Hormetic Endocrinology
Orthodox endocrinology treats hormone replacement as a problem of restoration: levels are low, so we raise them; the target is a steady state within reference ranges. This framing has served medicine well for hypothyroidism and hypogonadism alike. But it leaves unexplored a different question—whether strategic, cyclical perturbation of hormonal systems might produce adaptations that static replacement cannot. What I want to do here is construct a theoretical framework for that question, grounded in what the literature actually supports, honest about where speculation begins, and structured enough to generate falsifiable predictions.
This isn’t medical advice. It’s an exercise in thinking clearly about a domain where most public discourse oscillates between bodybuilding folklore and clinical conservatism, with little in between. My goal is to build a model that could, in principle, be wrong—and to specify what “wrong” would look like.
The Problem with Testosterone Replacement
Testosterone replacement therapy, as typically practiced, creates a dependency. Exogenous testosterone suppresses the hypothalamic-pituitary-gonadal axis through negative feedback: the brain senses adequate androgenic and estrogenic signaling, reduces gonadotropin-releasing hormone output, and luteinizing hormone drops. Without LH stimulation, Leydig cells in the testes atrophy over time. The longer the suppression continues, the more profound the atrophy, and the more difficult recovery becomes upon cessation.
An Alternative Pharmacokinetic Profile
Methandrostenolone—methandienone, Dianabol, dbol—is a 17alpha-alkylated derivative of testosterone. What makes it pharmacokinetically interesting is its half-life: 3–6 hours. This is an order of magnitude shorter than testosterone esters. Within 1–2 days of cessation, the drug is effectively cleared.
A 1977 study in the Scandinavian Journal of Clinical and Laboratory Investigation examined exactly this. Researchers gave endurance athletes methandienone at 5mg and 10mg daily for one month. The results were striking: 5mg daily suppressed mean plasma testosterone by 66%; 10mg daily suppressed it by 73%. But here’s the critical finding: testosterone levels returned to baseline within approximately 10 days of cessation. And 2–6 weeks after stopping, there was a statistically significant overshoot—mean testosterone levels exceeded pre-treatment baselines.
The Hormesis Hypothesis
Hormesis is the phenomenon where low doses of a stressor produce beneficial adaptations that larger doses would not. Applied to the HPG axis, my hypothesis would be:
Brief, cyclical suppression of endogenous testosterone production—followed by complete clearance and full recovery—may preserve or even enhance baseline HPG function over time, rather than degrading it as chronic suppression does.
Enter Thyroid: The Leydig Cell Connection
T3 receptors have been identified in Leydig cells, Sertoli cells, and germ cells. T3 directly increases LH receptor numbers on Leydig cells, upregulates steroidogenic acute regulatory protein (StAR), and increases mRNA levels of steroidogenic enzymes.
A Framework for Thinking About Synergy
Velocity and Stability
Velocity refers to metabolic and neural throughput—transcriptional speed, ion flux, mitochondrial activity, neural firing rates. This is primarily set by thyroid signaling. T3 is the accelerator pedal.
Stability refers to structural and regulatory buffering—protein retention, connective tissue integrity, calcium handling, synaptic robustness. This is significantly influenced by androgen signaling. Androgens are the chassis that keeps the car on the road as it accelerates.
What I Know, What I’m Guessing, What I Don’t Know
Well-Grounded
- T3 directly enhances Leydig cell steroidogenesis through documented pathways
- Methandienone at 5–10mg daily produces ~66–73% testosterone suppression
- Recovery occurs within ~10 days; supercompensation is observed at 2–6 weeks
- The short half-life (3–6 hours) enables rapid clearance
Speculative but Plausible
- T3 increases androgen receptor expression in skeletal muscle
- Conservative androgen support buffers calcium handling destabilization from T3
- Repeated hormetic cycles produce cumulative phenotype migration
Unknown
- Whether supercompensation persists across multiple cycles or attenuates
- Long-term hepatic effects of low-dose 17alpha-alkylated androgens
- Individual variation in response