Do Serum Testosterone Values Potentiate or Predict Muscle Hypertrophy?

Do Serum Testosterone Values Potentiate or Predict Muscle Hypertrophy? A Structured Narrative Review

Abstract

Testosterone is the prototypical anabolic-androgenic hormone, and circulating concentrations in men are widely assumed to predict the magnitude of resistance-training (RT)-induced hypertrophy. The available current evidence does not support this assumption. This structured narrative review synthesizes the evidence relating testosterone levels to RT-induced hypertrophic responses across the full testosterone spectrum, from exogenously administered dose-response trials to eugonadal training cohorts, androgen-suppression and androgen-deprivation trials, and the female parallel. We propose a three-phase model of the testosterone-hypertrophy relationship: (i) a permissive lower-bound threshold below which low testosterone constrains, but does not eliminate, the hypertrophic response from resistance training; (ii) a null, non-predictive zone across the male eugonadal range; and (iii) a graded, dose-dependent augmentation of hypertrophy from exogenous testosterone. These different phases reflect a concentration- and source-dependent relationship that is misrepresented when testosterone is modeled as a single continuous driver of muscle growth. In summary, testosterone appears permissive within the normal male range, blunted in extreme deprivation, and a graded driver when administered exogenously; normal inter-individual variation inside the eugonadal range does not appear to meaningfully predict RT-induced hypertrophic potential in men.

Keywords: testosterone; hypertrophy; resistance training; androgen receptor; narrative synthesis; threshold model; androgen deprivation therapy

1. Introduction

Testosterone's reputation as the master anabolic hormone has influenced decisions well beyond the laboratory, informing resistance training interventions, the prescribing of testosterone-replacement therapy, and even the clinical management of hypogonadism and androgen deprivation. Testosterone acts on skeletal muscle principally through the androgen receptor (AR), a ligand-activated transcription factor expressed in muscle fibers and satellite cells. Androgen binding promotes satellite-cell activation and proliferation, the accretion of new myonuclei to growing fibers, and augments muscle protein synthesis [1-3]. These mechanisms establish clear biological plausibility for a dose-dependent anabolic effect and account for the reliable accretion of muscle mass under exogenous testosterone conditions. Because androgen administration expands the satellite-cell pool and likely adds myonuclei in proportion to the dose, these cellular events also provide a mechanistic basis for the graded response to exogenously administered testosterone. They establish, however, only that exogenously administered androgen exposure is anabolic; they do not establish that variability within the comparatively narrow eugonadal range of endogenous testosterone is sufficient to modulate these pathways.

Despite this, there has historically been an assumption that higher testosterone levels invariably lead to increases in muscle mass across and, by extension, that endogenous testosterone concentrations will predict resistance-training (RT)-induced hypertrophy. This review explores whether that ideology is supported by the evidence across the entire testosterone concentration spectrum. It first characterizes the dose-response to exogenous testosterone, then synthesizes the relationship between baseline endogenous testosterone and hypertrophy in eugonadal men, and finally examines what happens below the eugonadal floor, before drawing a brief parallel to the female literature.

2. Materials and Methods

Studies were identified from the author team's working knowledge of this literature, supplemented by database searching. PubMed/MEDLINE was searched using two Boolean strategies combining androgen-exposure terms (baseline, basal, resting, endogenous, and free testosterone; androgen) with training terms (resistance training, strength training, resistance exercise, weight lifting) and hypertrophy outcomes (hypertrophy, cross-sectional area, lean body mass, fat-free mass, muscle thickness, muscle mass). Keyword retrieval alone is insufficient for this literature as baseline testosterone is a covariate in these cohorts rather than their subject and is frequently absent from the indexed record.

Cohort inclusion required: (i) longitudinal resistance training in healthy eugonadal men; (ii) baseline serum androgen measurement; (iii) a quantitative hypertrophy outcome (fiber cross-sectional area, MRI or ultrasound muscle cross-sectional area, DXA lean body mass, or ultrasound muscle thickness); and (iv) an analysis relating baseline androgen status to that outcome, either reported in the source or derived here from archived individual-participant data. Studies that did not report a baseline serum testosterone measurement were excluded. These criteria govern the eugonadal correlational synthesis; the exogenous GnRH-clamp dose–response trials and the androgen-suppression and androgen-deprivation trials examined in Sections 3.1 and 3.3 constitute separate evidence streams with their own designs and were not subject to the eugonadal-cohort criteria above.

Findings were extracted using a three-tier hierarchy: tier 1 — Pearson correlations computed directly from publicly archived individual-participant raw data (Mobley et al. 2018 [4], S2 File; Haun et al. 2019 [5], Data Sheet 1); tier 2 — directly reported continuous association statistics from published manuscripts; tier 3 — narrative or indirect association reporting, including backward-eliminated regression terms, unspecified-magnitude null statements, or extreme-group comparisons. Where the same cohort underpinned multiple publications (i.e. Morton et al. 2016 [6] and 2018 [7]; Räntilä et al. 2021 [8] and 2023 [9]; McCall et al. 1996 [10] and McCall et al. 1999 [11]), it entered the synthesis only once.

The authors used Claude (Anthropic; version to be specified at acceptance) for coding assistance and computational support: writing the Python (matplotlib) and R scripts that render Figures 1–5 from numeric values, statistical re-derivation of the tier-1 correlations from archived individual-participant data (Mobley 2018; Haun 2019), assisting with extraction of tabulated and graphically reported values from the primary sources, and language editing. All figures were produced by conventional plotting code from author-verified data; no generative image-synthesis or image-manipulation tools were used. All AI-assisted outputs were reviewed and verified by the authors against the primary sources, and the authors take full responsibility for the content.

3. Evidence Across the Testosterone Spectrum

3.1. Exogenously Administered Testosterone and a Graded Dose–Hypertrophy Response

The ideology that "more testosterone equals more muscle" has dominated both lay and clinical thinking about anabolism for decades, and this belief is not unfounded. When testosterone is administered exogenously across a wide dose range under conditions of suppressed endogenous production (e.g., due to gonadotropin-releasing hormone (GnRH)-agonist clamping), lean body mass and muscle strength rise in a clear log-linear dose-response relationship. This has been demonstrated in graded-dose trials, both in young [3] and in older men [12], across five doses (25, 50, 125, 300, 600 mg/week). A follow-up trial using dutasteride co-administration further confirmed that conversion to dihydrotestosterone (DHT) is not essential to testosterone's anabolic effect on skeletal muscle [13]. Across all 14 dose arms of the three GnRH-clamp studies the slope of hypertrophy was +1.81 kg of lean mass per doubling of weekly dose (R² = 0.98, k = 14, 95% CI +1.65–1.97 kg/doubling; see Figure 1).  At supraphysiologic doses (≥300 mg/week) the negative feedback loop suppresses endogenous testosterone to near-castrate levels within weeks regardless of any GnRH agonist [14]. However, at sub-replacement doses (25–125 mg/week), the small exogenous contribution does not fully suppress luteinizing hormone (LH) and continued endogenous production could mask the dose-response. 

Foundational evidence for this hypertrophic mechanism comes from Bhasin et al. [14], which used a 2×2 factorial design (placebo vs 600 mg/week testosterone enanthate with either no exercise or supervised resistance training) in 43 randomized healthy young men aged 19–40 years over 10 weeks. Fat-free mass changed by approximately +0.8, +1.9, +3.2, and +6.1 kg in the placebo + no-exercise, placebo + RT, testosterone + no-exercise, and testosterone + RT arms, respectively in the 40 men who completed the trial. These findings indicate that supraphysiologic testosterone is anabolic on its own, as indicated by the 3.2 kg gain in men administered testosterone with no RT, and that exogenous testosterone and resistance training may operate additively rather than synergistically, given that the observed combined gain of +6.1 kg is within statistical error of the simple sum of the independent effects of testosterone and RT, i.e. +5.1 kg from the testosterone + no exercise and placebo + RT. However, this combined effect of testosterone and RT has not been directly replicated, and it remains unknown whether testosterone might synergistically augment the hypertrophy response induced by RT alone. 

