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Suppression of endogenous testosterone production attenuates the response to strength training: a randomized, placebo-controlled, and blinded intervention study
Abstract
We hypothesized that suppression of endogenous testosterone would inhibit the adaptations to strength training in otherwise healthy men. Twenty-two young men with minor experience with strength training participated in this randomized, placebo-controlled, double-blinded intervention study. The subjects were randomized to treatment with the GnRH analog goserelin (3.6 mg) or placebo (saline) subcutaneously every 4 wk for 12 wk. The strength training period of 8 wk, starting at week 4, included exercises for all major muscles [3–4 sets per exercise × 6–10 repetitions with corresponding 6- to 10-repetition maximum (RM) loads, 3/wk]. A strength test, blood sampling, and whole body DEXA scan were performed at weeks 4 and 12. Endogenous testosterone decreased significantly ( P < 0.01) in the goserelin group from 22.6 ± 5.5 (mean ± SD) nmol/l to 2.0 ± 0.5 ( week 4) and 1.1 ± 0.6 nmol/l ( week 12), whereas it remained constant in the placebo group. The goserelin group showed no changes in isometric knee extension strength after training, whereas the placebo group increased from 240.2 ± 41.3 to 264.1 ± 35.3 Nm ( P < 0.05 within and P = 0.05 between groups). Lean mass of the legs increased 0.37 ± 0.13 and 0.57 ± 0.30 kg in the goserelin and placebo groups, respectively ( P < 0.05 within and P = 0.05 between groups). Body fat mass increased 1.4 ± 1.0 kg and decreased 0.6 ± 1.2 kg in the goserelin and placebo groups, respectively ( P < 0.05 within and between groups). We conclude that endogenous testosterone is of paramount importance to the adaptation to strength training.
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“when bioavailable testosterone was reduced to castrate levels in young men, isometric strength did not increase after resistance exercise training [62].”
From Integrating Transwomen and Female Athletes with Differences of Sex Development (DSD) into Elite Competition: The FIMS 2021 Consensus Statement (2021) · cites this paper as [62]
In the citing paper
“Despite testosterone suppression to female levels of 2 nmol/L, there was a significant + 4% increase in leg lean mass and a + 2% increase in total lean body mass, and a measurable though insignificant increase in isometric knee extension strength.”
From Transgender Women in the Female Category of Sport: Perspectives on Testosterone Suppression and Performance Advantage (2021) · cites this paper as [93]
In the citing paper
“in select exercises used during the training program, 10RM leg press and bench press increased + 32% and + 17%, respectively.”
From Transgender Women in the Female Category of Sport: Perspectives on Testosterone Suppression and Performance Advantage (2021) · cites this paper as [93]
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“Similarly, exercise bouts that limit the anabolic hormonal response and/or exacerbate the catabolic hormonal response suppress adaptations compared with control exercise sessions (27, 32).”
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Laurent, M. R., Dedeyne, L., Dupont, J., Mellaerts, B., Dejaeger, M., & Gielen, E. (2019) · Maturitas · doi:10.1016/j.maturitas.2019.01.006 · Cited by 114
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“When endogenous testosterone release is blocked (via a gonadotropin-releasing hormone analog), strength and lean mass adaptations to training are severely attenuated (24).”
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“As previously published (Kvorning et al. 2006), only the placebo group showed a significant increase in isometric strength after 8 weeks of training (P < 0.”
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“(41) demonstrated that suppressing testosterone production via administration of a gonadotropin-releasing hormone analog (goserelin) significantly blunted hypertrophic adaptations in young men after an 8-week Journal of Strength and Conditioning Research the TM”
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Exercise and the regulation of skeletal muscle hypertrophy
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“mones (15,16,21,22,30), not all resistance exercise protocols”
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“1 3 important implications for modulating short- and longterm adaptations to resistance training, such as muscle protein synthesis, androgen receptor (AR) content and half-life, and/or intramuscular amino acid uptake, leading to improved net protein balance, muscle growth, and/or muscular strength/functional performan…”
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“However, because the suppression of endogenous testosterone can prevent these changes (31), it is likely that testosterone has some permissive roles (not necessarily dose dependent within a normal physiological range) in the training process.”
