Hormones, Hypertrophy, and Hype: An Evidence-Guided Primer on Endogenous Endocrine Influences on Exercise-Induced Muscle Hypertrophy

An evidence-guided primer on endocrine influences on exercise-induced muscle hypertrophy.

Abstract

We review the evidence indicating that endogenous changes in these hormones, including testosterone, growth hormone, insulin growth factor-1, and estrogen, and their proposed anabolic effects contribute to and augment resistance exercise training (RET)-induced hypertrophy. Additionally, we provide recommendations for gold-standard methodological rigor to establish best practices for verifying menstrual phases as part of their research, ultimately enhancing our understanding of the impact of ovarian hormones on RET-induced adaptations.

KEY POINTS

• The acute postexercise rise in systemic “anabolic hormones” does not play a major role in stimulating muscle protein synthesis, leading to hypertrophy.

• In a relative comparison, males and females respond similarly to resistance exercise training regarding strength and hypertrophy.

• The evidence currently available does not support females periodize their resistance exercise training (RET) practices (or exercise) to fit a certain phase of their menstrual cycle to promote

• Adaptations or “take advantage” of hormonal concentrations.

• Menstrual cycle symptoms — cramps, pain, bloating, and psychological-based — need to be acknowledged as others have found these symptoms to impact training. These symptoms should be an important consideration when programming females’ training practices but are not indicative of physiological benefit or detriment. If athletes do not have these symptoms, there is little point in varying RET-related or other training practices.

• The menstrual cycle is characterized by extraordinary variation: researchers need to employ gold-standard practices to establish phases if this is an important part of their research question or if they aim to make menstrual cycle phase-related conclusions/recommendations.

INTRODUCTION

The regulation of human adult skeletal muscle mass involves multiple variables, which can be categorized as either external (variables within our control) or internal (inherent biological factors) system variables (1). Progressive resistance exercise training (RET) stands out as the most potent nonpharmacological stimulus for increasing skeletal muscle mass (2). Skeletal muscle hypertrophy, defined as an increase in the axial cross-sectional area of a muscle/muscle fiber, is assessed through various methods such as magnetic resonance imaging (MRI), computed tomography, ultrasound, or biopsies examining muscle fiber cross-sectional area (3). RET-induced skeletal muscle hypertrophy results from a complex and incompletely understood interplay between external variables (e.g., RET variable programming, diet, and sleep) and internal variables (e.g., mechanotransduction, ribosomes, gene expression, including epigenetic modification, satellite cell activity); for more information, readers are referred to these recent reviews (1,4). Despite substantial research focusing on how external variables affect RET-induced skeletal muscle hypertrophy, we propose that the key variables affecting the hypertrophic response depend on an individual’s internal variables and their interaction with external variables (1,4). Muscle hypertrophy occurs when there are chronic periods of positive net protein balance, defined as when the rate of muscle protein synthesis exceeds that of muscle protein breakdown. Although RET stimulates increases in both muscle protein synthesis and breakdown, synthesis is stimulated to a greater extent, promoting muscle protein accrual and eventual hypertrophy (3).

One thesis suggests that both acute (minutes, hours) and chronic (days, weeks, months) fluctuations within the normal physiological range of systemic “anabolic” hormones, including testosterone, growth hormone, and insulin-like growth factor-1 (IGF-1), serve as important internal stimuli that contribute causally to RET-induced skeletal muscle hypertrophy (5). This hormonally driven hypertrophy thesis stems largely from research proposing that acute postexercise elevations of testosterone, growth hormone, or IGF-1 played significant roles in promoting anabolism and were, at least partially, responsible for RET-induced adaptations (6–11). However, multiple studies, including male and female humans, have demonstrated that acute postexercise endocrine responses (minutes to hours) are not necessary for hypertrophy to occur (12–17). Acute increases in anabolic hormones neither enhance muscle protein synthesis nor contribute to muscle hypertrophy with RET. Importantly, acute rises in anabolic hormones and muscle anabolic signaling are also unrelated to longer-term RET-induced skeletal muscle hypertrophic adaptations (12–17).