Two physiological considerations explain why exogenous testosterone produces such consistent gains. First, weekly intramuscular esters eliminate the normal diurnal rhythm, holding serum testosterone at a stable, often supraphysiologic, plateau rather than oscillating between morning peak and evening trough levels [15]. Second, the androgen receptor (AR) does not appear to undergo pronounced downregulation with exogenous androgen exposure; supraphysiological testosterone modestly increases AR protein in cultured human satellite cells and increases nucleolar AR density in vivo [2]. The practical implication is that escalating exogenous testosterone doses do not seem to run into a receptor-saturation ceiling within the studied range, and the dose-response curve continues to rise well into supraphysiologic levels which aligns with the high dosing strategies (often times exceeding 600 mg per week which was the highest dose in the included studies) and the extreme levels of muscle mass seen in enhanced bodybuilding [16-18]. However, the changes in lean body mass and fat mass from exogenous testosterone administration at normal replacement dosages do not appear to persist indefinitely with continued treatment: across 42 months of continuous transdermal testosterone in 163 hypogonadal men, lean body mass gains and fat mass losses were established early in treatment and then maintained without further progression, consistent with the broader observation that exogenous testosterone establishes a new steady-state body composition rather than driving open-ended muscle accretion [19].

Figure 1.  Exogenous testosterone dose–response for lean body mass. Fourteen study arms from three GnRH-agonist-clamped graded-dose trials: Bhasin 2001 (young men; all 5 arms; underwater weighing - UWW) [3], Bhasin 2005 (older men; all 5 arms; dual-energy X-ray absorptiometry - DEXA) [12], and the placebo-plus-testosterone arm of Bhasin 2012 (4 arms; DEXA) [13]. (A) Across pooled study arms, lean body mass (LBM) demonstrated an approximately log-linear association with weekly dose: approximately +1.81 kg per doubling. (B) In the same trials, concurrent fat-mass decline is seen: approximately 1.00 kg per doubling. No obvious receptor-saturation plateau is apparent within the studied dose range; the linear LBM trend persists into supraphysiological territory. Subjects did not perform resistance training. The fat-mass regression pools Bhasin 2001 + Bhasin 2005 tabular values (DEXA fat mass for all three studies) with four Bhasin 2012 placebo arms were digitized from Figure 2 of the original paper utilizing WebPlotDigitizer, since per-dose fat-mass kg values are not reported in the main-text tables. Digitization carries ~ ±0.5 kg point-reading uncertainty, reflecting axis-calibration error and marker size during graphical extraction. Pooled fat-mass estimates should therefore only be interpreted descriptively.  Notably, the dose–response is considerably tighter for lean-mass accretion, consistent with a more direct anabolic action on skeletal muscle than on adipose tissue.

3.2. Dismantling the Hormone Hypothesis Within the Eugonadal Range

Exogenous testosterone appears to be quite anabolic, but that does not mean that endogenous variation in testosterone, whether acute post-exercise spikes or stable baseline differences between individuals, will also predict hypertrophic outcomes. A series of carefully designed studies over the past 15 years has systematically disproved the acute hormone hypothesis with compelling evidence from West and colleagues [20], who trained one arm of healthy young men under a low-hormone (isolated elbow flexor) protocol and the contralateral arm under a high-hormone (arm-plus-leg) protocol. The high-hormone protocol produced significant but transient peaks in testosterone, growth hormone, and insulin-like growth factor 1 (IGF-1) that crested ~15 min post-exercise and resolved within ~60 min, whereas the low-hormone protocol produced no detectable rise in any of the three hormones. Despite this sharp divergence in the post-exercise milieu the hypertrophic response was statistically indistinguishable between conditions and correlational cohorts have largely shown no relationship between the acute hormonal response and subsequent hypertrophy [20-22]. Post-exercise elevations of testosterone of around 10-30% typically last under 30 to 60 minutes, representing an area under the curve (AUC) that is likely trivial compared with normal endogenous testosterone secretion, which is therefore probably too small of a perturbation to drive any meaningful adaptive signal (see Figure 2) [23-26]. Furthermore, much of this post-exercise rise in testosterone may be due to exercise induced hemoconcentration as studies correcting for changes in plasma volume suggest that this may account for a significant portion of the increases seen in post-RT testosterone concentrations [26-28].

Figure 2. Acute post-exercise testosterone dynamics versus 24-hour integrated exposure. Diurnal rhythm of serum total testosterone in young men, redrawn from data reported in [29,30]. A resistance-exercise bout at 17:00 raises total testosterone ~10–30% above the concurrent baseline (peak ~463–547 ng/dL), no longer statistically detectable beyond ~30 min while remaining below the morning endogenous resting level. Solid red curve (with shaded fill) is the modeled +20% post-exercise rise that is integrated for the 24-h excess. The dashed red curve is the +30% ceiling of the reported 10–30% range. Integrated over 24 h the transient testosterone increase adds only ~0.1–0.3% to androgen exposure. Post-exercise dynamics redrawn from data reported in [23-26,31].

With respect to chronic endogenous exposure, it is often assumed that men with naturally higher baseline testosterone gain more muscle from RT. We reviewed six independent cohorts (total n = 195, of whom 179 contributed a baseline total-testosterone value) that measured baseline serum androgens in relation to subsequent RT-induced hypertrophy in either untrained or previously trained eugonadal men [4-11,32]. The descriptive characteristics of all included studies, and the per-cohort findings, are shown in Table 1. Findings are presented as a structured narrative table rather than as pooled effect sizes because only two of the six contributing cohorts (Mobley et al. 2018 [4]; Haun et al. 2019 [5]) reported extractable per-study associations or effect sizes from individual-participant data, while the others describe their basal testosterone findings as backward-eliminated regression terms (Morton et al. 2016 [6]and 2018 [7]), or narrative statements suggesting no relationship but without a reported r value (linear correlation coefficient) or effect estimate. A further cohort, Räntilä et al. 2021 [8] and 2023 [9], measured basal total testosterone but never modeled it directly against a hypertrophy outcome. The narrative-statement category therefore comprises the unquantified null of McCall et al. 1999 [11] and the responder-versus-non-responder subgroup comparison of Peltonen et al. 2018 [32].

Across the five cohorts that modeled baseline total testosterone against a hypertrophy outcome, none found a significant association. In Mobley et al. 2018 (n = 55), re-analysis of the archived individual-participant data yields r = +0.055 for baseline total testosterone versus Δ total fiber cross-sectional area (fCSA, p = 0.69) [4]; the corresponding value in Haun et al. 2019 (n = 26) is r = −0.049 (Δ avg fCSA, p = 0.81) [5]. Neither correlation appears in the source articles; both were computed here from the archived individual-participant data. Substituting dual-energy X-ray absorptiometry (DXA) lean body mass for fiber CSA in the Haun et al. 2019 [5] cohort reversed the direction of the association. Higher baseline testosterone predicted smaller lean-mass gains, opposite to what the hormone hypothesis would predict, reaching significance for absolute change (r = −0.41, p = 0.038), but not for percentage change (r = −0.36, p = 0.07). McCall et al. 1996 [10] and 1999 [11] correlated resting serum testosterone against the relative degree of hypertrophy in both biceps brachii cross-sectional area (n = 8) and muscle fiber cross-sectional area (n = 11) in recreationally trained college men after 12 weeks of training, and reported no significant association with either outcome, although no coefficient or p value was published. Among the six included cohorts free testosterone was measured in two: directly by Morton et al. 2016 [6] and 2018 [7], and calculated using the Vermeulen equation by Peltonen et al. 2018 [32]. It was modeled against a hypertrophy outcome in both; neither reported an association, and neither published a significant positive correlation. Across 48 stepwise regressions spanning ten hormones and three hypertrophy outcomes, Morton et al. found no hormone, baseline total testosterone included, to be a consistent predictor, with all model R² values below 0.25 [7]. 

