#291 ‒ The role of testosterone in males and females, performance-enhancing drugs, sustainable fat loss, supplements, and more | Derek, More Plates More Dates Pt.2

Derek is a fitness educator, the entrepreneur behind More Plates More Dates, and an expert in exogenous molecules commonly used and misused by bodybuilders and athletes. In this episode, Derek returns to the podcast to explore the impact of exogenous molecules on male and female health. He covers testosterone, DHT, DHEA, progesterone, clomiphene (Clomid), hCG, and various peptides, alongside updates from the FDA affecting peptide use. Additionally, he addresses the recent hype around increasing muscle mass through myostatin inhibition via follistatin gene therapy and supplementation. Additionally, Derek discusses the various strategies that bodybuilders use for losing fat while preserving muscle, including insights on weight loss drugs.

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We discuss:

• Testosterone and DHT: mechanisms of action, regulation of muscle growth, and influence on male and female characteristics [2:15];
• TRT in women: the complexities and potential risks associated with testosterone use in women [9:00];
• DHEA supplementation: exploring the benefits and risks for women, and the differing effects on men vs. women [22:00];
• The role of progesterone in both men and women, pros and cons of supplementation, the importance of tailored doses, and more [28:00];
• Measuring levels of free testosterone [37:15];
• The trend towards earlier interest in TRT, and the risks of underground sources of testosterone [42:00];
• The complexities and considerations surrounding the use of Clomid, E-Clomid, and hCG in TRT [46:00];
• Low testosterone: diagnosis, potential causes, treatment options, and other considerations [53:45];
• Growth hormone-releasing peptides: rationale and implications of the recent FDA categorization as high-risk substances [1:03:45];
• Follistatin gene therapy and myostatin inhibition for increasing muscle mass: the recent hype online, human and animal data, and the need for more research [1:14:45];
• Simple tips for lowering calorie intake and losing fat [1:32:30];
• Methods of sustainable fat loss with muscle preservation: insights gleaned from bodybuilders [1:40:00];
• Could prolonged fasting impact testosterone levels? [1:55:30];
• High-protein ice cream [1:57:00];
• Exploring fat loss supplements and drugs: L-carnitine, yohimbine, and more [2:02:15];
• Potential remedies for individuals experiencing metabolic dysfunction due to hypercortisolemia [2:12:30];
• The cornerstones of body composition improvement remain nutrition and exercise, even in the presence of exogenous testosterone [2:19:15];
• The importance of approaching health advice found online with a critical eye and a healthy dose of skepticism [2:23:30]; and
• More.

Testosterone and DHT: mechanisms of action, regulation of muscle growth, and influence on male and female characteristics [2:15]

• Last time we spoke, we covered a lot of ground, and yet somehow at the end of it, we felt like there was still a lot to talk about
• Hence we’re back
• Peter is going to do something unusual, which is he’s going to ask what Derek wants to talk about, as opposed to driving down his agenda
  • Peter has a bunch of things that he wants to talk about, but he’s curious as to where Derek thinks we should pick things up
• Derek thinks we covered a lot of stuff at a surface level and there might be some unanswered questions or ambiguity on some specifics when it comes to:
  • Am I a good candidate for hormone replacement?
    • How would I assess that?
  • Should I be worried before I get on it?
  • What kind of things should I look for?
• A lot of people don’t know who to trust or listen to
• Many people (including Peter) are teetering on the thought of exploring hormone replacement, and Derek wants to see what Peter’s thought process is for evaluating this

• It seems like in the last decade there’s been a lot more attention brought to the idea of testosterone replacement
• The role of testosterone as a drug of abuse in sports has tarnished in in a way that we don’t see on the female side
  • When we talk about hormone replacement for women with estrogen and progesterone, that doesn’t come with the same performance enhancing benefit
• Derek points out that it’s odd that testosterone is such a taboo thing when at the end of the day, it’s just a natural hormone that you produce

Other differences in hormone replacement for men versus women 

• Estrogen and progesterone are not scheduled drugs
  • They’re hormones and you can prescribe them without any limitation
  • They’re unscheduled by the DEA
• Conversely, testosterone is scheduled and much more highly regulated
  • The suggestion here is there’s potential for abuse that we presumably don’t see with estrogen and progesterone

Talk briefly about testosterone androgen receptors, how they work, the role of DHT, and what this does for muscle protein synthesis 

• Most people are aware of testosterone as the primary masculine hormone, but in reality, it’s produced in significant quantities in both genders
  • It’s just that men produce 10x that of women
• Both men and women also produce estradiol and DHT, but in different proportions and binding proteins
• At the end of the day, the action of these hormones in the body is the same in men and women
• Testosterone binds to the androgen receptor and induces gene expression
  • It causes muscle protein synthesis and other anabolic actions in the bone
  • It has psychoactive effects in the brain
• The only difference between the sexes is the magnitude to which this happen
• Testosterone also is what essentially determines how you sexually mature and differentiate as you enter adolescence
• You could realistically manually manipulate testosterone, and you see this in doping scenarios in sports and in bodybuilding males
• Ultimately, testosterone is the primary androgen that dictates muscle growth and anabolic activity in tissues, and the metabolites of it regulate a bunch of other things in the body

Testosterone is the primary androgen that men and women alike rely on, just in differing amounts 

• We’ve discussed on the podcast [episode #180] in great detail mechanistically what happens when testosterone binds to the androgen receptor and how that gets into the nucleus and how it impacts gene transcription for translation of protein 
• What’s interesting is that Derek mentioned DHT
  • DHT has a significantly higher affinity for the androgen receptor

Is there else you want to say about the role of DHT versus testosterone?

• To elaborate on what the word androgen means, what you derive from androgens are masculine characteristics
• The further on this spectrum of androgenicity, the more masculine and virilizing potentially in women it could be
• DHT is the hormone that drives this pathway to the extreme, and it is responsible (alongside testosterone) for maximal sexual differentiation maturation in adolescents 
• Mutations in the gene that encodes 5⍺-reductase (the enzyme that makes DHT) [affect the amount of DHT produced in the body]
  • Certain pseudo-hermaphrodites who don’t have DHT will end up lesser developed in the masculine spectrum than a normal functioning human with full DHT production
• One one end of the spectrum, you have males producing 10x the testosterone and also more DHT
• And then females much more estrogen proportionally to males (depending on where they’re at in their cycle) but 10x lower testosterone (and also much less DHT)

The ratio of androgens to estrogen essentially dictates if you are going to have male characteristics or female characteristics, and how much those characteristics are going to be exaggerated 

• Even if you’re a fully grown female, if you expose yourself manually to these hormones, you could push yourself in that direction

What a lot of people know about DHT: hair loss is a common side effect and it’s an important hormone that regulates how masculine you become as you grow up 

• There’s a critical window of exposure to DHT
  • Embryologically, exposure to testosterone and DHT have an enormous impact on sexual differentiation later in life

TRT in women: the complexities and potential risks associated with testosterone use in women [9:00]

Testosterone can be masculinization in women 

• Peter has a female patient who is on testosterone and for about a month, she didn’t read the directions correctly and was accidentally taking 10x the dose

{end of show notes preview}

Derek: More Plates, More Dates

Derek is a Canadian bodybuilder from Vancouver and the host of More Plates More Dates, a podcast, YouTube channel, and website. His YouTube channel has 1.39 subscribers, and he posts new videos almost every day. He uses these platforms to discuss men’s health, diving into the topics of bodybuilding, supplements, fitness, self-improvement, and more. [greatestphysiques.com]

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