Moreover, aside from experimental scenarios aimed at assessing the role of anabolic hormones (sex steroids) in RET-induced hypertrophy (12–17), a naturally occurring model for examining the influence of testosterone on hypertrophy involves comparing RET-induced adaptations between males and females. It has been hypothesized that biological sex may influence varied hypertrophic adaptations and that sexual dimorphism is largely influenced by hormonal variances (18). Notably, females have 10–20- and 200-fold lower systemic total and free testosterone concentrations, respectively, following puberty compared to males (19). Due to testosterone’s anabolic effect, it has been inferred that females have less “potential” to increase their muscle mass than males (19); however, research has shown that females achieve the same relative increases in muscle mass and strength gain following RET compared to males (20). This meta-analytic observation (20), recently updated (21), is further supported by mechanistic data showing no sex-based differences between the aggregate responses of muscle protein synthesis acutely (in the immediate 3 h postexercise) and over the ensuing 24 h following resistance exercise when males and females are compared (12). It has been speculated that an increase in estrogen concentration may partially counter the lower testosterone concentration in females (22,23). However, because the same relative changes in muscle are possible between men and women over a long-term (weeks–months) resistance training protocol (20), the acute fluctuations in estrogen and testosterone, despite being substantially different between males and females, are moot in terms of the ultimate phenotype (20,21).

The proposed anabolic effects of estrogen are supported by research on hormone replacement therapy (HRT), where HRT has been shown to counteract the upregulation of the ubiquitin–proteasome system in postmenopausal females (24). Furthermore, estrogen has been linked to myogenic gene expression following RET, suggesting its potential involvement in enhancing sensitivity to anabolic stimuli (25). Animal models of complete ovariectomy are also often cited as evidence for estrogen’s role in preserving muscle mass in humans (26). However, despite these proposed effects, females undergoing HRT do not exhibit meaningful differences compared to their untreated counterparts in terms of lean mass (27–29). For instance, Sites et al. (29) conducted a 2-yr study involving 76 postmenopausal females who were randomized to receive either conjugated estrogens plus medroxygenprogesterone acetate or a placebo daily. The authors reported that HRT did not affect body composition, including fat-free mass (29). Alternatively, Chen and colleagues (28) examined 835 females (mean age = 63.1 yr) who were approximately 14 yr postmenopause. They underwent 3 yr of estrogen plus progestin therapy or received placebo treatment. The authors concluded that estrogen plus progestin administration significantly reduced the loss of lean soft tissue mass compared to placebo (−0.04 vs -0.44 kg; P = 0.001). However, it is important to note that lean mass represents the aggregate sum of any fat- and bone-free mass and may not fully reflect muscle mass. Although this preservation was statistically significant, the magnitude (~400 g) falls within repeat-scan error for dual x-ray absorptiometry in reporting lean mass (30–32), leaving its functional (i.e., performance) significance unclear.

Furthermore, it has been suggested that females could optimize their RET programming by periodizing it according to the hormonal fluctuations of estrogen and progesterone across their menstrual cycle, potentially promoting greater adaptations (33,34). However, current evidence indicates that menstrual cycle phase does not influence acute strength performance or RET-induced hypertrophic adaptations (26). Although research on whether females should periodize their RET programming to account for their hormonal fluctuations is limited, existing literature is conflicting with some reviews supporting the influence of estrogen or progesterone on anabolic processes in humans and others refuting it (19,26,35,36). Given the substantial variability in menstrual cycle length, ovulation occurrence, and hormone concentrations within and between individuals (19), employing gold-standard practices (37) to establish menstrual cycle phases (i.e., follicular and luteal) is crucial for future research investigating the effects of the menstrual cycle on exercise training; this is addressed in greater detail below.

