Clomiphene
Clomiphene has randomized live-birth evidence for selected female ovulatory infertility. In selected men with functional secondary hypogonadism it reliably raises LH, FSH, and testosterone. Symptom and fertility outcomes are mixed, post-AAS recovery data are weak, and healthy performance has not been tested.
Mixed-isomer selective estrogen-receptor modulator used for ovulation induction
- US approval is for selected women with ovulatory dysfunction who desire pregnancy.
- Selected low-testosterone men often show a large hormone response; symptom and sexual outcomes are much less certain.
- The largest male-fertility placebo trial was negative. A newer small trial improved semen measures without measuring pregnancy or live birth.
- Post-cycle studies mix clomiphene with natural recovery, treatment choice, hCG, testosterone, and other medicines.
- Visual toxicity, ovarian hyperstimulation, multiple pregnancy, rising estradiol, lipid changes, and long isomer persistence matter.
What is clomiphene FDA approved to treat?
Its US indication is selected ovulatory dysfunction in women who want pregnancy after appropriate evaluation. Male hypogonadism, male infertility, post-AAS recovery, and enhancement are off-label uses. The male evidence has to stand on its own outcomes.
US label · female ovulatory dysfunction and major warnings
FDA prescribing information
Cosette Pharmaceuticals, Inc. CLOMIPHENE CITRATE tablets. DailyMed setid 2ca373c1-4dba-4126-8616-5c533d606fe5. Updated January 31, 2025.
The US label covers ovulatory dysfunction in women desiring pregnancy, describes the mixed cis/trans isomer product, and warns about visual disorders, ovarian hyperstimulation, multiple pregnancy, liver disease, hypertriglyceridemia/pancreatitis, and prolonged isomer persistence. It says adequate controlled male-infertility efficacy evidence is absent.
- Participants / model
- Women with ovulatory dysfunction who desire pregnancy; label discussion also addresses unsupported male use
- Treatment
- Oral clomiphene citrate tablets
- Follow-up
- Current product record; treatment is cycle-limited in the label
- Study design
- Regulatory prescribing information
The label is not a male-hypogonadism or bodybuilding approval and does not provide a universal clomiphene half-life because the isomers persist differently.
Read the original sourcePubChem CID 2800 · clomiphene base identity
Government substance database
National Library of Medicine. PubChem Compound Summary for CID 2800, Clomiphene.
Identifies clomiphene base as C26H28ClNO, molecular weight 406.0 g/mol, CID 2800.
- Participants / model
- Not applicable
- Treatment
- Not applicable
- Follow-up
- Living database record
- Study design
- Curated chemical identity record
The marketed citrate salt is a mixed-isomer product and has a different formula and molecular weight from the base record.
Read the original sourceWhat do live-birth trials show for PCOS infertility?
In 626 women with PCOS, live birth was 22.5% with clomiphene, 7.2% with metformin, and 26.8% with both; adding metformin did not beat clomiphene (p=0.31). Dropout was 26.3%, 34.6%, and 23.4%, and multiple pregnancy among pregnancies was 6.0%, 0%, and 3.1%. In a later trial of 750 women, live birth was 27.5% with letrozole and 19.1% with clomiphene, an absolute difference of 8.4 percentage points (rate ratio 1.44, p=0.007). Twin pregnancy was 3.4% versus 7.4%, but that comparison was underpowered.
| Trial | Clomiphene | Comparator | Statistical result |
|---|---|---|---|
| Clomiphene/metformin, n=626 | 47/209 (22.5%) live birth | Metformin 15/208 (7.2%); combination 56/209 (26.8%) | Combination vs clomiphene p=0.31; dropout 23% to 35% |
| Letrozole comparison, n=750 | 72/376 (19.1%) live birth | Letrozole 103/374 (27.5%) | Absolute difference 8.4 points; rate ratio 1.44; p=0.007 |
PCOS infertility · 626 participants and live birth
Randomized double-blind multicenter trial
Richard S. Legro, Huiman X. Barnhart, William D. Schlaff, et al.; Cooperative Multicenter Reproductive Medicine Network. New England Journal of Medicine. 2007. PMID 17287476.
Live birth was 47/209 (22.5%) with clomiphene, 15/208 (7.2%) with metformin, and 56/209 (26.8%) with both; combination versus clomiphene was p=0.31. Dropout was 26.3%, 34.6%, and 23.4%, respectively.
- Participants / model
- 626 infertile women with polycystic ovary syndrome
- Treatment
- Clomiphene, extended-release metformin, or both
- Follow-up
- Up to 6 months, then pregnancy follow-up
- Study design
- Randomized double-blind multicenter comparative trial
- Funding
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
No ultrasound follicle monitoring, hCG trigger, or intrauterine insemination was used. Multiple-pregnancy percentages use pregnancies as denominator; serious events were mostly pregnancy complications.
Read the original sourcePCOS infertility · letrozole outperformed clomiphene
Randomized double-blind multicenter trial
Richard S. Legro, Robert G. Brzyski, Michael P. Diamond, et al.; NICHD Reproductive Medicine Network. New England Journal of Medicine. 2014. PMID 25006718.
Live birth was 103/374 (27.5%) with letrozole and 72/376 (19.1%) with clomiphene (rate ratio 1.44, 95% CI 1.10 to 1.87; p=0.007). Ovulation was 61.7% versus 48.3% of cycles. Twin pregnancy was 3.4% versus 7.4%, without a significant difference.