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Exercise and the control of muscle mass in human
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Headley, S., Henry, K., Nindl, B. C., Thompson, B. A., Kraemer, W. J., & Jones, M. T. (2010) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0b013e3181bf053b · Cited by 58
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“…also depend upon a number of other important factors such as the number of androgen receptors on the target tissues, intra-cellular signaling, locally produced (paracrine–autocrine) hormones, and differential isoform responses (Kraemer et al. 2006; Kraemer and Ratamess 2005; Kvorning et al. 2006).”
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Gentil, P., de Lira, C. A. B., Paoli, A., dos Santos, J. A. B., da Silva, R. D. T., Pereira, J. R., da Silva, E. P., & Magosso, R. F. (2017) · European Journal of Translational Myology · doi:10.4081/ejtm.2017.6247 · Cited by 58
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“Changes in circulating or local testosterone and/or androgen receptor (AR) levels have been observed after exercise or overloading (5, 39, 70), AR blockade can attenuate exercise-induced muscle hypertrophy (31, 37), and some clinical studies in different patient cohorts show that the combination of androgen therapy an…”
Kraemer, W. J., Hatfield, D. L., Spiering, B. A., Vingren, J. L., Fragala, M. S., Ho, J.-Y., Volek, J. S., Anderson, J. M., & Maresh, C. M. (2007) · European Journal of Applied Physiology · doi:10.1007/s00421-007-0535-3 · Cited by 51
“The signiWcance of testosterone in the adaptations to resistance training was recently highlighted by Kvorning et al. (2006), who found that chemical blockage of endogenous gonadal testosterone production in otherwise healthy young men prevented strength increases and limited hypertrophy following…”
BackgroundDose Effect of Caffeine on Testosterone and Cortisol Responses to Resistance Exercise
Beaven, C. M., Hopkins, W. G., Hansen, K. T., Wood, M. R., Cronin, J. B., & Lowe, T. E. (2008) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.18.2.131 · Cited by 71
“…unclear if its confidence interval overlapped the thresholds for substantiveness (that is, if the chances of the effect’s being substantially positive and negative were both >5%); otherwise the magnitude of the effect was reported as the magnitude of its observed value (Batterham & Hopkins, 2006).”
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“Those hormones and blood lactate have an effect on the changes occurring after a resistance training program because of interaction with specific androgen receptors (64).”
BackgroundEffect of resistance exercise on muscle steroidogenesis
Vingren, J. L., Kraemer, W. J., Hatfield, D. L., Anderson, J. M., Volek, J. S., Ratamess, N. A., Thomas, G. A., Ho, J., Fragala, M. S., & Maresh, C. M. (2008) · Journal of Applied Physiology · doi:10.1152/japplphysiol.91235.2008 · Cited by 51
“The importance of testosterone for muscle adaptations to resistance exercise training was recently highlighted by the finding that suppression of circulating testosterone concentrations prevented resistance training-induced hypertrophy in young, healthy men ( 26 ).”
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Salivary testosterone is related to self-selected training load in elite female athletes
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“It is accepted that a testosterone concentration within the normal physiological range is requisite and indispensible for a normal adaptive response to resistance exercise [22,28,37].”
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“Testosterone is the dominant anabolic marker for protein signaling in men (21,22,30).”
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“Moreover, circulating testosterone has been shown to affect increases in lean mass and strength during 12 wk of resistance training [29].”
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Cellular and molecular pathways controlling muscle size in response to exercise
Attwaters, M., & Hughes, S. M. (2021) · FEBS Journal · doi:10.1111/febs.15820 · Cited by 47
Lundberg, T. R., Tucker, R., McGawley, K., Williams, A. G., Millet, G. P., Sandbakk, Ø. B., Howatson, G., Brown, G. A., Carlson, L. A., Chantler, S., et al. (2024) · Scandinavian Journal of Medicine and Science in Sports · doi:10.1111/sms.14581 · Cited by 51
“63,64 Therefore, a rational hypothesis based on current evidence would be that retained male advantage would be larger, not smaller, in highly trained transgender women if they continued to train during testosterone suppression, compared with untrained or moderately trained individuals.”