This review focuses on the potential effects of endogenous changes in the primary sex hormones testosterone, estrogen, and progesterone and whether these hormones have a role in RET-induced hypertrophy. We highlight research demonstrating that acute (minutes and hours after exercise) rises in endogenous anabolic hormones do not significantly stimulate muscle protein synthesis, promote increases in lean mass (a proxy for muscle mass; for a review, see (38)), or affect increases in strength. Additionally, we examine how periodizing exercise across the menstrual cycle phases does not affect RET-stimulated muscle hypertrophy.

It is important to note that, although there are overlaps between sex hormones and androgens (i.e., testosterone, estrogen), not all “growth-promoting” hormones (e.g., growth hormone, IGF-1) are sex hormones. Furthermore, the conditions discussed in this review pertain to males and premenopausal females who are not pregnant. Notably, we highlight responses to endogenous hormones and not exogenously administered hormones, especially androgenic steroids, of which supraphysiological (well beyond normal diurnal variation) doses are markedly anabolic and hypertrophy-promoting (39).

Lastly, we address a substantial gap in female menstrual cycle–based research, which is the extraordinary variability in the menstrual cycle. Although the menstrual cycle serves as a naturally occurring model to investigate the effects of ovarian hormones, overlooking the inherent variability of the menstrual cycle can lead researchers to an inaccurate understanding of its impact. Therefore, we address current recommendations for researchers to adopt gold-standard methodological rigor in establishing accurate menstrual phases as part of their research questions. It is worth noting that in this review, we will discuss research pertaining to biological sex, which refers to biological differences between females and males, including chromosomes, sex organs, and endogenous sex hormone profiles (40) herein referred to as male/female.

THE ANDROGENICITY OF SEX HORMONES AND SKELETAL MUSCLE ANABOLISM

Androgens exert downstream genomic effects on skeletal muscle by binding to androgen receptors localized within the sarcoplasm (4). Following activation via ligand binding, androgen receptors undergo nuclear translocation and bind to DNA, acting as transcription factors and altering the mRNA expression of thousands of genes (4).

Testosterone is the primary androgen and has both androgenic and anabolic effects (39). In males, over 95% of testosterone is synthesized in the Leydig cells of the testes, whereas in females, testosterone is produced primarily by the conversion of precursor hormones in the adrenal cortex in addition to the ovaries (41). Healthy males produce ~4 to 9 mg of testosterone daily, giving rise to systemic (total) concentrations of 290–1000 ng·dL⁻¹ (10–35 nM) compared to females with systemic concentrations of 14–65 ng·dL⁻¹ (0.5–2.5 nM) (41). There are also mini puberty periods in the first 6 months of life, the true function of which is unknown but involves the activation of the hypothalamic–pituitary–growth axis that promotes early maturation of sexual organs and forms a platform for future fertility (42).

Androgens fulfill various ergogenic, anabolic, and anticatabolic functions, leading to dose-dependent increases in muscular strength, power, endurance, and hypertrophy (41). The significant disparity in testosterone concentration between the sexes emerges predominantly during puberty (43), driving a lasting distinction in muscle characteristics, including muscle fiber size and possibly fiber number, which contributes to greater muscle size among males (44). A persistent decline in testosterone is associated with reduced muscle mass and function (45). Thus, androgens are commonly used as drugs for manipulating muscle mass (45), and the supraphysiological concentration of testosterone-mimicking synthetic androgenic steroids promotes significant skeletal muscle mass increases in both males and females (41).

For illustrative purposes, we have plotted the normal ranges of various hormones proposed to have anabolic effects, indicating both their normal and supraphysiological concentration (resulting from exogenous administration or pathology-induced conditions; Fig. 1). Models investigating the influence of hormones at supraphysiological concentrations allow for deeper insight into the mechanistic pathways of these hormones. However, understanding realities of these ranges, normal and supraphysiological, is crucial for accurately interpreting their potential impact on the body.

Figure 1.

Somatic hormonal profiling panel depicting the concentrations of various proposed anabolic hormones among various physiological and supraphysiological states (39,46–51). From left to right: (A) testosterone, (B) growth hormone, (C) estradiol. GHD, growth hormone deficiency; HA PCOS, hyperandrogenic polycystic ovarian syndrome. This figure was created using BioRender.com.