The only two positive signals in the literature emerged when the predictor shifted from circulating concentration to androgen bioavailability. Räntilä et al. 2021 [8] and 2023 [9] did not measure or calculate free testosterone but instead reported the testosterone-to-SHBG ratio as a bioavailability proxy. They reported a borderline trend (r = +0.365, p = 0.079) between training-period averaged T/Sex-Hormone Binding Globulin (SHBG) ratio and change in vastus-lateralis cross-sectional area (Δ VLCSA; n = 24). Similarly, Peltonen [32] reported the baseline free androgen index (FAI) as 34% higher in responders versus non-responders (p = 0.019); the underlying baseline values are 69 ± 28 (MS-responders) and 98 ± 19 (P-responders) versus 56 ± 13 in non-responders. Because baseline total testosterone did not differ across those subgroups (750 / 721 / 721 ng/dL), the FAI difference is driven principally by SHBG (39 / 27 / 44 nmol/L) only in the P-responder subgroup, and Vermeulen-calculated free testosterone derived from the same two inputs was null. However, as only two cohorts appear to have measured bioavailable indices, and the predictor specifications differ between them, a formal quantitative meta-analysis of FAI or T:SHBG ratio would not be viable. 

Thus, across both training states (105 untrained and 90 previously-trained participants) the variation in baseline total testosterone within the eugonadal range (≈ 447–894 ng/dL including the Morton 2018 [7] subgroup means) was not found to predict the magnitude of subsequent hypertrophic response. In other words, these combined data suggest that two young eugonadal men positioned at opposite ends of the eugonadal reference window could begin a resistance training program and gain statistically indistinguishable quantities of lean body mass. Consistent with this, analyses from the same field find that baseline androgen status does not separate those considered high responders to RT versus low responders. Mobley et al. 2018 [4] identified no hormonal biomarker (including testosterone) distinguishing response clusters. This lack of relationship is therefore consistent across training states, with Mobley et al. [4] (untrained, r = +0.055) and Haun et al. [5] (previously trained, r = −0.049) both bracketing zero from opposite directions.

Table 1.  Descriptive characteristics of the six cohorts included in the narrative synthesis. Each row describes one independent cohort relating baseline serum testosterone to subsequent RT-induced hypertrophy. In addition to participant and training characteristics, the table summarizes methodological features relevant to interpretation, including androgen assay approach, blood-sampling and dietary standardization, free-testosterone/bioavailability assessment, hypertrophy endpoint, and key sources of potential bias. Total pooled sample n = 195 (untrained = 105; previously strength-trained = 90); 179 participants contributed a baseline total-testosterone value. Morton et al. 2016 and 2018 are the same n = 49 cohort, collapsed. McCall et al. 1999 and 1996, Räntilä 2021 2023, also report the same cohort and are likewise collapsed.

Finding columns: § age computed from the study’s publicly archived raw individual-participant data. † detail not stated in the source (time-of-day standardization for Haun; age ± SD for the Räntilä n = 24 analysis subset, which the source reports only for the 26 enrolled; age ± SD for McCall, which the source reports only as an 18–25 y range). AR, androgen receptor; CSA, cross-sectional area; DXA, dual-energy X-ray absorptiometry; FAI, free androgen index; HR/MR/LR, high/medium/low responders; IPD, individual-participant data; MS, maximum-strength responders; NA, non-strength athletes; NR, not reported; P, power responders; RFD, rate of force development; SA, strength athletes; SHBG, sex-hormone-binding globulin; VL, vastus lateralis.

3.3. The Lower-Bound Discontinuity

The clear dose-response relationship between exogenous testosterone administration and hypertrophy, set against the absence of an association between endogenous testosterone and RT-induced hypertrophy within the eugonadal range, leaves a final question: what happens below the eugonadal floor? Two randomized controlled trials in healthy eugonadal men have addressed this directly, pharmacologically suppressing endogenous testosterone production with the GnRH agonist goserelin and then exposing suppressed subjects to a conventional RT program. Kvorning et al. 2006 (n = 22, 8 weeks RT during 12 weeks of goserelin) reduced serum testosterone from ~652 ng/dL to ~32 ng/dL, a castrate concentration sustained across the entire training block. The suppressed arm gained 1.3 kg of LBM versus 2.3 kg in placebo, a 43% attenuation of the eugonadal training response (between-group difference for whole-body LBM p = 0.07; the parallel comparison for leg LBM p = 0.05, at +0.37 vs +0.57 kg) [33]. Companion analysis of the same cohort found no treatment effect on muscle mRNA expression for the IGF-1 isoforms, myogenin, myoD, myostatin, or the androgen receptor, though on fewer subjects and with sampling that stopped at 24 h [34]. Gharahdaghi et al. 2022 (n = 16 eugonadal young men, 6 weeks RT following a single goserelin injection) extended this finding with deeper mechanistic phenotyping: LBM rose by 1.5 kg in the placebo arm (p = 0.006), but only 0.4 kg under suppression (p = 0.61; treatment-by-time interaction p = 0.04), a 73% attenuation, with parallel blunting of muscle protein synthesis and composite strength [35] (see Figure 3). Interestingly, the placebo group in Gharahdaghi that showed significant LBM gains maintained a serum testosterone of roughly ~320 ng/dL. The testosterone suppressed group levels in the Gharahdaghi dropped to a nadir of ~45 ng/dL, which is similar, but not as low as of a testosterone suppression compared to Kvorning et al. [33]. The two trials diverge molecularly, as Kvorning et al. reported equivalent expression across conditions, whereas Gharahdaghi reported attenuated upregulation of androgen receptor, IGF-1Ea/Ec, and myogenin, alongside blunted Akt and mTORC1 in the suppressed condition. This leaves the unresolved question. Under suppression, are subjects losing muscle to acute hypogonadism while simultaneously regaining some through the RT stimulus, are they responding through a globally blunted anabolic transduction system, or even more complicated, some combination of the two? The current available data cannot confidently distinguish between these mechanisms, but Gharahdaghi's data favor the second, although both of these trials involve small sample sizes and the Gharahdaghi was relatively short for an RT-induced hypertrophy study. Thus, it does appear that males can gain significant amounts of muscle mass at lower testosterone levels with resistance training and this is corroborated by Longland et al. who found that males in the higher-protein group increased lean body mass by 1.2 ± 1.0 kg while fat mass fell by 4.8 ± 1.6 kg (measured via a four-compartment model) over the four weeks at a 40% energy deficit, while total testosterone dropped from 507 ± 23 to 126 ± 19 ng/dL [36]. However, it does appear that without resistance training testosterone suppression in males does result a significant loss of LBM (~2kg in 10 weeks measured via skin calipers) [37]. Muscle loss was also seen in 198 goserelin-suppressed men over 16 weeks, where total-body lean mass (DEXA) and thigh-muscle area (computed tomography) were preserved in arms achieving 337 ng/dL or more but declined in those achieving 44 ± 13 and 191 ± 78 ng/dL [38].

Furthermore, the prostate-cancer androgen-deprivation therapy (ADT) literature provides a large-scale confirmatory dataset for the lower-bound interpretation. Shao et al. 2022 meta-analyzed 12 randomized controlled trials (RCTs) (n = 715) of exercise training (resistance, aerobic, or combined) versus usual care (continued ADT and routine clinical management without a structured exercise program) in men on ADT, and found a pooled 0.88 kg LBM advantage (95% CI +0.40 to +1.36) a 0.60 kg fat mass loss, and a 0.93% body fat reduction in the exercise arms [39]. Moreover, representative individual trials from multiple research streams [40-43] show that RT in hypogonadal men can recover meaningful lean mass, but the magnitude (~ 0.9 kg over 12–20 weeks) is below the 2.3 kg in eugonadal placebo + RT cohorts seen in the studies cited above [33]. Nonetheless, this finding is at least close to the meta-analytic data showing that RT induces hypertrophy outcomes of approximately +1.53 kg (95% CI +1.30 to +1.76 kg) over an average intervention of roughly 10 weeks in duration [44]. These pooled effects are convergent across independent subsequent meta-analyses. For example, Tian et al. 2022 reported +1.12 kg total lean mass and +0.74 kg appendicular skeletal mass advantages for RT in hypogonadal men treated with ADT [45]. Similarly, Lopez et al.’s 2023 individual-patient-data meta-analysis (n = 560) confirmed significant gains in whole-body and appendicular lean mass in response to RT under ADT, with greater benefit observed specifically in younger patients [46]. Taken together, these studies suggest that RT-induced hypertrophy is indeed possible in a medically induced androgen deprived state. However, it’s worth noting that these meta-analyses report related but non-identical DXA endpoints including whole-body lean body mass [39], total lean mass and appendicular skeletal mass [45] and whole-body plus appendicular lean mass [46], where appendicular measures capture limb skeletal muscle only and are not interchangeable with whole-body lean mass. 

