The trough is not in dispute. Weekly testosterone enanthate produces mean nadir concentrations of 253, 306, 542, 1,345 and 2,370 ng/dL at 25, 50, 125, 300 and 600 mg respectively.[1] Concentration falls across the interval, and the dose determines how far.
The contested part is the next step: whether that fall is what a man is experiencing on day six.
The case that it is
Coherent, and worth stating at its strongest.
Effects track concentration. In the dose-response study, fat-free mass correlated with log testosterone concentration, and strength, muscle volume, hemoglobin and IGF-I were all positively correlated with concentration — with fat mass and HDL negatively correlated.[1]
The peak is documented, not just the trough. A randomised 24-week trial found 200 mg enanthate IM every two weeks produced supraphysiological testosterone, bioavailable testosterone and estradiol for several days after each injection, against a transdermal arm that stayed within physiological range.[4]
The preparations are acknowledged to be imperfect. All injectable esters used clinically were characterised as having unfavourable pharmacokinetics against the goal of constant physiological levels.[2]
The reports are consistent. Many men describe the same pattern, unprompted.
The case that it is more complicated
From the same study, and this is the awkward part.
Sexual function, mood, visual-spatial cognition and PSA did not change significantly at any dose — across nadir concentrations from 253 to 2,370 ng/dL.[1]
That is a nearly tenfold range of trough levels with no significant difference in mood or sexual function. If trough depth drove those symptoms straightforwardly, that is not the expected result.
Two caveats in the other direction: the participants were healthy young men with normal baseline mood and sexual function, leaving limited room to improve, and the study ran 20 weeks.[1] It was not designed to measure how hypogonadal men feel across a weekly cycle.
What is worth doing about it
Report the pattern. A reproducible symptom cycle tied to dosing is clinical information, and it is a reason to review dose, interval or formulation.
Do not raise the dose reflexively. Lifting the trough by raising the peak brings hemoglobin up and HDL down,[1] and the guideline's target is mid-normal, not the top of the range.[3]
Check the level is actually at target. Being mid-normal rules out under-dosing as the explanation, which usefully redirects the search.
Time the draw properly. With interval dosing, a level means nothing without knowing where in the cycle it was taken — see the 3-month panel.
Frequently asked questions
Is the day-six feeling real? The experience is reported consistently, and both the peak[4] and the trough[1] are measured. The causal link to symptoms has not been established — the randomised comparison found mood and sexual function maintained on either profile.[4]
Would more frequent dosing fix it? Pharmacokinetically it narrows the swing, and weekly subcutaneous dosing held levels stable across the interval in a small study.[5] Whether that changes symptoms is the untested part — daily vs weekly dosing.
Should I split my weekly dose myself? A conversation with your prescriber, not a self-adjustment.
Could it be something else? Worth considering. Sleep, mood and other causes produce the same symptoms and are covered in fatigue and sleep.
Next in this series
The word attached to the proposed solution deserves examining.
Continue with microdosing testosterone.
References
5 sources
- Bhasin S, Woodhouse L, Casaburi R, et al. Testosterone dose-response relationships in healthy young men. Am J Physiol Endocrinol Metab. 2001;281(6):E1172–E1181. doi:10.1152/ajpendo.2001.281.6.E1172 · PMID 11701431
- Partsch CJ, Weinbauer GF, Fang R, et al. Injectable testosterone undecanoate has more favourable pharmacokinetics and pharmacodynamics than testosterone enanthate. Eur J Endocrinol. 1995;132(4):514–519. doi:10.1530/eje.0.1320514 · PMID 7711892
- Bhasin S, Brito JP, Cunningham GR, et al. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018;103(5):1715–1744. doi:10.1210/jc.2018-00229 · PMID 29562364
- Dobs AS, Meikle AW, Arver S, et al. Pharmacokinetics, Efficacy, and Safety of a Permeation-Enhanced Testosterone Transdermal System in Comparison with Bi-Weekly Injections of Testosterone Enanthate for the Treatment of Hypogonadal Men. J Clin Endocrinol Metab. 1999;84(10):3469–3478. doi:10.1210/jcem.84.10.6078 · PMID 10522982
- McFarland J, Craig W, Clarke NJ, et al. Serum Testosterone Concentrations Remain Stable Between Injections in Patients Receiving Subcutaneous Testosterone. J Endocr Soc. 2017;1(8):1095–1103. doi:10.1210/js.2017-00148 · PMID 29264562
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