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Androgen Adjuncts

Androgen adjuncts — hCG, clomiphene citrate, enclomiphene, anastrozole, and other SERMs — serve as alternatives or complements to exogenous testosterone, primarily to preserve fertility, stimulate endogenous testosterone production, or optimize the testosterone-to-estradiol ratio. Per the AUA Testosterone Deficiency guideline 2018, clinicians may use aromatase inhibitors, hCG, SERMs, or combinations in men with TD who desire to maintain fertility (Conditional Recommendation; Grade C). Of the agents covered here, only hCG is FDA-approved for use in males — all other uses are off-label.[1]

For the primary TRT framework, see Testosterone replacement. For ED pharmacology, see PDE5 inhibitors and Intracavernosal injection agents.

Human chorionic gonadotropin (hCG)​

Mechanism. hCG is a glycoprotein structurally and functionally equivalent to pituitary LH. It stimulates Leydig cells to produce androgens, maintaining intratesticular testosterone (ITT) — the critical driver of spermatogenesis — while raising serum testosterone and preserving the HPT axis feedback loop.[2][3]

FDA-approved indications in males[2]

  1. Prepubertal cryptorchidism not due to anatomic obstruction
  2. Selected cases of hypogonadotropic hypogonadism (pituitary deficiency)

Available as urinary-derived hCG (Pregnyl, Novarel) and recombinant hCG (Ovidrel). Handelsman 2024 confirmed comparable testosterone effects between urinary and recombinant formulations despite formal non-bioequivalence (pooled half-life ~5.8 days).[4]

Clinical applications​

IndicationTypical regimenKey evidence
Hypogonadotropic hypogonadism — monotherapy1,000–3,000 IU SC 2–3×/week, titrated to eugonadal rangeHabous 2018 RCT: 5,000 IU 2×/week → 223% T increase[5]
Fertility induction in HHhCG + FSH analog for 12–24 moSpermatogenesis in ~80%, pregnancy ~50%; Muir 2025 meta-analysis of 41 studies (n = 1,673) — combined hCG + FSH outperforms hCG monotherapy on sperm output[3][6]
Adjunct to TRT for fertility preservation500 IU SC every other day alongside TRTHsieh 2013 retrospective (n = 26): no azoospermia; 9/26 contributed to pregnancy. AUA/ASRM 2024 notes literature too limited to formally recommend[7][8]
Recovery of spermatogenesis after TRT-induced azoospermiahCG ± FSH ± SERMEndocrine Society notes gonadotropin therapy can reinitiate spermatogenesis; recovery typically 6 mo, up to 2 y[9]

FDA-label regimens for HH:[2]

  • 500–1,000 IU 3×/week × 3 wk, then 2×/week × 3 wk, or
  • 4,000 IU 3×/week × 6–9 mo, then 2,000 IU 3×/week × 3 mo

Predictors of spermatogenic response — post-pubertal onset HH, absence of prior cryptorchidism, higher baseline testicular volume, higher baseline inhibin B.[3]

Adverse effects and practical considerations​

  • Gynecomastia (most common) — hCG-driven aromatase activity raises estradiol; may require AI co-administration
  • Estradiol elevation, injection-site reactions, headache, irritability, fatigue
  • Testicular enlargement (desired in HH)
  • Injection burden and cost — 2–3 injections/week

2020 FDA reclassification — availability impact​

In 2020, hCG was reclassified as a biologic under the Biologics Price Competition and Innovation Act, removing it from Section 503A compounding eligibility. This significantly raised cost; FDA-approved branded products (Pregnyl, Novarel) remain available but are substantially more expensive than the compounded formulations many patients previously used.[10]

Clomiphene citrate (CC)​

Mechanism. SERM that blocks estrogen-mediated negative feedback at the hypothalamus and pituitary → increased GnRH pulsatility → elevated LH and FSH → increased endogenous testosterone with preserved or enhanced spermatogenesis.[11]

CC is a racemic mixture of two stereoisomers:[12]

  • Enclomiphene (trans-isomer) — the active anti-estrogenic component; half-life ~10 h
  • Zuclomiphene (cis-isomer) — weakly estrogenic; half-life ~30 days — can accumulate with chronic dosing