Figure 3.  Lower-bound discontinuity: the RT response in acute and chronic hypogonadism. (a) Kvorning 2006 [33] — Pharmacological suppression of testosterone (goserelin, T ≈ 32 ng/dL) blunted the LBM response to 8 weeks of resistance training by 43% relative to the eugonadal placebo arm. (b) Gharahdaghi 2022 [35] — A 73% attenuation in fat-free mass after 6 weeks of resistance training exercise under Zoladex suppression, with parallel blunting of muscle protein synthesis and AR/mTOR signaling. (c) Shao [39] meta-analysis (k = 12 RCTs, n = 715) — The chronic androgen deprivation therapy cohorts gained +0.88 kg of lean mass with mixed-modality exercise (resistance, aerobic, or combined) versus usual care, a positive but markedly attenuated training response. Figures redrawn from data reported in the respective studies.

A revealing thought experiment compares two extremes within this paradigm (see Figure 4). With exogenous testosterone administration at 25 mg/week in Bhasin et al. 2005 [12] resulting in a serum testosterone of ~ 175 ng/dL (one week after the injection), which is well below the clinical hypogonadal floor (~ 264 ng/dL by the Endocrine Society reference range [47]). Over 20 weeks without RT, participants lost 0.3 kg of LBM [12]. In the goserelin arm of Kvorning et al. 2006, with serum testosterone suppressed to approximately 32 ng/dL (roughly one-fifth as much circulating androgen) but with RT added, those individuals gained an average of 1.3 kg of LBM [33]. The same trichotomy is visible in the converse direction: at ~275 ng/dL one week after the injection without RT (Bhasin et al. 2005 [12], 50 mg/week arm), participants gained 1.7 kg, while at 640 ng/dL with RT (Kvorning et al., placebo arm) men gained 2.3 kg. Reading across these data, the training stimulus seems to account for a 1.3-2.3 kg LBM gain from near-total androgen suppression to eugonadal placebo over the eight-week resistance training period [33]. By comparison, exogenously dosed testosterone clearly influences the amount of muscle mass gained without RT, and testosterone values within the low-normal to eugonadal range even appear to increase the LBM gains from RT rather than determine the existence of an adaptation. Along these same lines, cross-sectional associations between eugonadal-range testosterone and baseline muscle mass are small and direction-inconsistent across cohorts [48,49]. More precisely, longitudinal and Mendelian-randomization evidence indicates that body composition affects testosterone more than testosterone affects body composition [50,51]. A recent review reaches the same conclusion, noting that changes in adiposity exert marked effects on the hypothalamic–pituitary–testicular axis whereas changes in circulating testosterone have comparatively modest effects on body composition [52].

Figure 4.  Dissociation between serum testosterone and lean-mass change as a function of resistance training. Four data points are displayed on a common axis: two non-training arms from the Bhasin 2005 [12] dose-escalation ladder (red circles, no RT) and two training arms from Kvorning 2006 [33] (blue squares, with RT). Across an approximately 20-fold span of serum testosterone, the presence or absence of RT accounts for far more of the variance in LBM changes than testosterone level per se. At T ≈ 32 ng/dL, RT recovers 1.3 kg; at T ≈ 175 ng/dL without RT, subjects lose 0.3 kg. The RT training stimulus accounts for 1.3-2.3 kg LBM gain from near-total androgen suppression to eugonadal levels, with testosterone in the eugonadal range likely modulating the magnitude of the RT hypertrophy response and testosterone suppression still allowing for some level of RT-induced hypertrophy.

3.4. The Female Parallel

A complementary and more nuanced picture emerges from the female literature. Pre-menopausal women have roughly 5-10% of the circulating testosterone levels of eugonadal men yet gain at least comparable relative quantities of lean body mass and strength from RT [53,54]. The most comprehensive direct test in this population is by Alexander et al. [55], a 12-week resistance-training trial in 27 pre-menopausal women that also found no association between total testosterone and lean mass gain, but described two androgen-pathway signals that behave differently. Bioavailable testosterone and the proportion of nuclear-localized androgen receptor were both positively associated with muscle mass and strength. Bioavailable testosterone, alone among the variables measured, also predicted the magnitude of RT-induced hypertrophy, while nuclear-localized androgen receptor localization did not [55]. Additionally, short-term reproductive-hormone fluctuations within the physiological window do not appear to perturb the training adaptation. Nolan et al. performed a multilevel meta-analysis of oral contraceptive use and found no hypertrophic difference between users and non-users [56]. A 2023 umbrella review by Colenso-Semple et al. [57], together with direct muscle-protein-synthesis tests by the same author [58], confirm that menstrual cycle phase influences neither acute strength performance nor MPS. The female evidence thus parallels the male picture: total testosterone within the natural range may be an unhelpful predictor, but bioavailable testosterone may potentially influence the degree of RT-induced hypertrophy adaptations.

4. Discussion

This review pursued three goals. The first was to characterize the dose–response relationship of exogenous testosterone on body composition under controlled GnRH-clamp conditions. Across the dosing ladder this was found to be log-linear, with approximately +1.81 kg of additional lean mass per doubling of weekly dose (14 arms across three trials) and a concurrent pooled fat-mass decline of approximately 1.00 kg per doubling, with no obvious evidence of receptor saturation within the studied range. Expressed in concentration terms, this ladder spanned nadir serum testosterone of roughly 175–250 ng/dL at the lowest dose to roughly 2,400–3,300 ng/dL at the highest (25–600 mg/week; Bhasin et al. 2001 [3] and 2005 [12]). Importantly, the peak testosterone of all of these doses was likely much higher than these values as these samples were collected roughly one week after testosterone administration. 

Our second goal was to characterize the relationship between endogenous baseline testosterone and RT-induced hypertrophy in eugonadal men. A structured narrative synthesis of six cohorts (n = 195) found that no study reported a significant positive association between baseline total testosterone or free testosterone and hypertrophy, and the only two studies that provided effect estimates (Mobley et al. 2018 [4] r = +0.055, 95% CI −0.21 to +0.32, p = 0.69; Haun et al. 2019 [5] r = −0.049, 95% CI −0.43 to +0.34, p = 0.81) suggested the relationships were indistinguishable from zero. The only positive signals in the literature emerged when the predictor shifted from total circulating concentration toward calculated indices of androgen bioavailability: Peltonen et al. 2018 [32] (FAI, p = 0.019) was significant, and Räntilä et al. 2021 [8] and 2023 [9] (averaged T/SHBG) showed a borderline trend. These findings suggest that, where any positive signal exists, it concerns androgen bioavailability rather than circulating testosterone concentrations. SHBG can become elevated due to low energy availability [59,60], potentially lowering FAI and SHBG has also been found to increase with resistance training [61] and age [62]. However, additional research with gold-standard assays on this topic is needed given that the relationship between free testosterone and RT-induced hypertrophy was null in both cohorts that modeled it and the smaller sample sizes across all of these cohorts likely increases the risk of type 1 error. 