It is important to acknowledge that testosterone may play a role in the response and adaptations to RET through nongenomic and intracrinologic mechanisms (52). Unlike the genomic responses that involve interaction with DNA prior to translation, testosterone can exert its effects via intracellular signaling molecules, such as protein kinase A, protein kinase C, phospholipase C, phosphoinositide-3 kinase, and mitogen-activated protein kinase, leading to rapid biological responses (52). These nongenomic effects may include activating key mechanisms for hypertrophy, such as increases in transcription, translation, structural proteins, and signaling enzymes (52), though this remains speculative. Another potential role of testosterone in RET adaptations is intracrinological, wherein testosterone may act on skeletal muscle in an intracrine manner, meaning it is synthesized within and acts within the same tissue. The proposed intracrine mechanism involves local intramuscular testosterone precursors, like dihydrotestosterone, dehydroepiandrosterone, progesterone, and androstenedione (Fig. 2), being converted to testosterone in the muscle without the need to enter circulation (52). We also note that there may be mechanistic sex-based differences in how muscles respond to exercise-induced muscle damage in males but not females, being related to the nuclear localization of the androgen receptor (AR) (53). Hatt and colleagues report that eccentric damage increased nuclear-associated AR (nAR) content in males and not females. The authors concluded, “…that AR content but more importantly, nuclear localization, is a factor that differentiates RET-induced hypertrophy between males and females.” (53) Further investigation is needed to elucidate the role of nongenomic and intracrinologic mechanisms of testosterone as well as sex-based differences in the mechanisms that lead to hypertrophy, (54) but ultimately culminate in similar relative muscle gains (20,21).

Figure 2.

A schematic diagram of the compounds, enzymes, and locations of the human steroidogenesis pathways. The red rectangle highlights hormones of interest. [Adapted from Häggström M, Richfield D. Diagram of the pathways of human steroidogenesis. WikiJournal of Medicine 2014:1(1). doi:10.15347/wjm/2014.005. https://en.wikiversity.org/wiki/WikiJournal_of_Medicine/Diagram_of_the_pathways_of_human_steroidogenesis.]

Androgens play a crucial role in the synthesis of estrogen, which is particularly important for female reproductive function (45). Testosterone is the main substrate for estrogen synthesis, a process that is not reversible (45) (Fig. 2). Although the anabolic effects of endogenous testosterone are well known and apparent at puberty (43), our understanding of the ovarian hormones and their influence on muscle mass regulation is limited (55).

Although estrogen’s anabolic effects have garnered some attention, we know very little about the mechanisms of progesterone and its mode of action. The anticatabolic effects of estrogen have some support from research in postmenopausal females undergoing HRT. Postmenopausal females often experience accelerated muscle loss from increased protein breakdown rates, possibly due to decreased estrogen production (56). Estrogen in HRT models has been shown to counteract the upregulation of the ubiquitin–proteasome system, thus reducing protein degradation (24). Moreover, research suggests that estrogen is involved in the signaling and processes influencing RET-induced adaptations, including modulating myogenic gene expression, protein turnover, myosin function, and satellite cell activity, ultimately supporting its anabolic potential (18,27–29). However, none of these studies directly measured hypertrophy or changes in muscle mass.

Regrettably, mechanistically, let alone physiologically, the role of progesterone remains to be elucidated, including whether receptors for progesterone exist in skeletal muscle (26). However, there have been proposals (26) that progesterone can antagonize estrogen’s effects by competing for receptors and blocking the action of estrogen (Fig. 3).

Figure 3.

A. Mechanistic actions of estrogen. B. Hypothesized mechanistic action of progesterone in antagonizing estrogen action. The red X’s indicate points where progesterone is theorized to inhibit estrogen’s action. Specifically, progesterone is hypothesized to block estrogen binding to its receptor, inhibit receptor dimerization, and prevent the activation of estrogen target genes, ultimately inhibiting muscle protein synthesis. Additionally, progesterone is thought to block estrogen binding to GPER, thereby inhibiting GPER-mediated nongenomic signaling. GPER, G-protein coupled estrogen receptor; MPB, muscle protein breakdown; MPS, muscle protein synthesis. This figure was created using BioRender.com.