FDA status: approved only for ovulatory dysfunction in women. All use in men is off-label.[11]

Dosing. Most common regimen: 25–50 mg PO daily or every other day, titrated to testosterone response.[13][14]

Efficacy — biochemical response​

StudynDesignT responseSymptom / durationRef
Krzastek 20194002-center retrospective88% eugonadism at >3 y77% symptom improvement; only 8% AEs[13]
Keihani 20203322-center retrospectiveMean +329 ng/dL; 73% had ≥200 ng/dL riseMedian 6 wk to first follow-up[15]
Habous 2018282Randomized 3-arm (CC vs hCG vs combination)223% increase from baseline (all arms equivalent)qADAM improved; CC + hCG > monotherapy on symptoms[5]
Ramasamy 201493Age-matched retrospective vs TRT247 → 504 ng/dLqADAM similar to TRT; TRT had greater libido[16]
Taylor 2010104RetrospectivePost-treatment 573 ng/dLADAM 4.9 → 2.1; cost ~$83/mo vs $265–270 for gels[17]
Anno 2025541-y retrospectiveSustained rise over 12 moAMS improved; sexual domain did NOT improve[18]

Key finding: baseline LH/FSH are not strong predictors of CC response — adequate biochemical response can be expected in most patients with normal or slightly elevated baseline gonadotropins.[15]

CC vs TRT — head-to-head profile​

  • Ramasamy 2014 — CC 504 ng/dL vs TRT injection 1,014 ng/dL; qADAM similar; TRT produced greater libido (4 vs 3; p = 0.04)[16]
  • Taylor 2010 — CC 573 ng/dL vs gel 553 ng/dL (equivalent); cost $83/mo (CC) vs $265–270/mo (gel)[17]

Long-term safety — Krzastek 400-patient / 7-y dataset[13]​

  • 88% eugonadism at >3 y with sustained efficacy up to 84 months
  • Only 8% AE rate — mood changes (5), blurred vision (3), breast tenderness (2)
  • No significant adverse events in any patient
  • Estradiol was significantly increased (expected pharmacologic effect)

Adverse effects​

  • Elevated estradiol — most consistent biochemical effect; can cause gynecomastia or mood changes
  • Visual disturbances (blurred vision, scotomata) — rare, typically reversible on discontinuation
  • Mood changes (~5% of long-term users), breast tenderness
  • Theoretical zuclomiphene accumulation with chronic use — the rationale for developing pure enclomiphene[12]

Limitations​

  • Requires intact HPT function — ineffective in primary hypogonadism (elevated LH/FSH)[11]
  • Sexual dysfunction may not resolve despite testosterone normalization (Anno 2025)[18]
  • No large RCT vs TRT on patient-oriented outcomes
  • Endocrine Society: "neither its efficacy nor its safety has been demonstrated in randomized trials" for hypogonadism[9]

Enclomiphene citrate (investigational)​

Rationale. Pure trans-isomer of clomiphene — avoids zuclomiphene accumulation and its potentially counter-productive estrogenic effects with chronic dosing.[12]

Mechanism. SERM → blocks estrogen feedback at hypothalamus/pituitary → increases LH/FSH → increases endogenous testosterone and preserves spermatogenesis.[19][20]

FDA status — INVESTIGATIONAL. Phase III data (ZA-304 and ZA-305) are complete but the FDA issued a Complete Response Letter; the drug remains unapproved.[12]

Clinical trial data​

TrialnDesignFinding
Kim 2016 (combined ZA-304/305 endpoints)LargePhase III: enclomiphene 12.5 / 25 mg vs testosterone gel vs placeboBoth enclomiphene doses raised T; FSH and LH increased with enclomiphene but decreased with T gel; enclomiphene maintained sperm concentration, while T gel markedly suppressed spermatogenesis[19]
Wiehle 2013 (Phase II PD/PK)48Enclomiphene 25 mg vs T gel × 6 wkMean TT 604 vs 500 ng/dL (p = 0.23, NS); enclomiphene preserved circadian pattern with morning peaks[21]
Wiehle 2014 (Phase IIB)12Proof-of-principle vs T gelEnclomiphene raised sperm to 75–334 × 10⁶/mL at 3–6 mo; T gel failed to keep counts above 20 × 10⁶/mL in most men[20]