Kvorning, T., Christensen, L. L., Madsen, K., Nielsen, J. L., Gejl, K. D., Brixen, K., & Andersen, M. (2013) · Journal of the American Geriatrics Society · doi:10.1111/jgs.12279 · Cited by 44
Self-citationCook, C. J., Beaven, C. M., Kilduff, L. P., & Drawer, S. (2012) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.22.3.157 · Cited by 44
Physical exercise, nutrition and hormones: three pillars to fight sarcopenia
Sgrò, P., Sansone, M., Sansone, A., Sabatini, S., Borrione, P., Romanelli, F., & Luigi, L. D. (2018) · The Aging Male · doi:10.1080/13685538.2018.1439004 · Cited by 44
Hulmi, J. J., Ahtiainen, J. P., Selänne, H., Volek, J. S., Häkkinen, K., Kovanen, V., & Mero, A. A. (2008) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2008.03.030 · Cited by 44
Endocrine Response Patterns to Acute Unilateral and Bilateral Resistance Exercise in Men
Migiano, M. J., Vingren, J. L., Volek, J. S., Maresh, C. M., Fragala, M. S., Ho, J., Thomas, G. A., Hatfield, D. L., Häkkinen, K., Ahtiainen, J. P., et al. (2010) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0b013e3181a92dc5 · Cited by 43
“When testosterone was reduced to castrate levels, the resistance training–induced increase in isometric strength was eliminated and muscle hypertrophy was attenuated in young men (16).”
BackgroundChen, Z., Zhang, Y., Lu, C., Zeng, H., Schumann, M., & Cheng, S. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00843 · Cited by 44
Ahtiainen, J. P., Lehti, M., Hulmi, J. J., Kraemer, W. J., Alén, M., Nyman, K., Selänne, H., Pakarinen, A., Komulainen, J., Kovanen, V., et al. (2011) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0b013e318202e449 · Cited by 41
“with the regulation of exercise-induced remodeling processes of skeletal muscle (11,12,15,25).”
BackgroundMusculoskeletal ageing and primary prevention
Nedergaard, A., Henriksen, K., Karsdal, M. A., & Christiansen, C. (2013) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2013.06.001 · Cited by 42
Intracrine and Myotrophic Roles of 5α-Reductase and Androgens
Yarrow, J. F., McCoy, S. C., & Borst, S. E. (2011) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e31823bfcbf · Cited by 38
Testosterone, physical activity, and somatic outcomes among Filipino males
Gettler, L. T., Agustin, S. S., & Kuzawa, C. W. (2010) · American Journal of Physical Anthropology · doi:10.1002/ajpa.21282 · Cited by 37
Ethanol Does Not Delay Muscle Recovery but Decreases Testosterone/Cortisol Ratio
Haugvad, A., Haugvad, L., Hamarsland, H., & Paulsen, G. (2014) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000000339 · Cited by 34
Hanson, E. D., Nelson, A. R., West, D. W. D., Violet, J. A., O’Keefe, L., Phillips, S. M., & Hayes, A. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-3383 · Cited by 34
“training responses may be compromised by ADT (32).”
BackgroundExercise and Regulation of Protein Metabolism
Atherton, P. J., Phillips, B. E., & Wilkinson, D. J. (2015) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2015.06.015 · Cited by 36
Resting steroid hormone concentrations in lifetime exercisers and lifetime sedentary males
Hayes, L. D., Sculthorpe, N. F., Herbert, P., Baker, J. S., Hullin, D. A., Kilduff, L. P., & Grace, F. (2014) · The Aging Male · doi:10.3109/13685538.2014.977246 · Cited by 32
“an interaction between circulating T concentrations and maintenance of muscle mass [10,11].”
BackgroundComparison of upper body strength gains between men and women after 10 weeks of resistance training
Gentil, P., Steele, J., Pereira, M. C., Castanheira, R. P. M., Paoli, A., & Bottaro, M. (2016) · PeerJ · doi:10.7717/peerj.1627 · Cited by 37
“Moreover, Kvorning et al. (2006) found that the effects of testosterone on strength gains could be even more pronounced than muscle mass gains.”
BackgroundThorsen, L., Nilsen, T. S., Raastad, T., Courneya, K. S., Skovlund, E., & Fosså, S. D. (2012) · BMC Cancer · doi:10.1186/1471-2407-12-123 · Cited by 29
“Nevertheless, the accumulation of muscle mass during the strength training intervention was reduced in the testosterone-suppressed group compared to the placebo treated controls [40].”