ACUTE HORMONAL RISES DO NOT AFFECT PROTEIN TURNOVER, SIGNALING, OR HYPERTROPHY IN MALES OR FEMALES

It has been suggested that acute postexercise elevations of circulating anabolic hormones (e.g., testosterone, growth-hormone, IGF-1) are significant contributors to RET-induced adaptations (6–11); however, compelling human studies have demonstrated that these acute postexercise endocrine responses to RET are unrelated to acute anabolic signaling and increments in protein synthesis as well as long-term hypertrophic adaptations (12–16).

To gain deeper insight into the role of an acute increase in anabolic hormones, Wilkinson et al. (14) employed a unilateral RET model with 10 young male participants training thrice weekly for 8 wk. Despite no changes in systemic hormone (free and total testosterone, growth hormone, IGF-1, cortisol) concentrations following acute exercise before and after training, there were significant training-induced increases in type IIx (22 ± 3%; P < 0.05) and IIa muscle fiber cross-sectional area (13% ± 2%; P < 0.001), with no changes observed in the untrained leg (all P > 0.05). In addition, the authors reported a significant strength increase in the trained leg for one repetition maximum leg press (141 ± 26 kg Pre vs 166 ± 25 kg Post) and knee extension (47 ± 7 kg Pre vs 68 ± 12 kg Post) with no changes in the untrained leg. The authors concluded that RET-induced muscle hypertrophy is confined to the limb exercised and does not require changes in systemic hormones (14). Subsequent research from West and colleagues (15) aimed to determine whether the RET-induced elevation of testosterone, growth hormone, and IGF-1 augmented postexercise rates of myofibrillar protein synthesis and phosphorylation of critical signaling proteins involved in mRNA translation. Researchers had eight young males complete two bouts of unilateral RET for the elbow flexors designed to maintain basal hormone concentrations or to elicit an increase in endogenous hormones (high hormone, or HH). The authors observed no difference in rates of muscle protein synthesis in the biceps despite elevated concentrations of testosterone, growth hormone, and IGF-1. In addition, there was a significant increase in the phosphorylation of 70 kDa S6 protein kinase (p70S6K) with no difference between conditions, leading the authors to conclude that the acute increase in systemic hormones does not enhance fed-state anabolic signaling or muscle protein synthesis following resistance exercise (15).

A subsequent investigation had male participants unilaterally train one arm under either the HH or basal hormone milieu for 15 wk (16). Within 15–30 MIN postexercise, the basal hormone condition showed minimal elevations in serum growth hormone, IGF-1, and testosterone compared to the HH condition. The hormonal response with the basal hormonal and HH protocols was similar pretraining to posttraining, suggesting that the hormonal response was maintained chronically throughout the training intervention. The authors reported significant increases in muscle cross-sectional area of 12% in basal hormonal condition compared to 10% in HH, with no statistically significant differences between conditions. In addition, strength increased in both arms, but no difference between conditions was observed (16). The authors concluded that exposure of loaded muscle to acute exercise-induced elevations in endogenous anabolic hormones does not enhance muscle hypertrophy or strength with RET in young males (16).

West and Phillips (17) also investigated associations between acute RET-induced hormonal responses and adaptations to RET among a larger cohort (n = 56) of young males. Acute postexercise serum growth hormone, free testosterone, IGF-1, and cortisol were measured following a high-volume bout of leg exercise at the midpoint of a 12-wk RET study. There were no significant correlations between the exercise-induced elevations (area under the curve (AUC)) of growth hormone, free testosterone, and IGF-1 with gains in lean body mass or leg press strength, showing that acute postexercise hormonal increases are uncorrelated with RET-induced hypertrophic or strength adaptations (17).