Enclomiphene vs clomiphene citrate​

No head-to-head RCTs in men have been published. Theoretical advantages of enclomiphene:[12][22]

  • No zuclomiphene accumulation
  • More predictable pharmacokinetics
  • Potentially fewer mood-related side effects

Current availability​

Despite the lack of FDA approval, enclomiphene is available via compounding pharmacies and telehealth platforms — quality-control and appropriate-patient-selection concerns are meaningful, and regulatory status remains in flux.[10]

Anastrozole (aromatase inhibitor)​

Mechanism. Third-generation nonsteroidal AI that inhibits CYP19A1 (aromatase), blocking conversion of testosterone → estradiol. In men this produces:[23][24]

  • Decreased estradiol (peripheral aromatization blocked)
  • Increased testosterone (loss of estradiol-mediated HPT negative feedback → increased LH/FSH → Leydig cell stimulation)
  • Increased T/E2 ratio

FDA status: approved only for breast cancer in postmenopausal women. All use in men is off-label.[25]

Dosing in men​

Most common regimen: 1 mg PO daily; 1 mg twice weekly also effective (Leder 2004):[24]

DoseBioavailable TTotal TEstradiol
1 mg daily99 → 207 ng/dL343 → 572 ng/dL26 → 17 pg/mL
1 mg twice weekly115 → 178 ng/dL397 → 520 ng/dL27 → 17 pg/mL

Clinical applications​

1. Monotherapy for hypogonadism — particularly functional / obesity-driven. Obese men have high aromatase activity in adipose tissue; AI corrects the low T / high E2 phenotype.[24][26]

Colleluori 2020 — 6-month RCT of anastrozole + weight loss vs placebo + weight loss in obese hypogonadal men: AI arm had higher testosterone (p = 0.003), lower estradiol (p = 0.001), greater fat-mass loss (p = 0.04), but no additional improvement in muscle strength or hypogonadal symptoms beyond weight loss alone.[26]

2. TRT adjunct — estradiol control and gynecomastia management.[27] Particularly useful:

  • Injectable testosterone with supraphysiologic peaks driving aromatization
  • Gynecomastia or breast tenderness on TRT
  • Pellet-interval extension: Mechlin 2014 showed anastrozole + testosterone pellets maintained therapeutic T for 198 days vs 128 days with pellets alone, with significantly less gonadotropin suppression[27]

3. Male infertility — oligozoospermia with low T / high E2. Shoshany 2017 — anastrozole 1 mg daily improved endocrine parameters in 95.3% and improved sperm concentration and total motile count in ~25% of oligozoospermic patients; magnitude of sperm improvement correlated with T/E2 ratio change.[28]

Anastrozole vs clomiphene citrate — head-to-head RCT​

Helo 2015 (n = 26 hypogonadal infertile men, CC 25 mg/day vs anastrozole 1 mg/day × 12 wk):[29]

OutcomeCCAnastrozoleInterpretation
Final testosterone571 ng/dL408 ng/dLCC significantly higher
EstradiolIncreasedDecreasedOpposite effects
T/E2 ratio (12 wk)Increased (NS)Significantly increasedAI greater
Semen parametersNo changeNo changeNS
Patient-reported outcomesNo changeNo changeNS

Neither agent improved patient-reported outcomes or semen parameters over 12 weeks; CC produced higher T, AI produced higher T/E2 ratio.[29]

Critical safety concern — bone health​

Estradiol is the dominant regulator of male skeletal health; suppressing it with AI carries real risk:[30][31]

