] characteristics, and long bone growth. [3:11] Um skin growth, hair growth, a host of [3:13] things. [3:14] >> So, getting an array of nutrients that [3:16] include dairy, what other sorts of [3:18] nutrients are important during [3:19] development? [3:20] >> You want to have adequate vitamin D. [3:22] Vitamin D helps with testosterone [3:23] production. It helps again with bone [3:26] mineralization [3:27] and stature. Um after an age of about [3:31] 25, and there's not a strict cut-off, [3:34] but up to about age of 25, optimizing [3:36] your growth hormone and IGF-1 helps with [3:39] bone density and bone growth. [3:41] So, uh from the dietary standpoint, you [3:44] want to have enough free estrogen, not [3:46] too much when you're growing, but you [3:48] want to help um [3:50] basically stockpile bone to prevent a [3:53] risk of osteoporosis or thin bones [3:55] fractures when you're older. [3:57] >> I realize that some of this relates to [3:59] ethics and food allergies and things of [4:00] that sort, but would you say that on [4:03] balance that most people would benefit [4:06] from eating a combination of you know, [4:09] quality proteins from animal sources and [4:11] non-animal sources, fruits, vegetables, [4:13] and starches? I mean, what do you think [4:16] for instance about people following a [4:17] pure carnivore or a very [4:20] pure vegan diet in their 20s and 30s? [4:23] >> In their late 20s, it might be a [4:24] reasonable option. In early 20s and [4:27] certainly teens, it is a horrible idea [4:29] because it is likely to significantly [4:31] decrease your free androgens. So, you [4:33] will have less testosterone acting on [4:35] receptors through the body. [4:37] >> Are there any other micronutrients or [4:39] macronutrients that people in their 20s [4:41] and 30s should emphasize? [4:42] >> Fiber is going to be paramount in kind [4:45] of like setting your set point of your [4:47] gut microbiome the rest of your life. [4:49] There is prebiotic fiber, which you can [4:52] think of as fish food for your good gut [4:54] microbiome. Your gut microbiome's kind [4:56] of like an aquarium or a fish tank. Any [4:59] fiber or food that you're putting in [5:00] your gut, it's either going to it's [5:02] going to skew your gut microbiome [5:04] towards something that is more [5:05] beneficial or or more detrimental. [5:08] >> And would you say that the prebiotic [5:10] fiber and the getting essential fatty [5:12] acids, that would be important to do [5:15] throughout the lifespan or just for [5:16] people in their 20s and 30s? [5:18] >> Throughout the lifespan, um particularly [5:20] important in the teenage, 20s, 30s [5:23] because it helps with brain development. [5:25] Um you're certainly more of an expert [5:27] than me when it comes to [5:29] um brain development, but it does [5:31] continue to develop through really [5:33] throughout the lifespan, but certainly [5:34] through the 20s and 30s as well. [5:36] >> In a previous discussion of ours, I [5:37] asked you about um caloric restriction [5:40] and testosterone. And if I recall [5:41] correctly, the idea was that if somebody [5:44] is overweight, they have an excess fat [5:46] adipose tissue, then getting rid of some [5:48] of that adipose tissue by through [5:50] caloric restriction and exercise, [5:51] provided it's done not too fast in a [5:53] healthy way, is going to be beneficial [5:55] for testosterone in the long run. But [5:58] that [5:59] for individuals who are not carrying an [6:01] excess of body fat, caloric restriction [6:02] is actually going to lower testosterone. [6:06] First of all, do I have that correct? [6:08] And second, are there any um addendums [6:10] to that that you'd like to to give us [6:12] now? [6:13] >> That's correct. Um if you look at an [6:16] individual in a caloric deficit, several [6:19] changes will happen. One is that they'll [6:21] have less building blocks for hormones. [6:24] Another is that they will be in a [6:25] catabolic state more often, so that [6:27] balance of anabolism and catabolism will [6:30] be different. They'll likely have less [6:32] signaling from growth hormone and IGF-1, [6:35] and they'll also have the high SHBG that [6:38] we defined earlier as the binding [6:39] protein, so their free androgens and [6:42] free estrogens will go down. [6:44] >> Now, what are some of the other pillars [6:46] of creating a the proper environment for [6:48] hormone optimization? [6:49] >> Uh stress is probably the next one. Um [6:52] during [6:53] uh [6:54] both puberty but also the 20s and 30s, [6:57] individuals are [6:59] figuring out how they want to cope with [7:00] stress and also figuring out what they [7:03] want to choose to put their effort into. [7:06] So if someone is over stressed, then it [7:08] can have uh it can [7:10] put all the other lifestyle pillars and [7:12] then they stop dieting well, um they [7:14] stop exercising, and