Cannabinoids (THC, CBD) don't directly reduce testosterone. Instead, the act of smoking marijuana increases the enzyme aromatase, which converts testosterone into estrogen. Higher estrogen then signals the pituitary to reduce testosterone production, creating an indirect negative feedback loop.

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The androgen receptor gene, which dictates how the body responds to hormones like testosterone and DHT, is located on the X chromosome. Since men (XY) inherit their X chromosome from their mother, their genetic predisposition for androgen sensitivity is maternally inherited.

Patients can successfully request hormone tests by describing subjective declines in energy, focus, or athletic performance compared to their past selves. This provides the necessary clinical justification for the lab work without requiring a pre-existing diagnosis.

The impact of caloric restriction on testosterone is context-dependent. While it can improve testosterone levels in men with obesity or metabolic syndrome, the same dietary stress will likely decrease testosterone in young, healthy, lean men.

The term "hormone resistance" was misleading. Researchers discovered that even in a castrate state, prostate cancer tumors produce their own testosterone locally. This maintained androgen receptor signaling, proving the disease was still "androgen addicted" and opening the door for new targeted therapies.

Casein, a primary protein in milk, can function as a mu opioid receptor agonist within the gut. This activity can lead to an increase in prolactin levels, which in turn can suppress dopamine and the hormones that stimulate testosterone production.

When addressing hormone imbalances, start at the base of the "hormone pyramid." Optimizing foundational hormones like cortisol (stress) and insulin (blood sugar) is essential, as they directly impact thyroid function and sex hormones like estrogen and testosterone.

While low testosterone can cause poor sleep, starting TRT can also lead to sleep issues. It drastically increases the risk of sleep apnea and can initially put the body into a hypersympathetic (fight-or-flight) state, disrupting sleep patterns.

Dr. D'Agostino gives his aging, neutered dogs a Selective Androgen Receptor Modulator (SARM) to stimulate muscle protein synthesis and maintain vitality. This approach is analogous to Testosterone Replacement Therapy (TRT) in humans, aiming to counteract the loss of skeletal muscle mass associated with aging and hormonal changes.

Contrary to popular belief, women's bodies contain substantially more total testosterone than estradiol. This misunderstanding arises because tests use different units (nanograms vs. picograms) or focus only on "free" testosterone, understating its overall prevalence and importance.

Counterintuitively, administering super-physiologic levels of testosterone can induce responses in certain castration-resistant prostate cancers. This strategy, called Bipolar Androgen Therapy, exploits the tumor's overexpressed receptors, turning a growth signal into a therapeutic vulnerability, though it remains a risky approach.