  • Burnett-Bowie 2009 1-y RCT (n = 69 elderly hypogonadal men) — anastrozole decreased posterior-anterior spine BMD vs placebo (p = 0.0014) despite raising testosterone. Conclusion: "Aromatase inhibition does not improve skeletal health in aging men."[31]
  • Leder 2005 12-wk study — no changes in bone turnover markers, but authors cautioned long-term use could be detrimental[32]
  • ATAC trial (postmenopausal women) — 5-y anastrozole caused 6.08% lumbar spine BMD loss and 7.24% total hip BMD loss. Extrapolation to men is directional, not quantitative[33]
  • Russell 2019 review — estradiol is important for male bone, body composition, and glucose metabolism; testosterone, not AI, is the treatment of choice for male hypogonadism[30]

Other adverse effects in men​

  • Cholesterol elevation (9% vs 3.5% tamoxifen in ATAC)[25]
  • Arthralgias / myalgias (well-described in breast-cancer populations)
  • Theoretical CV effects from estradiol suppression
  • No significant short-term effect on PSA, LUTS, hematocrit, or liver function[24]

Guideline positions​

  • AUA 2018 — AIs listed among options for fertility-preserving TD treatment (Conditional; Grade C)[1]
  • Endocrine Society 2018 — not recommended for hypogonadism treatment[9]
  • ISA/ISSAM/EAU/EAA/ASA 2009 — AIs raise endogenous T but "adequate evidence does not exist to recommend their use"[34]
  • Russell 2019 — do not prefer AIs over testosterone for male hypogonadism[30]

Other SERMs — tamoxifen and raloxifene​

Tamoxifen​

SERM at 20 mg PO daily. Increases LH ~70% and testosterone ~40% — significantly stronger HPT effect than raloxifene (LH +30%, testosterone +25%).[35] Reduces IGF-1 by ~25% and raises SHBG by ~20%, which can partially offset free-testosterone gains. In idiopathic oligozoospermia, tamoxifen raises androgens and sperm concentrations, though pregnancy-rate data are inconclusive.[36][37]

Raloxifene​

60 mg PO daily — weaker HPT effect than tamoxifen or clomiphene. Does not reduce IGF-1 or increase SHBG (potentially more favorable metabolic profile), but the weaker testosterone-raising effect limits utility.[35]

Neither tamoxifen nor raloxifene is commonly used in urologic practice for hypogonadism — clomiphene dominates the SERM space based on experience and data.[11]

Combination strategies​

CombinationRationaleEvidence
CC + hCGDual stimulation — central SERM + peripheral LH analogHabous 2018 RCT: 223% T increase; qADAM improved more than with either monotherapy[5]
CC + anastrozoleCC raises T but also E2; AI controls the E2 riseInvestigated; limited published data
TRT + hCGMaintains ITT and spermatogenesis during exogenous THsieh 2013 retrospective n = 26: no azoospermia; AUA/ASRM notes literature too limited to formally recommend[7][8]
TRT + anastrozoleControls TRT-induced E2 elevation; extends pellet durationMechlin 2014: 198 vs 128 days between pellet insertions[27]
hCG + FSHHH: hCG → Leydig cells; FSH → Sertoli cells / spermatogenesisMuir 2025 meta-analysis: combined > hCG alone for sperm; ~80% spermatogenesis, ~50% pregnancy[6]

Comparative summary​

AgentMechanismFDA-approved in malesTypical T effectPreserves fertilityKey advantageKey limitation
hCGLH analog → Leydig stimulationYes (HH)223% rise (RCT)Yes — maintains ITTOnly FDA-approved agent; direct testicular stimulationInjections 2–3×/wk; gynecomastia; cost post-2020 reclassification[2][5]
ClomipheneSERM → ↑ LH/FSHNo247 → 504 ng/dL (median)YesOral; ~$83/mo; 7-y safety dataOff-label; raises E2; zuclomiphene accumulation; sexual function may not improve[13][16]
EnclomiphenePure trans-SERMInvestigationalComparable to T gelYesNo zuclomiphene accumulation; preserves spermNot FDA-approved; compounding quality-control concerns[19][20]
AnastrozoleAI → ↓ E2, ↑ T/E2No343 → 572 ng/dLPartial — improves T/E2Best for high E2 / low T (e.g., obesity); TRT adjunctBone loss with chronic use; lower T than CC; insufficient guideline support[24][29][31]
TamoxifenSERM (stronger than raloxifene)No~40% riseYesRaises sperm concentrationReduces IGF-1; raises SHBG; less data than CC[35]