ResultHandelsman, D. J., Idan, A., Grainger, J., Goebel, C., Turner, L., & Conway, A. J. (2014) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2014.01.011 · Cited by 31
INSL3 in the muscolo-skeletal system
Toni, L. D., Agoulnik, A. I., Sandri, M., Foresta, C., & Ferlin, A. (2019) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2018.12.021 · Cited by 30
Schumann, M., Walker, S., Izquierdo, M., Newton, R. U., Kraemer, W. J., & Häkkinen, K. (2014) · European Journal of Applied Physiology · doi:10.1007/s00421-013-2813-6 · Cited by 28
Ultradian rhythmicity and induced changes in salivary testosterone
Beaven, C. M., Ingram, J. R., Gill, N. D., & Hopkins, W. G. (2010) · European Journal of Applied Physiology · doi:10.1007/s00421-010-1518-3 · Cited by 29
“Indeed, the contribution of testosterone and cortisol in realising the adaptive responses to resistance exercise have been previously reported (Hansen et al. 2001; Bird et al. 2006; Kvorning et al. 2006; Beaven et al. 2008a).”
BackgroundThe Acute Hormonal Response to the Kettlebell Swing Exercise
Budnar, R. G., Duplanty, A. A., Hill, D. W., McFarlin, B. K., & Vingren, J. L. (2014) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0000000000000474 · Cited by 28
“Deficiency of T in young men has been associated with decreased strength (23) and with reductions in strength outcomes from resistance training (19), whereas supraphysiological doses of T have been associated with increased muscle strength and hypertrophy (4).”
BackgroundPostresistance Exercise Ethanol Ingestion and Acute Testosterone Bioavailability
Vingren, J. L., Hill, D. W., Buddhadev, H. H., & Duplanty, A. A. (2013) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e31828d3767 · Cited by 28
Castration alters protein balance after high-frequency muscle contraction
Steiner, J. L., Fukuda, D. H., Rossetti, M. L., Hoffman, J. R., & Gordon, B. S. (2016) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00740.2016 · Cited by 29
“Similarly, administration of a gonadotropin-releasing hormone analog to deplete endogenous androgen production in humans reduced the overall change in lean leg mass and strength after a resistance exercise training program (21), further supporting an interaction between androgens and protein balance in response to res…”
BackgroundHamilton, B. R., Lima, G., Barrett, J., Seal, L., Kolliari-Turner, A., Wang, G., Karanikolou, A., Bigard, X., Löllgen, H., Zupet, P., et al. (2021) · Sports Medicine · doi:10.1007/s40279-021-01451-8 · Cited by 30
Pasiakos, S. M., Berryman, C. E., Karl, J. P., Lieberman, H. R., Orr, J. S., Margolis, L. M., Caldwell, J. A., Young, A., Montano, M. A., Evans, W. J., et al. (2017) · Contemporary Clinical Trials · doi:10.1016/j.cct.2017.05.001 · Cited by 29
Androgen interacts with exercise through the mTOR pathway to induce skeletal muscle hypertrophy
Zeng, F., Zhao, H., & Liao, J. (2017) · Biology of Sport · doi:10.5114/biolsport.2017.69818 · Cited by 26
“These data further support the notion that the mTOR pathway is an important part of a signalling network that is involved in regulation of the androgen-and exercise-induced remodelling processes of skeletal muscle [62-65].”
BackgroundHayes, L. D., & Elliott, B. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2018.01878 · Cited by 25
Genitourinary injuries and extremity amputation in Operations Enduring Freedom and Iraqi Freedom
Nnamani, N. S., Janak, J. C., Hudak, S. J., Rivera, J. C., Lewis, E. A., Soderdahl, D. W., & Orman, J. A. (2016) · The Journal of Trauma: Injury, Infection, and Critical Care · doi:10.1097/ta.0000000000001122 · Cited by 25
“Similar to the muscle-related changes that occur with age and naturally declining testosterone levels, young men with suppressed testosterone have lesser capacity for muscle protein synthesis and strength attainment.(20,21) Given the severity of concomitant amputations and other related trauma, impaired wound healing…”
BackgroundPhysiological basis behind ergogenic effects of anabolic androgens
Cheung, A. S., & Grossmann, M. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.01.047 · Cited by 25
Influence of upper-body exercise order on hormonal responses in trained men
Junior, R. F. S., Leite, R. D., Speretta, G. F. F., Maior, A. S., de Salles, B. F., de Souza, T. P., Vingren, J. L., & Willardson, J. M. (2013) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2012-0040 · Cited by 24
“The importance of circulating hormones for muscle adaptations to resistance exercise is highlighted by the findings that suppression of circulating testosterone concentrations prevents resistance-exercise-induced hypertrophy in young healthy men (Kvorning et al. 2006), and that strength increased more when exercise se…”
Nunes, P. R. P., Barcelos, L. C., de Oliveira, A. A., Júnior, R. F., Martins, F. M., Resende, E. A. M. R., & Orsatti, F. L. (2017) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0000000000001788 · Cited by 24
“Suppression of basal total and free TT results in decreased MPS, muscle hypertrophy, and strength (31), affecting muscle adaptation after RT (7,30,35).”