everything else can [7:17] go askew. [7:18] >> What would the be some of the additional [7:19] things that everybody should do? [7:21] >> Another one is finding what your purpose [7:24] is in life. So I call this spirit, but [7:26] it's really just the self-actualization [7:28] component of Maslow's hierarchy of [7:30] needs, which is basically your physical [7:32] needs, your mental needs, and then your [7:34] purpose in life, what you really like to [7:36] do. [7:36] >> The idea is not to pick the end goal, [7:39] it's to pick a goal, and then once you [7:41] reach that goal to assess and then pick [7:44] another goal and so on. I think [7:46] sometimes when people hear about picking [7:47] a purpose, they're like, "Oh my [7:48] goodness, I have to define it." Sort of [7:49] like naming oneself, that you you you [7:51] actually can change your your your goals [7:54] and purpose over time. I'd like to [7:56] return to the key things that people [7:59] should do, or I should say the key [8:00] things that men should do to optimize [8:02] their hormones. What do you think is a [8:03] healthy, sustainable exercise regimen [8:07] that [8:08] anyone can follow that will also support [8:11] their hormone status? [8:12] >> For really vigorous exercise, around [8:15] three to four times a week is very [8:17] sustainable over a long period of time. [8:20] On top of that, you could add in three [8:21] or four more instances of less vigorous [8:25] exercise. When they study the effect of [8:28] exercise, specifically vigorous [8:29] exercise, um one area that's been [8:32] studied is uh vigorous exercise episodes [8:35] lasting longer than an hour. [8:37] And they usually track it by a rating of [8:40] perceived exertion, which isn't perfect, [8:42] and it's not extremely actionable, but [8:44] it's helpful for clinical science. But [8:45] the takeaway from that is basically do [8:48] not It is not [8:50] hormonally helpful to train, especially [8:54] regularly train, [8:56] uh vigorously for longer than an hour. [8:58] >> These days, [9:00] for better or for worse, I think for [9:02] worse, [9:03] younger guys are asking about and using [9:07] testosterone replacement therapy, [9:09] so-called TRT. Why in the world would [9:13] any male in his teens or 20s, [9:17] or even 30s, whose blood levels of [9:20] testosterone and estrogen are at the [9:22] appropriate levels, meaning within the [9:23] normal reference range, why would they [9:25] use [9:26] take exogenous testosterone, [9:29] given all the negative effects on [9:31] fertility, [9:32] um some of the challenges that it can [9:33] present if the dosages aren't quite [9:35] right, et cetera? [9:36] Why would they that? Certainly, if they [9:39] are not being paid for a particular [9:42] endeavor, like they're not making money. [9:43] If they are playing a sport, chances are [9:45] they're not allowed to do that anyway. [9:46] It's It's on the banned substances list. [9:48] So, to me it just seems like a crazy [9:50] idea. Um [9:52] but then again, I'm of a generation that [9:54] really hasn't thought about doing that [9:56] stuff until people were in their 40s and [9:57] 50s at or even never. [10:00] So, [10:01] is there ever a case for somebody in [10:02] their 20s or 30s to take testosterone [10:05] if their blood levels are within the 300 [10:08] to 900 [10:10] nanograms per deciliter reference range? [10:12] >> You know, everyone has their different [10:13] reason [10:14] uh as far as like when does the benefit [10:17] outweigh the detriment? Not very often [10:20] if you're um in your 20s and certainly [10:23] uh probably almost hardly never. There's [10:25] always, you know, rare cases like [10:26] Kallmann syndrome and whatnot, but um [10:30] almost never if you're very young. [10:32] >> Okay, so for people in their 20s, 30s, [10:34] and beyond, 40s, etc., whose uh [10:37] testosterone and estrogen levels are at [10:39] the appropriate ratios and in the within [10:41] the normal reference range, uh libido, [10:44] energy, recovery, etc. and are feeling, [10:47] you know, at least um workable for for [10:49] their lifestyle, [10:51] for those people, [10:52] what can they do besides get great [10:55] sleep, train but not too hard or too [10:57] often, etc., etc.? What are some of the [10:59] things in the realm of supplementation [11:01] that can help them optimize their [11:03] testosterone and estrogen without [11:06] suppressing their own endogenous [11:08] production of testosterone and estrogen? [11:10] >> Let's mention creatine as the first one. [11:13] Creatine is interesting because it has [11:14] multiple different effects. It helps [11:16] with amino acid synthesis. It also helps [11:18] with oxidative stress. It can also serve [11:21] as the backup fuel tank for your [11:23] mitochondria, so kind of holding backup [11:25] ATP, and it does slightly increase total [11:28] testosterone, and And also