Clinical decision-making​

  • Hypogonadal man desiring fertility NOW — hCG (± FSH if HH) or clomiphene citrate first-line; avoid exogenous testosterone[8][1]
  • Hypogonadal man desiring fertility IN THE FUTURE — clomiphene or hCG as primary therapy; if TRT chosen, consider adding low-dose hCG (limited evidence)[7][8]
  • Hypogonadal man NOT desiring fertility — TRT remains the standard; CC or hCG are alternatives for men who prefer to avoid exogenous testosterone or its side effects (erythrocytosis, testicular atrophy)[13][16]
  • Elevated estradiol on TRT (gynecomastia, mood) — anastrozole 0.5–1 mg 2–3×/week as adjunct; monitor bone[27]
  • Obese man with functional hypogonadism — weight loss is first-line; CC or AI may be considered as adjuncts, though AI + weight loss did not improve symptoms beyond weight loss alone[26]
  • Recovery from TRT-induced azoospermia — hCG ± FSH ± CC; recovery typically within 6 mo but may take up to 2 y[9][10]
  • Primary hypogonadism (elevated LH/FSH) — SERMs and AIs are ineffective; TRT is the only option[11]

Evidence Summary​

ApplicationAgent(s)Evidence levelKey source
Fertility-preserving T restorationCC, hCG, CC + hCGLevel 1 (RCT)Habous 2018[5]; AUA/ASRM 2024[8]
HH — spermatogenesis inductionhCG + FSHLevel 1 (meta-analysis)Muir 2025[6]
CC long-term safetyClomipheneLevel 3 (retrospective, 7 y)Krzastek 2019[13]
CC vs TRT efficacyClomipheneLevel 2Ramasamy 2014[16]; Taylor 2010[17]
Enclomiphene efficacy + sperm preservationEnclomipheneLevel 1 (Phase III)Kim 2016[19]; Wiehle 2014[20]
Anastrozole efficacy on T and T/E2AnastrozoleLevel 1 (RCT)Leder 2004[24]; Helo 2015[29]
Anastrozole bone concernAnastrozoleLevel 1Burnett-Bowie 2009[31]; ATAC[33]
TRT + AI pellet extensionAnastrozole + pelletsLevel 3Mechlin 2014[27]

Clinical Positioning​

  • Only hCG is FDA-approved for use in males — all other agents covered here are off-label with the AUA 2018 fertility-preservation pathway as the primary guideline support.[1][2]
  • For fertility preservation, CC and hCG are equivalent on testosterone restoration and patient-reported outcomes per Habous 2018 — choose based on injection tolerance, cost, and patient preference; combination produces greater symptom improvement than either alone.[5]
  • Clomiphene is the dominant SERM for male hypogonadism — $83/month, oral, 7-year safety data in 400 patients, 88% eugonadism at 3 years.[13][17]
  • Sexual function may not respond even when testosterone normalizes on CC (Anno 2025). Counsel accordingly; do not promise libido restoration.[18]
  • Enclomiphene is not FDA-approved. The Phase III data are encouraging but the Complete Response Letter remains in force; compounding-pharmacy availability raises quality-control concerns.[12]
  • Anastrozole is a TRT-adjunct agent, not a monotherapy in most patients — the Helo 2015 head-to-head showed CC produced higher testosterone and AI produced higher T/E2 ratio; neither improved PROs. For monotherapy, CC is preferred.[29]
  • Anastrozole bone concern is load-bearing. Burnett-Bowie 2009 showed BMD loss at 1 year despite T elevation. If using AI chronically, monitor BMD and consider concurrent bone-protective therapy.[31]
  • TRT + hCG to preserve fertility is a common but evidence-thin approach — AUA/ASRM 2024 notes the literature is too limited for formal recommendation; Hsieh 2013 is the supporting retrospective series.[7][8]
  • hCG + FSH is the proper regimen for fertility induction in HH — Muir 2025 meta-analysis confirms the combination outperforms hCG alone; 80% spermatogenesis and 50% pregnancy rates are the expectations.[6]
  • SERMs and AIs are ineffective in primary hypogonadism — if LH/FSH are elevated at baseline, the testes cannot respond further; only TRT addresses the deficit.[11]
  • 2020 hCG reclassification raised cost substantially — counsel patients on branded-product price (Pregnyl/Novarel) and consider cost when selecting between hCG and clomiphene for equivalent indications.[10]

See Also​

References​

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2. US Food and Drug Administration. Chorionic gonadotropin — prescribing information. Updated 2025-04-11.