As lower testosterone concentration has been posited to attenuate RET-induced adaptations in females, West and colleagues (12) performed a sex-based comparison of rates of muscle protein synthesis and anabolic signaling following high-intensity resistance exercise. Despite a 45-fold greater RET-induced exposure to testosterone in males than females in the early (1 h) recovery period, myofibrillar protein synthesis rates were similar between sexes (2.3- and 2.7-fold increase above rest in males and females, respectively) 1–5 h postexercise and after protein ingestion following 24 h recovery. These data indicate that the RET-induced increases in muscle protein synthesis are unaffected by postexercise elevations in testosterone and that myofibrillar protein synthesis is similar in females, even with much lower systemic testosterone concentrations (12). Finally, Morton and colleagues (13) trained 49 males where training was performed with either higher (8–10 repetitions/set) or lower (20–25 repetitions/set) loads. The authors reported similar muscle hypertrophy and strength improvements with no significant correlations between the acute postexercise rise in systemic hormones and any outcome, corroborating previous work that systemic hormonal increases are not related to or indicative of RET-induced gains in muscle hypertrophy or strength (13).

Due to the anabolic effect of testosterone, conceivably, females could have less potential to increase their muscle mass and strength than males (20). However, research has shown that females achieve relatively similar degrees of hypertrophy (57) and potentially even greater strength following RET (20). A meta-analysis by Roberts et al. (20) showed no sex-based differences in response to RET for strength or hypertrophy in young to middle-aged males and females following the same RET protocol. Researchers pooled 12 hypertrophy outcomes from 10 studies involving male and female participants engaged in RET ranging from 7 to 24 wk in duration. The pooled effect size for relative hypertrophy in males versus females was not statistically significant (effect size: 0.07, ±0.06; P = 0.31; I² = 0). Upper-body strength comprised 19 outcomes from 17 studies with a significant effect favoring females (effect size: −0.60, ±0.16; P = 0.002; I² = 72.1). The lower body strength analysis comprised 23 outcomes from 23 studies with no significant differences between sexes (effect size: −0.21 ± 0.16; P = 0.20; I² = 74.7). In addition, mechanisms contributing to muscle hypertrophy and strength, such as muscle protein synthesis and mTORc1 signaling, have been reported to be similar between sexes (4). Future research is needed to draw strong conclusions, but currently, these data suggest that, when considering relative changes, females have similar hypertrophy and strength gains compared to males following RET (20).

In summary, the acute postexercise rises in systemic testosterone, growth hormone, and IGF-1 are neither sufficient nor necessary for stimulating a rise in muscle protein synthesis, stimulating RET-induced gains in lean mass, increments in strength, or maximizing muscle hypertrophy. We find no good evidence to suggest that structuring RET to “take advantage” of higher anabolic hormones — testosterone, growth hormone, IGF-1 — is warranted in males or females. Comparisons of males to females regarding their RET-induced protein turnover and signaling show comparable relative increases, which casts doubt on the thesis around the importance of testosterone in anabolic processes. Although it could be argued that another hormone in females fulfills the same role as testosterone, no evidence shows or suggests that estrogen (or another hormone) could fulfill such a “compensatory” role given the low androgenicity of estrogen. In contrast to a systemic hormone-driven process, we propose (detailed extensively in two recent reviews (1,4)) that local muscular mechanotransducive mechanisms are the primary drivers of RET-induced changes in hormonal signaling and, ultimately, hypertrophy.

CURRENT EVIDENCE DOES NOT SUPPORT FEMALES PERIODIZE THEIR RET ACCORDING TO THEIR MENSTRUAL CYCLE PHASES

Although it has been proposed that periodizing RET with menstrual cycle phases could offer advantages due to hormonal fluctuations, current evidence does not support this approach (58,59). Estrogen peaks in the late follicular phase of the menstrual cycle before ovulation, whereas progesterone peaks after ovulation during the midluteal phase (26). Although the “textbook” menstrual cycle lasts 28 d, with ovulation occurring at day 14 (19), the reality is marked by remarkable variability both within and across females, adding layers of complexity to this approach (19). Studies investigating the impact of the menstrual cycle on performance and physiological adaptations lack methodological rigor, with inconsistencies in describing female cohorts contributing to the heterogeneity observed in the literature (37).