increases the [11:31] conversion of testosterone to [11:32] dihydrotestosterone. [11:34] So potentially it's especially useful in [11:38] men in their even their teenage years [11:40] and their 20s. [11:41] >> You mentioned the conversion of [11:42] testosterone to dihydrotestosterone and [11:44] there is mythology out there that [11:46] creatine can increase hair loss. I'm [11:48] guessing because there's at least one [11:49] study showing that creatine can increase [11:51] DHT, dihydrotestosterone and DHT is one [11:55] of the primary hormones that can promote [11:57] male pattern baldness. [11:59] So the question therefore is does [12:02] creatine supplementation [12:05] increase the rate of hair loss? [12:07] >> In each individual [12:09] preventing hair loss is a very poor [12:12] reason to take creatine because it's not [12:14] going to take you to a supra [12:16] physiological level. [12:17] It's not going to [12:19] you know increase your androgens to an [12:22] unnormal level of binding. [12:26] So I feel like [12:27] this if that was a reason to not take [12:30] creatine for hair loss, then that's [12:32] >> sorry, you mean hair loss is not a [12:34] reason to avoid taking creatine? [12:36] >> Correct. Hair loss is not a reason to [12:38] avoid taking creatine. It think of it as [12:41] just [12:42] bringing you to what you are [12:45] naturally inclined to have. If your [12:47] conversion of testosterone to DHT is [12:49] already high, then often creatine does [12:51] not affect this. [12:53] It just kind of resets your balance [12:55] between testosterone being aromatized to [12:58] estrogen or being 5 alpha reduced DHT. [13:02] So it's not going to speed up hair loss [13:03] more than just naturally being male [13:06] does. So in some individuals it will [13:08] have no effect. In some individuals for [13:11] whatever reason they have almost no 5 [13:13] alpha reductase activity, it will return [13:15] them to natural or normal. [13:17] >> So what other supplement based tools can [13:20] people consider? [13:21] >> Another one we can loop in with creatine [13:22] is beta-alanine. Some people are [13:24] non-responders to creatine so you can [13:26] increase that to 10 g or you can use its [13:29] cousin beta ean to help with amino acid [13:32] synthesis and shunting of energy. Along [13:35] with that, I would put L-carnitine. [13:37] >> Beta ean, uh do you recall uh [13:40] what dosage people typically would take [13:43] if they're a creatine non-responder? [13:45] >> 1 to 3 g. In fact, yeah, several [13:48] versions of creatine have beta ean mixed [13:50] in because it helps with the processing [13:53] of methionine and homocysteine. [13:55] >> So, if somebody is already taking [13:56] creatine and likes it and responds to [13:58] it, I'll raise my hand, such as myself, [14:00] would adding beta ean help or is it [14:03] redundant with creatine? [14:05] >> Only if their homocysteine is [14:06] persistently elevated. And homocysteine [14:08] is kind of like an inflammatory marker [14:10] that can build up if you're not [14:12] converting enough of it downstream. [14:14] >> How would I know? [14:15] >> Um just a blood test. [14:16] >> So, L-carnitine, uh what are the ways to [14:19] take L-carnitine? I know that there's an [14:21] oral form, so capsules, and there's [14:22] injectables. The injectables, I think [14:24] you need a prescription. Is that right? [14:26] >> Correct. You need a prescription for the [14:27] injectables or you should really get a [14:29] prescription for the injectables. [14:32] For when you inject it, um [14:34] of course, at the supervision of your [14:36] doctor, it's usually done [14:37] intramuscularly. It's an aqueous [14:39] solution, so it does not have like an [14:41] oil or a carrier oil in it like TR like [14:43] testosterone esters do. [14:45] Um however, if you inject it too [14:48] superficially, it's not going to make a [14:50] rake anything. Often, it just burns if [14:51] you inject it subcutaneously and it does [14:54] not uh disseminate throughout the body [14:56] as well. [14:57] L-carnitine potentially has localized [15:00] effects if you inject it. If you ingest [15:03] it orally, then it has a very low [15:06] bioavailability, maybe only 10%. [15:08] >> So, what are the dosages of L-carnitine [15:10] that one needs to ingest then if they [15:12] want to get a benefit because I thought [15:14] only 10% is being absorbed, uh it's [15:17] probably a lot of L-carnitine. How much [15:19] should people take per day? [15:20] >> Usually, I recommend uh for oral [15:22] L-carnitine between 1,000 mg and up to 4 [15:26] or 5,000 mg. [15:28] >> So, 1 to 4, maybe even 5 g. [15:31] >> Correct. [15:31] >> Okay. [15:32] >> Up to 5 g a day. If you're on that much, [15:35] especially if you have a dysregulated [15:37] gut microbiome, you should be concerned [15:39] with TMAO, which is a potential [15:41] carcinogen that both