Our third goal was to survey what happens when endogenous testosterone is pushed below the eugonadal floor in healthy men engaging in RT. We found that the hypertrophic response is significantly attenuated (-43 to -73%) but not entirely abolished, and the same lower-bound effect is corroborated by the ADT-exercise literature in already-hypogonadal cancer patients. Taken together, these findings are broadly more consistent with a threshold-like pattern than a simple linear gradient across the endogenous range (see Figure 5). Above and within the eugonadal range, exogenous testosterone is graded and powerful. It also bears repeating that exogenous administration abolishes the normal diurnal and pulsatile variation in serum testosterone and maintains more stable testosterone levels that many times are higher than endogenous peaks for the duration of dosing. However, when naturally produced within the eugonadal range, circulating testosterone does not clearly predict the hypertrophic response to a given RT stimulus. Below the eugonadal floor, testosterone becomes permissive: it appears to be required for the hypertrophic transduction system to operate at full capacity, but no additional benefit accrues once the threshold is crossed. 

This framework reconciles much of the confusion around the idea that testosterone levels within the natural range are somehow predictive of hypertrophic potential. One interpretation consistent with the available data is that the testosterone signaling system behaves in a threshold-like manner, being either sufficient or insufficient. When testosterone is sufficient, the determinants of the hypertrophic response potentially lie elsewhere, likely in mechanotransduction, ribosomal biogenesis, satellite cell capacity, motor unit recruitment, and the molecular and morphological variables that contemporary phenotyping work continues to map. The convergent evidence points away from total or free testosterone and potentially even away from androgen receptor density [63], as the rate-limiting variable appears to be translational capacity, as at least one study has found no differences in androgen-receptors between responders and non-responders, with an acute difference in AR DNA-binding activity opposite to the hormone hypothesis, being higher in non-responders [63]. While not the focus of this review, ribosome biogenesis and nucleolar expansion may be a principal bottleneck for chronic hypertrophy [64], complemented by satellite-cell pool expansion [1] and post-transcriptional control via exercise-responsive microRNAs [65].

Figure 5.  Unified saturation/threshold model across the full testosterone range. Three distinct phases are overlaid on a single ΔLBM-versus-testosterone plot. Left (red): Pharmacological suppression and chronic androgen-deprivation cohorts engaged in RT show attenuated but non-zero training responses. Middle (green): The four eugonadal cohorts reporting lean mass in kilograms show no consistent relationship between ΔLBM and total testosterone across the natural physiological range. Right (blue): GnRH-clamp dose-response in the absence of RT shows a Log-linear gain in lean mass with escalating exogenous T.

4.1. Limitations

Due to the exploratory and descriptive nature of the current investigation, several limitations warrant consideration. First, the present review constitutes a structured and partly qualitative narrative synthesis rather than a quantitative meta-analysis on the relationship between endogenous or exogenous testosterone and hypertrophy outcomes. This is largely due to the disparate and incomplete nature of the relevant data, which currently precludes a formal quantitative meta-analysis. Second, the descriptive pooled regression in Figure 1 combines multiple dose arms from the same three parent studies and does not account for arm-level dependence, cohort heterogeneity, or body-composition measurement methodology, which may artificially inflate both precision and confidence. As such, the reported R² should be interpreted as illustrative rather than inferential. In eugonadal men, four of six contributing cohorts entered the synthesis as tier-3 entries (no per-study effect size or correlations in the published article) rather than as quantitative effect sizes, reflecting the field's historical practice of reporting hormone-hypertrophy associations via stepwise regression, principal-component analysis, or extreme-group comparison, rather than full-sample regression. This is, however, a methodological limitation of the underlying literature, not of the present synthesis. Third, great variation in study design was observed. Hypertrophy outcomes were highly heterogeneous across cohorts (fiber CSA, MRI CSA, DXA LBM, ultrasound CSA and muscle thickness), and the present synthesis treats these measurements as exchangeable indices of RT-induced skeletal muscle growth. This assumption is not well supported. In the McCall et al. 1996 [10] cohort, where both indices were obtained in the same arms of the same men, the increase in biceps brachii cross-sectional area was not correlated with the increase in mean fiber area (r = 0.191), type I fiber area (r = 0.197), or type II fiber area (r = 0.353), despite closely similar group-mean increases of 12.7% and 14.5%. Cohorts also differed along several other axes plausibly contributing to heterogeneity: training duration (6–20 weeks), training status (untrained versus previously resistance-trained), session frequency (2–4×/week), volume and loading scheme, exercise selection and the muscle groups sampled (lower-limb musculature in five cohorts and the elbow flexors in one), proximity to failure, and the degree of dietary standardization. Lastly, additional heterogeneity likely arose from differences in testosterone assay methodology (e.g., immunoassay versus LC–MS/MS), blood-sampling timing relative to the diurnal testosterone rhythm, and variation in SHBG and albumin concentrations influencing calculated free or bioavailable testosterone. Such factors may introduce substantial measurement error and attenuate detectable associations between circulating androgens and hypertrophy outcomes.

Given the narrow span, small number of studies, and limited number of extractable continuous effect sizes, formal subgroup or meta-regression analyses were therefore not feasible.  More broadly, relevant data on key biomarkers were limited. In fact, bioavailability indices (FAI; T/SHBG) were measured in only two cohorts with different predictor specifications that could not be pooled. The positive signals from Peltonen et al. [32] and Räntilä et al. [8,9] are therefore reported based only on the directional finding they represent, and warrant replication in adequately powered cohorts. Notably, Peltonen et al. [32] reported a responder (n = 10) versus non-responder (n = 4) subgroup comparison that would likely be attenuated in a continuous full-sample re-analysis if raw data were available. Future work should test the baseline-androgen-bioavailability hypothesis using free testosterone measured by gold-standard equilibrium dialysis or accurately-calculated FAI, analyzed as a continuous predictor across the full sample. They should also control for low energy availability and excessive RT volume, both of which are known to elevate SHBG and thereby reduce free and bioavailable testosterone, potentially confounding any apparent association with the hypertrophic response.  Future work could also investigate the employment of more subtle non-linear or threshold associations within the eugonadal range itself, as well as potential effect modification by factors such as training volume, energy availability, SHBG concentration, or androgen bioavailability. However, these possibilities would require large, standardized cohorts that are adequately powered for continuous modeling approaches and harmonized endocrine measurements. Finally, the synthesis speaks only to the eugonadal range as it appears in young men under research conditions. The endogenous/eugonadal cohorts described are, moreover, almost entirely young men (cohort ages ~18-34 y). Therefore, the lack of association between endogenous testosterone and RT-induced hypertrophy can only be assumed in young adults, as it appears the 40-60-year range (or older) is essentially unstudied. By contrast, the exogenous dose–response studies include older men (e.g., Bhasin et al. 2005), suggesting those results are more broadly applicable.

5. Conclusions

The available human evidence suggests that testosterone exerts distinct effects on hypertrophy responses across different regions of the physiological spectrum. Under GnRH-clamped conditions, exogenous testosterone administration produces a clear dose-dependent increase in lean body mass and a concomitant reduction in fat mass. In contrast, across currently available longitudinal cohorts of eugonadal men undergoing RT, baseline circulating total and free testosterone have not shown a consistent association with the subsequent hypertrophic response.

Evidence from pharmacological suppression studies and androgen-deprivation cohorts further indicates that testosterone likely plays a permissive role below the hypogonadal threshold: RT-induced hypertrophy remains possible under profound androgen suppression but appears to be significantly attenuated. Taken together, the present literature is more consistent with a threshold-like model of endogenous testosterone levels on muscle growth. Neither the acute post-exercise testosterone surge nor chronic differences in baseline testosterone within the normal range appear to produce a greater muscle hypertrophy response from RT. As an approximate guide to the magnitudes involved: i) exogenous testosterone increases lean mass by ~1.8 kg and decreases fat mass by ~1.0 kg per doubling of weekly dose; ii) baseline total testosterone within the eugonadal range shows essentially no relationship with RT-induced lean mass gain; iii) pharmacological suppression to extremely low testosterone concentrations in the 30-45 ng/dL range attenuates the training response by ~43–73%, but resistance training during chronic androgen deprivation still allows for a significant increase in lean mass.

Importantly, the current evidence base remains limited by small cohort sizes, heterogeneous endocrine methodologies, variable hypertrophy endpoints, and incomplete reporting of continuous effect sizes. Future studies should employ standardized androgen assays, rigorous blood-sampling protocols, continuous full-sample modelling approaches and direct assessment of androgen bioavailability to clarify whether subtle context-dependent relationships exist within the eugonadal range.