When investigating the role of ovarian hormones on exercise responses, it is crucial to recruit female participants based on predefined, standardized criteria, with retrospective confirmation. Additionally, establishing hormonal profiles for each participant through methods like calendar tracking, ovulation testing, and blood draws is essential. Cyclical acute fluctuations in ovarian hormones can be influenced by various factors such as hormonal contraceptives, daily stresses, exercise routines, and undiagnosed menstrual disorders or anovulatory cycles. These factors all increase the variability both within and between females necessitating researchers to control for, or at least characterize, menstrual cycle phase (37). These standards ensure that ovarian profiles are accurately characterized and measurements are appropriately aligned with the participant’s menstrual phase, reducing variability between studies (37).

However, researchers often assume a symmetrical, repeating menstrual cycle without adequate confirmation, leading to increased heterogeneity in outcomes. Researchers should strive for methodological consistency, employing clear terminology to describe participants and detailing inclusion/exclusion criteria, especially regarding hormonal parameters. Enhancing uniformity in research practices will facilitate more meaningful comparisons and advance our understanding of ovarian hormones and performance (37).

Although long-term declines in hormonal concentrations invariably have metabolic implications, the acute fluctuations in estrogen and progesterone during the menstrual cycle only last several days. A recent systematic review from Colenso-Semple and colleagues concluded that there is insufficient evidence to support the short-term influence of these hormonal fluctuations on acute or long-term adaptations to RET (26). Although more data are warranted to elucidate the role of estrogen and estrogen-receptor signaling in female physiology and their roles in RET adaptations (4), existing evidence does not consistently demonstrate metabolic or physiological changes at the muscle level suggestive of an estrogen (or progesterone)-mediated effect (19).

Given the current state of the literature and the hype surrounding phase-based training, it is premature and even misguided for females to plan and periodize their RET regimen based on hormonally-mediated advantages or disadvantages in certain phases of their menstrual cycle (19). However, continued research efforts with improved methodological consistency are needed to advance our understanding of ovarian hormones and their role in RET adaptations.

CONCLUSION AND PRACTICAL APPLICATION

The acute rise in anabolic hormones following exercise does not appear to significantly influence muscle protein synthesis or the hypertrophic and strength adaptations induced by RET in both males and females. Additionally, despite substantial differences in androgen concentrations, particularly testosterone, males and females experience similar relative gains in response to RET. These observations shed light on the question of whether androgens, particularly testosterone, play a substantial role in influencing muscle hypertrophy. We acknowledge, however, that the mechanisms of how males and females achieve RET-induced hypertrophy may be different.

Moreover, there is no strong evidence to support the notion that females should adjust their RET practices based on a specific phase of their menstrual cycle to promote adaptations. Encouraging females to align their exercise routines with certain menstrual cycle phases may limit their autonomy and contradict established coaching principles that prioritize individualized training (60,61).

It is crucial to differentiate between menstrual cycle–related symptoms and hormonal fluctuations when programming female training practices. Effective programming requires consideration of various factors, including physiological aspects (cramps, bloating, pain) and psychological (mood, cognition, behavior). However, it is important to recognize that these symptoms are not always present, and their severity can vary substantially from one individual to another, regardless of ovarian profile characteristics. Therefore, training should be tailored with flexibility to accommodate these variations and ensure optimal performance and well-being.

Finally, the menstrual cycle is characterized by extraordinary variation both between and within the same individual. Therefore, to fully elucidate the influence of ovarian hormones on key aspects of exercise physiology, researchers must employ gold-standard practices. Characterizing ovarian profiles and establishing the presence of menstrual cycle phases is imperative if the research question hinges on the role of ovarian hormones.