carnitine and [15:43] choline can convert into. [15:45] And your gut microbiota determine how [15:48] much that happens. [15:49] >> Is it true that I can offset any [15:51] negative effects of alpha-GPC, [15:53] uh choline that is, and L-carnitine um [15:56] that I take by ingesting garlic? Is that [15:59] right? [15:59] >> There's a compound in garlic called [16:01] allicin. I believe it's a l l i c i n. [16:04] It's also part of the scientific name, [16:05] the genus of uh types of garlic. [16:09] And this can help decrease the [16:10] conversion to TMAO. Berberine actually [16:12] slightly decreases the conversion to [16:14] TMAO as well. Um probably through [16:16] alteration of the gut microbiome. And [16:18] then just um optimizing your gut [16:20] microbiome can decrease conversion. So, [16:22] not everyone needs allicin, but it's [16:24] something that you should certainly [16:25] consider if you were on a high dose. [16:28] >> I'm going to continue to take the 600 mg [16:31] of garlic every time I take my [16:33] L-carnitine, but I'm going to skip the [16:35] berberine cuz berberine gives me brutal [16:36] headaches and it makes me crave [16:37] carbohydrates because it drops my blood [16:39] sugar. [16:40] >> It has many other effects, including the [16:41] dawn phenomenon where it drops your [16:43] blood sugar when you're sleeping and you [16:45] can't even realize it. [16:46] >> Okay, and what we did not talk about is [16:48] what L-carnitine does. [16:50] >> It's a shuttle. So, I think it's named [16:52] carnitine palmitoyl coenzyme A. [16:55] Basically, it's it just takes nutrients [16:58] from outside your mitochondria and puts [17:00] them in. It also has a unique effect, [17:02] well, not too unique because tadalafil [17:04] actually has this effect as well, is [17:06] that it increases the density of the [17:08] androgen receptor in the cytoplasm of [17:11] your cells. [17:12] So, even if your androgen receptor [17:14] sensitivity doesn't change and even if [17:16] your testosterone does not change, you [17:19] will have more testosterone binding to [17:21] that increased number of receptors. [17:23] >> Does one need to cycle L-carnitine, [17:25] creatine, betaine? [17:27] >> No reason to cycle any of those. [17:29] >> What other supplements can one use to [17:31] try and improve hormone profiles? And [17:34] And here I realize we're using a very [17:36] broad brush, because when we say improve [17:37] hormone profiles, what are we really [17:38] talking about? And for me at least, I I [17:42] think about the subjective [17:44] um stuff. [clears throat] You know, do [17:45] people feel like they are going to have [17:47] more energy as a consequence of doing [17:49] these things? Are they going to have the [17:51] more optimized libido? Are they going to [17:53] have more optimized uh recovery from [17:55] exercise, right? Because I mean, it it's [17:57] not clear to me that taking one's [17:58] testosterone from 600 to 800 is always [18:01] going to be a good thing, especially if [18:02] estrogen is increasing in parallel. That [18:04] could cause issues. It could certainly [18:06] make things better. It could certainly [18:08] make things worse. [18:09] >> Right? [18:09] >> Let's briefly mention vitamin D, which [18:11] is also a hormone. It's actually a [18:12] sterol hormone. And have if you have [18:15] deficient vitamin D, and you replace it, [18:18] then you will optimize your [18:19] testosterone. [18:21] Let's also mention boron. So, if you [18:22] have a very high SHBG, boron can acutely [18:25] help lower it, usually in a dose of 5 to [18:27] 12 mg per day. It's not really a [18:30] sustained effect, but uh boron is [18:33] depleted in soils in many countries. I [18:35] believe it's very high in soils in [18:37] Greece and Turkey. So, eating dates or [18:39] raisins that are from those areas [18:40] potentially have more boron. Boron also [18:43] meet might be one of the reasons why the [18:45] reference range for testosterone is much [18:48] higher in those countries than other [18:50] countries. [18:51] >> And just to remind people that SHBG, sex [18:53] hormone binding globulin, is attaching [18:55] to the testosterone molecule and [18:57] limiting the amount of so-called free [18:58] testosterone that's available to have [19:00] its impact on cells. Okay, so vitamin [19:02] D3. I'm guessing you're talking about [19:03] vitamin D3 specifically when you say [19:05] vitamin D. And then boron, 5 to 12 mg [19:08] per day. Right? Um and then what are [19:10] some of the other things to optimize uh [19:13] testosterone that are in supplement [19:14] form? [19:15] >> We can talk about things that affect the [19:17] steroidogenesis cascade. So, we could [19:19] touch on tongkat ali. I know we've [19:20] talked about that a little bit before. [19:22] It's also [19:22] >> I'm guessing a number of people probably [19:23] haven't heard that