3. Boeri L, Capogrosso P, Salonia A. "Gonadotropin treatment for the male hypogonadotropic hypogonadism." Curr Pharm Des. 2021;27(24):2775–2783. doi:10.2174/1381612826666200523175806

4. Handelsman DJ, Idan A, Desai R, et al. "Single and multi-dose pharmacology of recombinant and urinary human chorionic gonadotrophin in men." Clin Endocrinol. 2024;101(1):42–50. doi:10.1111/cen.15040

5. Habous M, Giona S, Tealab A, et al. "Clomiphene citrate and human chorionic gonadotropin are both effective in restoring testosterone in hypogonadism: a short-course randomized study." BJU Int. 2018;122(5):889–897. doi:10.1111/bju.14401

6. Muir CA, Zhang T, Jayadev V, Conway AJ, Handelsman DJ. "Efficacy of gonadotropin treatment for induction of spermatogenesis in men with pathologic gonadotropin deficiency: a meta-analysis." Clin Endocrinol. 2025;102(2):167–177. doi:10.1111/cen.15151

7. Hsieh TC, Pastuszak AW, Hwang K, Lipshultz LI. "Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy." J Urol. 2013;189(2):647–650. doi:10.1016/j.juro.2012.09.043

8. Brannigan RE, Hermanson L, Kaczmarek J, et al. "Updates to male infertility: AUA/ASRM guideline (2024)." J Urol. 2024;212(6):789–799. doi:10.1097/JU.0000000000004180

9. Bhasin S, Brito JP, Cunningham GR, et al. "Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline." J Clin Endocrinol Metab. 2018;103(5):1715–1744. doi:10.1210/jc.2018-00229

10. Naelitz BD, Momtazi-Mar L, Vallabhaneni S, et al. "Testosterone replacement therapy and spermatogenesis in reproductive-age men." Nat Rev Urol. 2025. doi:10.1038/s41585-025-01032-8

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13. Krzastek SC, Sharma D, Abdullah N, et al. "Long-term safety and efficacy of clomiphene citrate for the treatment of hypogonadism." J Urol. 2019;202(5):1029–1035. doi:10.1097/JU.0000000000000396

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16. Ramasamy R, Scovell JM, Kovac JR, Lipshultz LI. "Testosterone supplementation versus clomiphene citrate for hypogonadism: an age-matched comparison of satisfaction and efficacy." J Urol. 2014;192(3):875–879. doi:10.1016/j.juro.2014.03.089

17. Taylor F, Levine L. "Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism: efficacy and treatment cost." J Sex Med. 2010;7(1 Pt 1):269–276. doi:10.1111/j.1743-6109.2009.01454.x

18. Anno Y, Tsujimura A, Kasai R, et al. "Efficacy and safety of clomiphene citrate for late-onset hypogonadism as evaluated by Aging Male Symptom Rating Scale over one year." Int J Urol. 2025. doi:10.1111/iju.70289

19. Kim ED, McCullough A, Kaminetsky J. "Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: restoration instead of replacement." BJU Int. 2016;117(4):677–685. doi:10.1111/bju.13337

20. Wiehle RD, Fontenot GK, Wike J, et al. "Enclomiphene citrate stimulates testosterone production while preventing oligospermia: a randomized Phase II clinical trial comparing topical testosterone." Fertil Steril. 2014;102(3):720–727. doi:10.1016/j.fertnstert.2014.06.004