Author Contributions: Conceptualization – B.T.H.; Methodology - B.H., T.R.W., and A.J.G.; Data curation – B.T.H.; Formal analysis – B.T.H.; Validation – F.C. – Supervision – T.R.W. and A.J.G.; Writing – Original Draft Preparation – B.T.H.; Writing – Review & Editing – B.T.H., T.R.W., F.C., and A.J.G.; Funding acquisition – A.J.G. All authors have read and agreed to the published version of the manuscript.

Funding: This research received no external funding.

Institutional Review Board Statement: Not applicable. This study involved secondary analysis of data from previously published studies and did not include human participants or identifiable personal data.

Informed Consent Statement: Not applicable.

Data Availability Statement: All extracted study-level data underlying the narrative synthesis and dose–response regression are tabulated in Table 1 and Figures 1 and 2, and in the figure captions of Figures 3–5. Source records are maintained in the project bibliography (paper_db.json; cited_papers.json) and available on reasonable request.

Conflicts of Interest: B.T.H., T.R.W., and A.J.G. are all business owners and career writers and content creators in the nutrition, fitness, and health industry. T.R.W is Chief Science Officer of BetterBrain and Headroom Health and a scientific advisor to Hintsa Performance, Somma Labs, NeuroTrainer, Alively, Thriva, and Unbound Health. A.J.G. is a paid scientific advisor to AmpHP Inc and is the co-founder of Vitality Blueprint, BioMolecular Athlete, and Absolute Rest. None of these relationships result in any direct or indirect conflicts with the content or topic of this manuscript.

References

1. Sinha-Hikim, I.; Roth, S.M.; Lee, M.I.; Bhasin, S. Testosterone-induced muscle hypertrophy is associated with an increase in satellite cell number in healthy, young men. American journal of physiology. Endocrinology and metabolism 2003, 285, E197–205, doi:10.1152/ajpendo.00370.2002.

2. Sinha-Hikim, I.; Taylor, W.E.; Gonzalez-Cadavid, N.F.; Zheng, W.; Bhasin, S. Androgen receptor in human skeletal muscle and cultured muscle satellite cells: up-regulation by androgen treatment. J Clin Endocrinol Metab 2004, 89, 5245–5255, doi:10.1210/jc.2004-0084.

3. Bhasin, S.; Woodhouse, L.; Casaburi, R.; Singh, A.B.; Bhasin, D.; Berman, N.; Chen, X.; Yarasheski, K.E.; Magliano, L.; Dzekov, C.; et al. Testosterone dose-response relationships in healthy young men. American journal of physiology. Endocrinology and metabolism 2001, 281, E1172–1181.

4. Mobley, C.B.; Haun, C.T.; Roberson, P.A.; Mumford, P.W.; Kephart, W.C.; Romero, M.A.; Osburn, S.C.; Vann, C.G.; Young, K.C.; Beck, D.T.; et al. Biomarkers associated with low, moderate, and high vastus lateralis muscle hypertrophy following 12 weeks of resistance training. PLoS One 2018, 13, e0195203, doi:10.1371/journal.pone.0195203.

5. Haun, C.T.; Vann, C.G.; Mobley, C.B.; Osburn, S.C.; Mumford, P.W.; Roberson, P.A.; Romero, M.A.; Fox, C.D.; Parry, H.A.; Kavazis, A.N.; et al. Pre-training Skeletal Muscle Fiber Size and Predominant Fiber Type Best Predict Hypertrophic Responses to 6 Weeks of Resistance Training in Previously Trained Young Men. Frontiers in physiology 2019, 10, 297, doi:10.3389/fphys.2019.00297.

6. Morton, R.W.; Oikawa, S.Y.; Wavell, C.G.; Mazara, N.; McGlory, C.; Quadrilatero, J.; Baechler, B.L.; Baker, S.K.; Phillips, S.M. Neither load nor systemic hormones determine resistance training-mediated hypertrophy or strength gains in resistance-trained young men. Journal of applied physiology 2016, 121, 129–138, doi:10.1152/japplphysiol.00154.2016.

7. Morton RW, S.K., Gallaugher MPB, Oikawa SY, McNicholas PD, Fujita S and Phillips SM. Muscle Androgen Receptor Content but Not Systemic Hormones Is Associated With Resistance Training-Induced Skeletal Muscle Hypertrophy in Healthy, Young Men. Front. Physiol. 2018, 9, 1373, doi:10.3389/fphys.2018.01373.

8. Rantila, A.; Ahtiainen, J.P.; Avela, J.; Restuccia, J.; Kidgell, D.; Hakkinen, K. High Responders to Hypertrophic Strength Training Also Tend to Lose More Muscle Mass and Strength During Detraining Than Low Responders. J Strength Cond Res 2021, 35, 1500–1511, doi:10.1519/JSC.0000000000004044.

9. Rantila, A.; Ahtiainen, J.P.; Hakkinen, K. Effects of Acute Loading Induced Fatigability, Acute Serum Hormone Responses and Training Volume to Individual Hypertrophy and Maximal Strength during 10 Weeks of Strength Training. J Sports Sci Med 2023, 22, 559–570, doi:10.52082/jssm.2023.559.

10. McCall, G.E.; Byrnes, W.C.; Dickinson, A.; Pattany, P.M.; Fleck, S.J. Muscle fiber hypertrophy, hyperplasia, and capillary density in college men after resistance training. Journal of applied physiology 1996, 81, 2004–2012, doi:10.1152/jappl.1996.81.5.2004.

11. McCall, G.E.; Byrnes, W.C.; Fleck, S.J.; Dickinson, A.; Kraemer, W.J. Acute and chronic hormonal responses to resistance training designed to promote muscle hypertrophy. Can J Appl Physiol 1999, 24, 96–107.

12. Bhasin, S.; Woodhouse, L.; Casaburi, R.; Singh, A.B.; Mac, R.P.; Lee, M.; Yarasheski, K.E.; Sinha-Hikim, I.; Dzekov, C.; Dzekov, J.; et al. Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on the skeletal muscle. J Clin Endocrinol Metab 2005, 90, 678–688, doi:10.1210/jc.2004-1184.

13. Bhasin, S.; Travison, T.G.; Storer, T.W.; Lakshman, K.; Kaushik, M.; Mazer, N.A.; Ngyuen, A.H.; Davda, M.N.; Jara, H.; Aakil, A.; et al. Effect of testosterone supplementation with and without a dual 5alpha-reductase inhibitor on fat-free mass in men with suppressed testosterone production: a randomized controlled trial. JAMA 2012, 307, 931–939, doi:10.1001/jama.2012.227.

14. Bhasin, S.; Storer, T.W.; Berman, N.; Callegari, C.; Clevenger, B.; Phillips, J.; Bunnell, T.J.; Tricker, R.; Shirazi, A.; Casaburi, R. The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. The New England journal of medicine 1996, 335, 1–7, doi:10.1056/NEJM199607043350101.

15. Pastuszak, A.W.; Gittelman, M.; Tursi, J.P.; Jaffe, J.S.; Schofield, D.; Miner, M.M. Pharmacokinetics of testosterone therapies in relation to diurnal variation of serum testosterone levels as men age. Andrology 2022, 10, 209–222, doi:10.1111/andr.13108.

16. Yu, J.G.; Bonnerud, P.; Eriksson, A.; Stal, P.S.; Tegner, Y.; Malm, C. Effects of long term supplementation of anabolic androgen steroids on human skeletal muscle. PLoS One 2014, 9, e105330, doi:10.1371/journal.pone.0105330.

17. Bonnecaze, A.K.; O'Connor, T.; Aloi, J.A. Characteristics and Attitudes of Men Using Anabolic Androgenic Steroids (AAS): A Survey of 2385 Men. Am J Mens Health 2020, 14, 1557988320966536, doi:10.1177/1557988320966536.

18. Parkinson, A.B.; Evans, N.A. Anabolic androgenic steroids: a survey of 500 users. Med Sci Sports Exerc 2006, 38, 644–651, doi:10.1249/01.mss.0000210194.56834.5d.