conversation. [19:25] >> Also known as longjack, and that [19:27] upregulates several different enzymes in [19:30] the steroidogenesis cascade. And by [19:32] that, um, what you mean if, and this is [19:35] another good thing to Google. I think [19:36] anybody interested in hormone [19:38] optimization should understand where [19:40] where sterol hormones come from. They [19:42] come usually from cholesterol, and they [19:45] can be shunted off to vitamin D very [19:46] easily. They can be shunted off to [19:49] testosterone or estrogens or [19:51] progestogens quite easily as well. [19:54] But tongkat helps with the conversion of [19:57] multiple key steps where you synthesize [20:00] testosterone. [20:02] Another, um, [20:04] think of it as like a coenzyme or a [20:05] cofactor or an upregulator of these [20:07] steps is insulin and IGF-1. [20:11] So, a good rule of thumb is if you are [20:13] not expecting as much growth hormone, [20:15] insulin, and IGF-1, for example, lower [20:18] carb diets, caloric deficits, you're [20:21] trying to cut body fat or body weight, [20:24] then tongkat is going to be [20:26] theoretically especially powerful. [20:29] >> What sorts of dosages of tongkat do you [20:31] recommend to your patients? [20:33] >> Anywhere from 300 to 1,200 mg a day. [20:37] With tongkat, you need to be careful [20:40] with the standardization [20:42] because and if you're thinking about a [20:44] general tongkat supplement, which is by [20:46] far the most well-studied, [20:48] then, um, you're looking at the [20:50] eurycomanone content, which is a plant [20:53] compound that is likely the main, um, [20:56] active pharmacological effect. So, [20:58] that's the compound that's having the [21:00] effect on the body. [21:01] And if you standardize the eurycomanone [21:04] very, very high, then theoretically [21:07] you're having more effect at a lower [21:09] dose. [21:09] >> My blood work tells me that it causes an [21:11] increase in free testosterone for me, [21:14] and also a slight increase in [21:15] luteinizing hormone for me. Um what are [21:18] some of the other effects on various [21:20] hormones that you've observed in the [21:21] blood work of your patients taking [21:23] Tongkat Ali? [21:24] >> Tongkat can also slightly increase DHEA. [21:27] And if you have a very high SHBG, again, [21:30] that's the protein that binds up your [21:32] androgens and estrogens, an extremely [21:34] important protein. [21:36] Uh the higher your SHBG, the more it [21:38] helps decrease it. So, they've studied [21:41] Tongkat in uh [21:43] populations with very normal SHBGs, and [21:45] it does nothing for SHBG. [21:47] >> Interesting. Does that mean it does [21:49] nothing for somebody overall? So, if [21:51] somebody has SHBG that's in the normal [21:53] range, will taking Tongkat benefit them [21:55] in any other way? [21:57] >> Yes. It It'll increase their total and [21:59] free testosterone. [22:00] >> What are some of the other hormones that [22:03] you uh prescribe to your patients who do [22:06] not want to go on testosterone [22:07] replacement therapy or take exogenous [22:09] DHEA or anything like that? [22:12] >> We could talk about Fadogia next. Uh [22:14] Fadogia's interesting because it's a [22:15] genus of plants. Fadogia uh agrostis is [22:18] one of them. There's many others that [22:19] are very interesting. [22:21] Um that species is likely the most [22:23] well-studied, and it will increase LH. [22:26] So, [22:27] >> Luteinizing hormone. [22:28] >> I would not consider it an LH mimetic, [22:30] so it doesn't really mimic it, but it [22:31] increases the release of luteinizing [22:33] hormone from the pituitary It's a [22:35] hormone that binds to the Leydig cell, [22:38] to the LH receptor, kind of like hCG [22:40] does, [22:41] and it will increase the release of [22:43] testosterone. [22:44] >> What dosages uh do you have patients [22:47] take? I've heard of uh some potential [22:49] toxicity to the testicular cells. [22:52] >> There was one study, and this is a rat [22:53] study, but you can equate the dose of [22:56] toxicity in rats and humans. They did [22:58] not give these rats any antioxidants, [23:01] but it increases a couple different um [23:04] like pro-inflammatory markers. One is [23:06] GGT or gamma glutamyltransferase. [23:09] Comes from both the testes and the [23:10] liver, and one is alkaline phosphatase, [23:13] also known as alk phos, again coming [23:15] from both areas. [23:17] There are several different ways that [23:18] you can attenuate this increase, and you [23:20] can also just check to see if you have [23:21] increased. In the rat dose that equates [23:25] with humans that had no effect, so the [23:27] safe dose was an average of 300 [23:30] >> mg a day. So, that would be 300 mg a day [23:33] in humans is the dosage that did not [23:36] have toxicity. Correct? [23:37] >> Correct. And often, even if there is [23:39] toxicity in rats, there is not toxicity [23:43] in humans, so it's not directly [23:44] equitable, but to be safe, [23:47] um another regimen that I have people [23:49] take is 600 mg every other day or 600 mg [23:53] three times a week, often Monday, [23:55] Wednesday, Friday. [23:56] >> My understanding is that nowadays a lot [23:58] of people are using testosterone. Let's [24:00] not even call it replacement therapy, [24:01] because some of these people have 600, [24:03] 700, or even, you know, 800 ng per [24:06] deciliter leads. So, they're not [24:08] replacing anything that is diminished. [24:10] They're just trying to augment what's [24:11] already there, increase what's already [24:13] there. My understanding is that taking a [24:15] low dose more frequently is going to be [24:17] more beneficial than the kind of [24:19] old-school way of giving, you know, 100 [24:22] or even 200 mg in a single injection [24:24] once every 2 weeks. Is that right? And [24:26] And what do you do with your patients? [24:27] So, let me give you a hypothetical. [24:29] Somebody comes into your office, they [24:31] um you do their blood work, and they [24:33] have um [24:34] blood levels of [24:36] let's say 600 ng per deciliter [24:38] testosterone. Their estrogen is also in [24:40] normal range. Everything else checks [24:42] out, but they're complaining of, you [24:44] know, a slightly diminished libido, [24:46] slightly poor recovery from workouts, [24:48] maybe, um you know, reduced motivation [24:50] and drive, although no major depression, [24:53] and you come to the conclusion that [24:54] testosterone therapy, not replacement, [24:57] but testosterone therapy might be a good [24:58] option to explore. What's a typical [25:00] dosage range and frequency of [25:03] administration range that [25:05] you might consider exploring? [25:07] >> Some of this depends on the SHBG and [25:09] free testosterone as well. So, if that [25:10] same individual had a very high SHBG, [25:13] which again is the binding protein that [25:14] binds up the testosterone and all [25:16] androgens and estrogens, [25:18] if it is extremely high and they have a [25:20] free testosterone of two, [25:23] then they might need a different dose [25:24] because they need enough testosterone in [25:26] order to [25:28] have a normal eugonadal free [25:31] testosterone. [25:32] But, a general normal dosing range, [25:34] especially for someone starting, is [25:36] around 100 to 120 mg divided over the [25:40] course of a week, usually either every [25:43] other day or three times a week, [25:45] occasionally twice a week. Many people [25:47] with SHBG a bit higher can get away [25:50] pretty easily with twice a week. This is [25:52] assuming that the ester is cypionate or [25:54] enanthate. [25:55] >> So, two 60-mg injections of testosterone [25:58] cypionate per week. [25:59] >> Yeah, very common dosing. [26:01] >> To hit that 120 mg per week as kind of [26:03] the typical average. Correct. [26:04] >> And I would consider this like a [26:06] physiologic eugonadal dose. For many [26:09] people, even 200 mg a week is far above [26:13] the reference range. All of this is said [26:15] with the caveat that testosterone is [26:17] normally released in a pulsatile manner. [26:20] So, it's high in the morning, low in the [26:21] evening. Whereas, if you're on [26:23] testosterone therapy, then [26:27] you're going to have a steady state. So, [26:29] your testosterone level is going to be [26:31] pretty much the same even in the [26:33] evening. [26:33] >> In your experience, when patients do [26:35] that, they I'm guessing they report the [26:37] normal constellation of positive [26:38] effects, you know, improved mood, [26:40] improved energy, improved sleep, [26:41] recovery, etc. [26:43] What are some of the hazards or things [26:45] that um can crop up in blood work or [26:47] just subjectively that can be warning [26:50] signs that even a dosage of 120 mg [26:53] divided into these two or three dosages [26:55] per week can is too high. [26:56] >> So, this is when you really have to be [26:59] at least well-versed in every organ [27:02] system, not just the gonadal [27:05] like, you know, genital system. [27:07] You need to have, [27:09] you know, dermatology prowess. Acne is a [27:12] very common change. Lots of different [27:15] skin pathologies or even bruising can be [27:17] related to hormone replacement. [27:20] Hair loss is very common to see as well. [27:23] Mental status changes. It could [27:25] occasionally it even induces a manic or [27:27] a bipolar episode because testosterone [27:29] is also dopaminergic. [27:31] And then cardiovascularly, not just in [27:33] the heart, but also concerns for like [27:35] microvascular ischemic disease, ferritin [27:38] buildup because the estrogen also [27:40] increases. [27:41] And then fertility concerns as well and [27:44] lipid concerns, too. So, you