BackgroundThe bone-muscle unit: from mechanical coupling to soluble factors-mediated signaling
Malvandi, A. M., Gerosa, L., Banfi, G., & Lombardi, G. (2025) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2025.101367 · Cited by 22
Lønbro, S. (2013) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2013.07.008 · Cited by 23
“This is likely due to an increase in circulating testosterone which is involved in protein synthesis and the rebuilding of muscle mass [53].”
BackgroundChristensen, J. F., Andersen, J. L., Adamsen, L., Lindegaard, B., Mackey, A. L., Nielsen, R. H., Rørth, M. R., & Daugaard, G. (2011) · BMC Cancer · doi:10.1186/1471-2407-11-326 · Cited by 22
“In healthy subject it has been shown that suppression of testosterone attenuates the response to resistance training [49], however whether TC patients undergoing chemotherapy experience attenuated exercise response because of treatment induced hypogonadism is currently unknown.”
BackgroundGharahdaghi, N., Rudrappa, S. S., Brook, M. S., Farrash, W. F., IDRIS, I. R., Aziz, M. H. A., Kadi, F., Papaioannou, K., Phillips, B. E., Sian, T. S., et al. (2022) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12843 · Cited by 22
Kvorning, T., Kadi, F., Schjerling, P., Andersen, M., Brixen, K., Suetta, C., & Madsen, K. (2014) · Acta Physiologica · doi:10.1111/apha.12404 · Cited by 21
“…SCs in the goserelin group did not lead to a significant addition of myonuclei, which is seen, as expected, in the placebo group, where a significant addition of myonuclei in type II fibres occurs in parallel with a significant increase in lean leg mass (Kvorning et al. 2006).”
BackgroundMethodResultInfluentialSelf-citationSmilios, I., Tsoukos, P., Zafeiridis, A., Spassis, A. T., & Tokmakidis, S. P. (2013) · Applied Physiology Nutrition and Metabolism · doi:10.1139/apnm-2013-0147 · Cited by 21
“Changes in hormonal concentrations following a resistanceexercise session contribute to the regulation of long-term neuromuscular adaptations (Hansen et al. 2001; Kvorning et al. 2006; Rønnestad et al. 2011).”
BackgroundInfluential
Metadata
- Authors
- Kvorning, T., Andersen, M., Brixen, K., & Madsen, K.
- Affiliations
- University of Southern Denmark (DK)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2006-12
- Volume
- 291
- Issue
- 6
- Pages
- E1325-E1332
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2135253149
- Semantic Scholar
- 364e0f2a02d36d26e9937995f621cacc20eab156
- Cited by
- 176
- References
- 60
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 7 · 2023: 9 · 2022: 6 · 2021: 9 · 2020: 6 · 2019: 9 · 2018: 4 · 2017: 10 · 2016: 6 · 2015: 11 · 2014: 15 · 2013: 16 · 2012: 9
- FWCI
- 5.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- Funders
- AstraZeneca
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Sports Performance and Training
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- endogenous testosterone, goserelin, GnRH analogues, resistance training, training effects, muscle strength, lean body mass, fat mass, isometric knee extension, young men
- MeSH terms
- Adult, Androgen Antagonists, Body Composition, Diet, Double-Blind Method, Estrogens, Hormones, Humans, Isometric Contraction, Leg, Male, Organ Size, Testosterone, Weight Lifting, Exercise, Absorptiometry, Photon, Goserelin, Muscle, Skeletal
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