19. Wang, C.; Cunningham, G.; Dobs, A.; Iranmanesh, A.; Matsumoto, A.M.; Snyder, P.J.; Weber, T.; Berman, N.; Hull, L.; Swerdloff, R.S. Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J Clin Endocrinol Metab 2004, 89, 2085–2098, doi:10.1210/jc.2003-032006.

20. West, D.W.; Burd, N.A.; Tang, J.E.; Moore, D.R.; Staples, A.W.; Holwerda, A.M.; Baker, S.K.; Phillips, S.M. Elevations in ostensibly anabolic hormones with resistance exercise enhance neither training-induced muscle hypertrophy nor strength of the elbow flexors. Journal of applied physiology 2010, 108, 60–67, doi:10.1152/japplphysiol.01147.2009.

21. West, D.W.; Phillips, S.M. Associations of exercise-induced hormone profiles and gains in strength and hypertrophy in a large cohort after weight training. European journal of applied physiology 2012, 112, 2693–2702, doi:10.1007/s00421-011-2246-z.

22. Mitchell, C.J.; Churchward-Venne, T.A.; Bellamy, L.; Parise, G.; Baker, S.K.; Phillips, S.M. Muscular and systemic correlates of resistance training-induced muscle hypertrophy. PLoS One 2013, 8, e78636, doi:10.1371/journal.pone.0078636.

23. McCaulley, G.; McBride, J.; Cormie, P.; Hudson, M.; Nuzzo, J.; Quindry, J.; Triplett, N. Acute hormonal and neuromuscular responses to hypertrophy, strength and power type resistane exercise. European journal of applied physiology 2009, 105, 695–704, doi:10.1007/s00421-008-0951-z.

24. Tu, Q.; Li, G.; Wang, S. Effect of acute exercise on the dynamics of testosterone levels: a systematic review of randomized controlled trials. PeerJ 2026, 14, e20615, doi:10.7717/peerj.20615.

25. Walker, S.; Häkkinen, K.; Newton, R.; Markworth, J.; Pundir, S.; Haff, G.; Cameron-Smith, D.; Blazevich, A. Acute responses of comprehensive gonadosteroids and corticosteroids to resistance exercise before and after 10Â weeks of supervised strength training. Experimental Physiology 2019, 105, doi:10.1113/EP087995.

26. Ratamess, N. Effects of Heavy Resistance Exercise Volume on Post-Exercise Androgen Receptor Content in Resistance-Trained Men. ETD Collection for University of Connecticut 2004, 36, doi:10.1249/00005768-200405001-01138.

27. Kraemer, R.R.; Kilgore, J.L.; Kraemer, G.R.; Castracane, V.D. Growth hormone, IGF-I, and testosterone responses to resistive exercise. Med Sci Sports Exerc 1992, 24, 1346–1352.

28. Raastad, T.; Bjoro, T.; Hallen, J. Hormonal responses to high- and moderate-intensity strength exercise. European journal of applied physiology 2000, 82, 121–128, doi:10.1007/s004210050661.

29. Diver, M.J.; Imtiaz, K.E.; Ahmad, A.M.; Vora, J.P.; Fraser, W.D. Diurnal rhythms of serum total, free and bioavailable testosterone and of SHBG in middle-aged men compared with those in young men. Clinical endocrinology 2003, 58, 710–717, doi:10.1046/j.1365-2265.2003.01772.x.

30. Brambilla, D.J.; O'Donnell, A.B.; Matsumoto, A.M.; McKinlay, J.B. Intraindividual variation in levels of serum testosterone and other reproductive and adrenal hormones in men. Clinical endocrinology 2007, 67, 853–862, doi:10.1111/j.1365-2265.2007.02976.x.

31. D'Andrea, S.; Spaggiari, G.; Barbonetti, A.; Santi, D. Endogenous transient doping: physical exercise acutely increases testosterone levels-results from a meta-analysis. J Endocrinol Invest 2020, 43, 1349–1371, doi:10.1007/s40618-020-01251-3.

32. Peltonen, H.; Walker, S.; Hackney, A.C.; Avela, J.; Hakkinen, K. Increased rate of force development during periodized maximum strength and power training is highly individual. European journal of applied physiology 2018, 118, 1033–1042, doi:10.1007/s00421-018-3836-9.

33. Kvorning, T.; Andersen, M.; Brixen, K.; Madsen, K. Suppression of endogenous testosterone production attenuates the response to strength training: a randomized, placebo-controlled, and blinded intervention study. American journal of physiology. Endocrinology and metabolism 2006, 291, E1325–1332, doi:10.1152/ajpendo.00143.2006.

34. Kvorning, T.; Andersen, M.; Brixen, K.; Schjerling, P.; Suetta, C.; Madsen, K. Suppression of testosterone does not blunt mRNA expression of myoD, myogenin, IGF, myostatin or androgen receptor post strength training in humans. J Physiol 2007, 578, 579–593, doi:10.1113/jphysiol.2006.122671.

35. Gharahdaghi, N.; Rudrappa, S.; Brook, M.S.; Farrash, W.; Idris, I.; Aziz, M.H.A.; Kadi, F.; Papaioannou, K.; Phillips, B.E.; Sian, T.; et al. Pharmacological hypogonadism impairs molecular transducers of exercise-induced muscle growth in humans. J Cachexia Sarcopenia Muscle 2022, 13, 1134–1150, doi:10.1002/jcsm.12843.

36. Longland, T.M.; Oikawa, S.Y.; Mitchell, C.J.; Devries, M.C.; Phillips, S.M. Higher compared with lower dietary protein during an energy deficit combined with intense exercise promotes greater lean mass gain and fat mass loss: a randomized trial. Am J Clin Nutr 2016, 103, 738–746, doi:10.3945/ajcn.115.119339.

37. Mauras, N.; Hayes, V.; Welch, S.; Rini, A.; Helgeson, K.; Dokler, M.; Veldhuis, J.D.; Urban, R.J. Testosterone deficiency in young men: marked alterations in whole body protein kinetics, strength, and adiposity. J Clin Endocrinol Metab 1998, 83, 1886–1892, doi:10.1210/jcem.83.6.4892.

38. Finkelstein, J.S.; Lee, H.; Burnett-Bowie, S.A.; Pallais, J.C.; Yu, E.W.; Borges, L.F.; Jones, B.F.; Barry, C.V.; Wulczyn, K.E.; Thomas, B.J.; et al. Gonadal steroids and body composition, strength, and sexual function in men. The New England journal of medicine 2013, 369, 1011–1022, doi:10.1056/NEJMoa1206168.

39. Shao, W.; Zhang, H.; Qi, H.; Zhang, Y. The effects of exercise on body composition of prostate cancer patients receiving androgen deprivation therapy: An update systematic review and meta-analysis. PLoS One 2022, 17, e0263918, doi:10.1371/journal.pone.0263918.

40. Segal, R.J.; Reid, R.D.; Courneya, K.S.; Malone, S.C.; Parliament, M.B.; Scott, C.G.; Venner, P.M.; Quinney, H.A.; Jones, L.W.; D'Angelo, M.E.; et al. Resistance exercise in men receiving androgen deprivation therapy for prostate cancer. J Clin Oncol 2003, 21, 1653–1659, doi:10.1200/JCO.2003.09.534.

41. Houben, L.H.P.; Overkamp, M.; P, V.A.N.K.; Trommelen, J.; JGH, V.A.N.R.; P, D.E.V.; K, D.E.L.; S, V.D.M.; Mikkelsen, U.R.; Verdijk, L.B.; et al. Resistance Exercise Training Increases Muscle Mass and Strength in Prostate Cancer Patients on Androgen Deprivation Therapy. Med Sci Sports Exerc 2023, 55, 614–624, doi:10.1249/MSS.0000000000003095.

42. Cormie, P.; Galvao, D.A.; Spry, N.; Joseph, D.; Chee, R.; Taaffe, D.R.; Chambers, S.K.; Newton, R.U. Can supervised exercise prevent treatment toxicity in patients with prostate cancer initiating androgen-deprivation therapy: a randomised controlled trial. BJU Int 2015, 115, 256–266, doi:10.1111/bju.12646.