really have [27:46] to be, you know, hematologist, [27:47] dermatologist, cardiologist, um [27:51] a lipidologist, the whole nine yards. [27:53] >> So, [27:54] another reason or set of reasons rather [27:57] to [27:58] uh [27:59] if one is considering using testosterone [28:01] therapy to really do this in close [28:03] communication with a really good [28:05] physician cuz that's a lot to monitor. [28:07] Knowing whether or not you have acne or [28:08] not is one thing. But knowing whether or [28:09] not your LDL is going up, your apoB is [28:12] going up, that's a whole other biz and [28:13] that needs to be done through blood work [28:15] is what I'm hearing. [28:16] >> Correct. And if your physician that is [28:18] managing or prescribing your [28:21] testosterone therapy or your HRT is not [28:24] well-versed in these systems, you would [28:26] want him or her to be part of an [28:28] interdisciplinary team where they have [28:29] other experts that can monitor those [28:31] systems. [28:32] >> There are males out there who want to [28:34] increase their testosterone [28:36] and other hormones, maybe growth [28:38] hormone, etc., who opt to not take [28:41] exogenous testosterone. So, no cream, no [28:43] pellet, no no pill, no injectable [28:46] cypionate, but decide to take clomiphene [28:49] a couple times a week. [28:52] My understanding, I've never done this, [28:53] I would say if I had, my understanding [28:55] is that [28:56] taking clomiphene [28:57] maybe two 50 mg tablets a week is what I [29:01] hear people are doing, will increase [29:03] what? Luteinizing hormone? [29:06] The various estrogen receptor subunits? [29:08] Could you explain how clomiphene would [29:09] benefit anyone and is this a good [29:11] strategy? I'm I'm hearing that it's [29:13] being done quite a lot now. [29:14] >> It will increase testosterone in a [29:16] dose-dependent manner, but it has many [29:19] other pharmacodynamic effects, which is [29:21] the effect of the drug on the body, [29:23] other than its effect on the [29:24] hypothalamus and the pituitary. So, in [29:26] the hypothalamus and the pituitary [29:29] it uh does what's called negative [29:31] feedback inhibition um or it it blocks [29:35] the action of estrogen. So, it crowds [29:38] out estrogen from the estrogen receptor [29:41] on the hypothalamus and the pituitary. [29:43] >> Why would I want to take something that [29:45] would increase the activity of an [29:47] estrogen receptor? [29:49] I just can't find the rationale for [29:51] that. [29:51] >> The main rationale behind taking a SERM [29:54] is as a very temporary measure that is [29:58] not going to suppress pituitary or [30:00] hypothalamic function if your [30:02] testosterone is just so drastically low [30:05] that it is unlikely to recover any what [30:08] anyway. So, most of the time it is not [30:11] clinically useful and um SERM should not [30:14] be prescribed very often, certainly not [30:16] as long-term testosterone replacement um [30:20] or testosterone optimization in most [30:22] individuals. There's always exceptions [30:24] to everything, [30:25] but um there's five different estrogen [30:28] and estrogen-related receptors. There's [30:31] two main estrogen receptors and clomid [30:34] and every SERM has a very unique profile [30:37] because they selectively inhibit some [30:40] receptors in some tissues, but not other [30:42] receptors in other tissues. For example, [30:45] um Clomid can inhibit receptors that are [30:47] in the eye, and it can cause um visual [30:50] changes, blurry vision, um especially at [30:54] higher doses. [30:56] And it also acts in every other tissue [30:58] of the body. So, side effects from [31:01] Clomid and other selective estrogen [31:03] receptor modifiers are very common. [31:05] >> Alcohol, does it increase aromatase, the [31:08] enzyme that converts testosterone into [31:10] estrogen, or not? And [31:12] um is there a dose dependence there? [31:14] >> It significantly does. There is a dose [31:17] dependence. In general, I would not [31:19] recommend more than [31:21] uh three to four, you know, standard [31:24] drinks. Uh one huge glass of wine is [31:26] probably five standard drinks every 2 [31:29] weeks. The other thing to keep in mind [31:30] with alcohol is it has a lot of [31:32] calories, 7 kcal per gram, almost as [31:35] much as fat, which is nine. And then [31:37] it's also very GABAergic, so it it it [31:40] can activate inhibitory [31:42] neurotransmission, um and that can also [31:45] affect how many how much uh LH and FSH [31:49] is released. So, that can also decrease [31:52] testosterone, almost kind of uh similar [31:55] to how opiates can decrease [31:57] testosterone. [31:58] >> I want to go back to the prostate and [32:00] talk to you about something that's kind [32:02] of a newer emerging trend. I know that [32:04] um you've talked to a little bit about [32:06] this in