21. Wiehle R, Cunningham GR, Pitteloud N, et al. "Testosterone restoration by enclomiphene citrate in men with secondary hypogonadism: pharmacodynamics and pharmacokinetics." BJU Int. 2013. doi:10.1111/bju.12363

22. Joseph T, Gibbs LM, Pham K. "Are SERMs safe and effective for the treatment of hypogonadism in men?" J Fam Pract. 2022;71(1):E18–E21. doi:10.12788/jfp.0342

23. Yang C, Li P, Li Z. "Clinical application of aromatase inhibitors to treat male infertility." Hum Reprod Update. 2021;28(1):30–50. doi:10.1093/humupd/dmab036

24. Leder BZ, Rohrer JL, Rubin SD, Gallo J, Longcope C. "Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels." J Clin Endocrinol Metab. 2004;89(3):1174–1180. doi:10.1210/jc.2003-031467

25. US Food and Drug Administration. ARIMIDEX (anastrozole) — prescribing information. Updated 2026-03-02.

26. Colleluori G, Chen R, Turin CG, et al. "Aromatase inhibitors plus weight loss improves the hormonal profile of obese hypogonadal men without causing major side effects." Front Endocrinol. 2020;11:277. doi:10.3389/fendo.2020.00277

27. Mechlin CW, Frankel J, McCullough A. "Coadministration of anastrozole sustains therapeutic testosterone levels in hypogonadal men undergoing testosterone pellet insertion." J Sex Med. 2014;11(1):254–261. doi:10.1111/jsm.12320

28. Shoshany O, Abhyankar N, Mufarreh N, Daniel G, Niederberger C. "Outcomes of anastrozole in oligozoospermic hypoandrogenic subfertile men." Fertil Steril. 2017;107(3):589–594. doi:10.1016/j.fertnstert.2016.11.021

29. Helo S, Ellen J, Mechlin C, et al. "A randomized prospective double-blind comparison trial of clomiphene citrate and anastrozole in raising testosterone in hypogonadal infertile men." J Sex Med. 2015;12(8):1761–1769. doi:10.1111/jsm.12944

30. Russell N, Grossmann M. "Mechanisms in endocrinology: estradiol as a male hormone." Eur J Endocrinol. 2019;181(1):R23–R43. doi:10.1530/EJE-18-1000

31. Burnett-Bowie SA, McKay EA, Lee H, Leder BZ. "Effects of aromatase inhibition on bone mineral density and bone turnover in older men with low testosterone levels." J Clin Endocrinol Metab. 2009;94(12):4785–4792. doi:10.1210/jc.2009-0739

32. Leder BZ, Finkelstein JS. "Effect of aromatase inhibition on bone metabolism in elderly hypogonadal men." Osteoporos Int. 2005;16(12):1487–1494. doi:10.1007/s00198-005-1890-8

33. Eastell R, Adams JE, Coleman RE, et al. "Effect of anastrozole on bone mineral density: 5-year results from the Anastrozole, Tamoxifen, Alone or in Combination trial 18233230." J Clin Oncol. 2008;26(7):1051–1057. doi:10.1200/JCO.2007.11.0726

34. Wang C, Nieschlag E, Swerdloff RS, et al. "ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males." Aging Male. 2009;12(1):5–12. doi:10.1080/13685530802389628

35. Birzniece V, Sata A, Sutanto S, Ho KK. "Neuroendocrine regulation of growth hormone and androgen axes by selective estrogen receptor modulators in healthy men." J Clin Endocrinol Metab. 2010;95(12):5443–5448. doi:10.1210/jc.2010-1477

36. Dimakopoulou A, Foran D, Jayasena CN, Minhas S. "Stimulation of Leydig and Sertoli cellular secretory function by anti-oestrogens: tamoxifen." Curr Pharm Des. 2021;27(23):2682–2691. doi:10.2174/1381612826666200213095228

37. Tsourdi E, Kourtis A, Farmakiotis D, et al. "The effect of selective estrogen receptor modulator administration on the hypothalamic-pituitary-testicular axis in men with idiopathic oligozoospermia." Fertil Steril. 2009;91(4 Suppl):1427–1430. doi:10.1016/j.fertnstert.2008.06.002