43. Galvao, D.A.; Taaffe, D.R.; Spry, N.; Joseph, D.; Newton, R.U. Combined resistance and aerobic exercise program reverses muscle loss in men undergoing androgen suppression therapy for prostate cancer without bone metastases: a randomized controlled trial. J Clin Oncol 2010, 28, 340–347, doi:10.1200/JCO.2009.23.2488.

44. Benito, P.J.; Cupeiro, R.; Ramos-Campo, D.J.; Alcaraz, P.E.; Rubio-Arias, J.A. A Systematic Review with Meta-Analysis of the Effect of Resistance Training on Whole-Body Muscle Growth in Healthy Adult Males. Int J Environ Res Public Health 2020, 17, doi:10.3390/ijerph17041285.

45. Tian, S.; Ding, M.; Sun, H. The effects of resistance exercise on body composition and physical function in prostate cancer patients undergoing androgen deprivation therapy: an update systematic review and meta-analysis. The aging male : the official journal of the International Society for the Study of the Aging Male 2022, 25, 281–292, doi:10.1080/13685538.2022.2146670.

46. Lopez, P.; Newton, R.U.; Taaffe, D.R.; Winters-Stone, K.; Galvao, D.A.; Buffart, L.M. Moderators of resistance-based exercise programs' effect on sarcopenia-related measures in men with prostate cancer previously or currently undergoing androgen deprivation therapy: An individual patient data meta-analysis. J Geriatr Oncol 2023, 14, 101535, doi:10.1016/j.jgo.2023.101535.

47. Bhasin, S.; Brito, J.P.; Cunningham, G.R.; Hayes, F.J.; Hodis, H.N.; Matsumoto, A.M.; Snyder, P.J.; Swerdloff, R.S.; Wu, F.C.; Yialamas, M.A. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2018, 103, 1715–1744, doi:10.1210/jc.2018-00229.

48. De Naeyer, H.; Bogaert, V.; De Spaey, A.; Roef, G.; Vandewalle, S.; Derave, W.; Taes, Y.; Kaufman, J.M. Genetic variations in the androgen receptor are associated with steroid concentrations and anthropometrics but not with muscle mass in healthy young men. PLoS One 2014, 9, e86235, doi:10.1371/journal.pone.0086235.

49. Qin, H.; Jiao, W.; Liao, G. The Association of Low Muscle Mass With Serum Sex Hormones and Sex Hormone-Binding Globulin. J Cachexia Sarcopenia Muscle 2025, 16, e70056, doi:10.1002/jcsm.70056.

50. Gates, M.A.; Mekary, R.A.; Chiu, G.R.; Ding, E.L.; Wittert, G.A.; Araujo, A.B. Sex steroid hormone levels and body composition in men. J Clin Endocrinol Metab 2013, 98, 2442–2450, doi:10.1210/jc.2012-2582.

51. Eriksson, J.; Haring, R.; Grarup, N.; Vandenput, L.; Wallaschofski, H.; Lorentzen, E.; Hansen, T.; Mellstrom, D.; Pedersen, O.; Nauck, M.; et al. Causal relationship between obesity and serum testosterone status in men: A bi-directional mendelian randomization analysis. PLoS One 2017, 12, e0176277, doi:10.1371/journal.pone.0176277.

52. Grossmann, M. Hypogonadism and male obesity: Focus on unresolved questions. Clinical endocrinology 2018, 89, 11–21, doi:10.1111/cen.13723.

53. Refalo, M.C.; Nuckols, G.; Galpin, A.J.; Gallagher, I.J.; Hamilton, D.L.; Fyfe, J.J. Sex differences in absolute and relative changes in muscle size following resistance training in healthy adults: a systematic review with Bayesian meta-analysis. PeerJ 2025, 13, e19042, doi:10.7717/peerj.19042.

54. Roberts, B.M.; Nuckols, G.; Krieger, J.W. Sex Differences in Resistance Training: A Systematic Review and Meta-Analysis. J Strength Cond Res 2020, 34, 1448–1460, doi:10.1519/JSC.0000000000003521.

55. Alexander, S.E.; Gatto, B.; Knowles, O.E.; Williams, R.M.; Fiebig, K.N.; Jansons, P.; Della Gatta, P.A.; Garnham, A.; Eynon, N.; Wadley, G.D.; et al. Bioavailable testosterone and androgen receptor activation, but not total testosterone, are associated with muscle mass and strength in females. J Physiol 2025, 603, 5181–5208, doi:10.1113/JP286803.

56. Nolan, D.; McNulty, K.L.; Manninen, M.; Egan, B. The Effect of Hormonal Contraceptive Use on Skeletal Muscle Hypertrophy, Power and Strength Adaptations to Resistance Exercise Training: A Systematic Review and Multilevel Meta-analysis. Sports medicine 2024, 54, 105–125, doi:10.1007/s40279-023-01911-3.

57. Colenso-Semple, L.M.; D'Souza, A.C.; Elliott-Sale, K.J.; Phillips, S.M. Current evidence shows no influence of women's menstrual cycle phase on acute strength performance or adaptations to resistance exercise training. Front Sports Act Living 2023, 5, 1054542, doi:10.3389/fspor.2023.1054542.

58. Colenso-Semple, L.M.; McKendry, J.; Lim, C.; Atherton, P.J.; Wilkinson, D.J.; Smith, K.; Phillips, S.M. Menstrual cycle phase does not influence muscle protein synthesis or whole-body myofibrillar proteolysis in response to resistance exercise. J Physiol 2025, 603, 1109–1121, doi:10.1113/JP287342.

59. Isola, V.; Hulmi, J.J.; Mbay, T.; Kyrolainen, H.; Hakkinen, K.; Ahola, V.; Helms, E.R.; Ahtiainen, J.P. Changes in hormonal profiles during competition preparation in physique athletes. European journal of applied physiology 2024, doi:10.1007/s00421-024-05606-z.

60. Hennigar, S.R.; Berryman, C.E.; Harris, M.N.; Karl, J.P.; Lieberman, H.R.; McClung, J.P.; Rood, J.C.; Pasiakos, S.M. Testosterone Administration During Energy Deficit Suppresses Hepcidin and Increases Iron Availability for Erythropoiesis. J Clin Endocrinol Metab 2020, 105, doi:10.1210/clinem/dgz316.

61. Roberts, C.K.; Croymans, D.M.; Aziz, N.; Butch, A.W.; Lee, C.C. Resistance training increases SHBG in overweight/obese, young men. Metabolism: clinical and experimental 2013, 62, 725–733, doi:10.1016/j.metabol.2012.12.004.

62. Xu, P.; Zeng, R.; Wan, Q.; Xie, Y.; Liu, X.; An, S.; Jiang, J.; Yang, J.; Zhou, Y.; Shen, X. Aging-related increases in serum sex hormone-binding globulin levels in men might be related to increased synthesis. Exp Gerontol 2023, 179, 112249, doi:10.1016/j.exger.2023.112249.

63. Bergamasco, J.G.A.; Scarpelli, M.C.; Godwin, J.S.; Mesquita, P.H.C.; Chaves, T.S.; da Silva, D.G.; Bittencourt, D.; Dias, N.F.; Medalha, R.A., Jr.; Carello Filho, P.C.; et al. Androgen receptor markers do not differ between nonresponders and responders to resistance training-induced muscle hypertrophy. Journal of applied physiology 2024, 137, 910–918, doi:10.1152/japplphysiol.00354.2024.

64. Munoz Lopez, M.; Lopez-Gil, J.F.; Ramirez de la Piscina Viudez, X.; Baz-Valle, E.; Tornero Aguilera, J.F. Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators. Cells 2026, 15, doi:10.3390/cells15111041.

65. Ozdemir, K.; Demir, Y. Exercise-induced microRNAs: molecular pathways and adaptive remodeling of skeletal muscle. Pflugers Arch 2026, 478, doi:10.1007/s00424-026-03177-w.