uh previous podcast, that a [32:08] number of men I should say a number of [32:10] physicians are [32:12] prescribing low-dose tadalafil, also [32:15] known as Cialis, to their male patients. [32:17] So, in dosage ranges of like 2.5 mg to 5 [32:20] mg per day, but not for erectile [32:22] dysfunction, but rather for improving [32:24] prostate health. And presumably they get [32:27] sort of a boost in terms of blood flow [32:29] um to the genitalia as well. But again, [32:31] not specifically to deal with uh [32:33] erectile dysfunction, but to deal with [32:36] prostate health and blood flow to the [32:38] prostate. Is that something that you [32:40] sometimes often prescribe to your [32:41] patients and of what age? [32:43] >> Tadalafil is a very underrated [32:45] medication. Um the age would kind of [32:47] depend on the indication. [32:50] So, tadalafil is also a blood pressure [32:53] medication. It can very slightly [32:54] decrease blood pressure, especially at [32:56] higher doses. [32:57] At higher doses, it theor- a a high dose [33:00] would be 20 mg, not 2.5 mg. But [33:03] consistently, it can somewhat affect [33:06] with the cones in the eye that have to [33:08] do with red and green sight. Although, [33:10] if you remove it, that effect is [33:11] reversed. So, basically, if you don't [33:13] need really really good red green [33:15] discrimination, you can take higher [33:16] doses. But in general, I recommend no [33:19] higher than 10 mg a day, usually just 2 [33:22] or 5 mg. [33:24] One uh other benefit or other use of [33:28] tadalafil is that it increases the [33:29] density of the androgen receptor, [33:32] similarly to L-carnitine. [33:35] So, that's an interesting benefit. [33:36] Another benefit is that if you give it [33:38] to people with nocturia, which is [33:40] urinating at night in general, it will [33:42] cut the episodes in half. So, it could [33:44] go from two to one, which can make a big [33:46] difference for your sleep, which will [33:48] secondarily make a big difference for [33:50] your growth hormone and testosterone [33:51] optimization. [33:52] >> Interesting. So, you said 2.5 to 5 mg [33:55] per day is kind of typical for these [33:56] prostate enhancing effects. [33:58] >> Yes. [33:59] >> I get a lot of questions about drugs to [34:02] offset hair loss. Most of those drugs [34:04] are going to operate through the DHT [34:06] system, the dihydrotestosterone system, [34:08] for the reasons we talked about before, [34:09] DHT receptors being on the scalp and uh [34:11] causing beard growth on the face. Is it [34:13] the case that a number of people taking [34:15] um things like Propecia and other things [34:18] to block DHT or disrupt the DHT pathway [34:22] are going to experience diminished um [34:25] sex drive, diminished um [34:27] you know, kind of motivation and general [34:29] vigor? And if so, are there alternatives [34:31] like topical DHT antagonists that they [34:33] might use um if they want to keep their [34:36] hair but not have those negative [34:38] effects? [34:39] >> Many people that have just a bit of [34:41] predisposition, they can use things that [34:43] are topical anti-androgens. [34:47] Ketoconazole is one of them. Caffeine is [34:49] actually another one. [34:50] >> Wait, you have to explain how this [34:51] works. How do people get caffeine into [34:54] the hair follicle? [34:55] >> Topically, the caffeine enters the scalp [34:58] and crowds out like somewhat crowds out [35:00] the androgen. It is a weak effect. It's [35:03] likely just strong enough to be [35:05] clinically significant. Usually, [35:07] caffeine is put into formulations with [35:09] other things like ketoconazole that are [35:12] also weak anti-androgens. Of note, [35:15] spironolactone can be prescribed [35:16] topically but is it is absorbed [35:18] systemically because the size of the [35:20] molecule. So, unless your doctor [35:22] specifically prescribes that for you, [35:24] especially as a male, do not use topical [35:26] spironolactone. [35:28] Topical finasteride is also a smaller [35:30] molecule, so it is also systemically [35:33] absorbed. But it is not extremely well [35:36] systemically absorbed. If you take [35:38] topical finasteride, then usually your [35:40] systemic DHT will decrease by about 30%. [35:44] Topical dutasteride [35:46] is likely a tiny bit systemically [35:48] absorbed but it's unique because its [35:49] half-life is much faster at a lower [35:51] dose. So, topical dutasteride will not [35:55] affect your systemic DHT at all and I've [35:57] seen this anecdotally on many people on [35:59] topical dutasteride therapy. [36:01] >> On behalf of the audience and and just [36:03] for myself, thank you so much. You have [36:05] an immense amount of knowledge and [36:06] you're exquisitely good at sharing it [36:08] with people in an actionable way. So, [36:10] thank you. [36:11] >> My pleasure. [music]