- Participants / model
- 750 infertile women aged 18 to 40 with polycystic ovary syndrome and defined reproductive eligibility
- Treatment
- Letrozole versus clomiphene
- Follow-up
- Up to five treatment cycles with pregnancy follow-up
- Study design
- Randomized double-blind multicenter comparative trial
- Funding
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
PCOS eligibility included reproductive anatomy and partner semen criteria. The study was underpowered for twins and congenital anomalies; 73.1% of infants received the planned registry physical examination.
Read the original sourceDoes clomiphene improve male fertility or preserve spermatogenesis?
Clomiphene maintains gonadotropin signaling and may improve semen measures in selected men. A pregnancy or live-birth benefit from treating the male partner has not been shown. The largest pregnancy-oriented placebo trial was negative. A newer small trial improved sperm concentration and motility without measuring pregnancy; a current cohort found a modest median gain and 29% of men worsened.
| Study | Population and design | Absolute result | Limit |
|---|---|---|---|
| WHO 1992 | 190 couples; multicenter double-blind placebo trial; six months | Semen unchanged; eight-month cumulative pregnancy 8.1% clomiphene vs 11.7% placebo | No benefit in this idiopathic-infertility population |
| Bangladesh placebo trial | 50 eugonadal men with idiopathic oligoasthenozoospermia randomized; 46 analyzed; 12 weeks | Sperm concentration 9.17→13.88 million/mL; progressive motility 14.67%→21.42%; total motile count 3.53→7.81 million | No pregnancy or live birth; single center, short, and registered after completion |
| Pozzi 2026 cohort | 166 hypogonadal oligospermic men; retrospective; median four months | Median sperm concentration 4.0→5.6 million/mL; 118 improved and 48 worsened | No control or pregnancy outcome; adverse-event discontinuations were excluded |
| Clomiphene plus vitamin E | 60 men randomized to the combination or placebo; six months | Pregnancy 11/30 vs 4/30; OR 3.76, 95% CI 1.03 to 13.64 | Vitamin E prevents attribution to clomiphene alone; the estimate is imprecise |
Randomized sperm comparisons against testosterone gel commonly cited in this context used enclomiphene alone. Clomid contains both enclomiphene and longer-persisting zuclomiphene.
WHO male-infertility trial · no efficacy
Randomized double-blind placebo-controlled multicenter trial
World Health Organization. International Journal of Andrology. 1992. PMID 1516979.
Among 190 couples, six months of male clomiphene did not improve semen quality. Eight-month cumulative pregnancy was 8.1% with clomiphene versus 11.7% with placebo.
- Participants / model
- 190 couples with idiopathic male semen-quality impairment and no major untreated female-factor infertility
- Treatment
- Oral clomiphene citrate versus placebo to male partners
- Follow-up
- 6 months of treatment; pregnancy assessed through 8 months
- Study design
- Multicenter randomized double-blind placebo-controlled trial
The trial studied idiopathic male infertility, not biochemically confirmed secondary hypogonadism; pregnancy is a couple-level outcome.
Read the original sourceBangladesh placebo RCT · semen outcomes
Randomized double-blind placebo-controlled trial
Hossain MJ, et al. Clinical and Experimental Reproductive Medicine. 2025. PMID 40899280. DOI 10.5653/cerm.2024.07353.
Among 46 analyzed men, clomiphene improved sperm concentration 9.17→13.88 million/mL, progressive motility 14.67%→21.42%, total motile count 3.53→7.81 million, and testosterone 372→806 ng/dL. Nausea occurred in two and dizziness in three.
- Participants / model
- 50 eugonadal men with idiopathic oligoasthenozoospermia randomized; 46 analyzed
- Treatment
- Clomiphene citrate versus placebo
- Follow-up
- 12 weeks
- Study design
- Single-center randomized double-blind placebo-controlled trial
No pregnancy or live-birth endpoint. The trial was registered after completion; funding was not stated and no relevant conflict was reported.
Read the original sourcePozzi et al. · 166-man sperm-response cohort
Retrospective cohort
Pozzi E, De Luca S, Birolini G, et al. World Journal of Men's Health. 2026. PMID 42533482. DOI 10.5534/wjmh.250371.
151/166 reached testosterone ≥3.5 ng/mL. Median sperm concentration rose 4.0→5.6 million/mL; 118 improved and 48 worsened by a median 3.3 million/mL.
- Participants / model
- 166 hypogonadal oligospermic men
- Treatment
- Clomiphene citrate
- Follow-up
- At least 3 months; median follow-up 4 months
- Study design
- Single-center retrospective cohort
No comparator or pregnancy outcome, 11% dropout, exclusion of adverse-event discontinuations, and a white-European cohort limit inference. The authors reported no disclosure.
Read the original sourceGhanem et al. · clomiphene plus vitamin E
Randomized placebo-controlled combination trial
Ghanem H, Shaeer O, El-Segini A. Fertility and Sterility. 2010;93(7):2232-2235. PMID 19268928.
Pregnancy occurred in 11/30 couples assigned clomiphene plus vitamin E and 4/30 assigned placebo; OR 3.76 (95% CI 1.03 to 13.64).
- Participants / model
- 60 men with idiopathic infertility and their partners
- Treatment
- Clomiphene plus vitamin E versus placebo
- Follow-up
- 6 months
- Study design
- Randomized controlled combination-treatment trial
Vitamin E prevents attribution to clomiphene alone, and the confidence interval is wide.
Read the original sourceHow strong is the evidence for low testosterone and symptoms in men?
The hormone effect is repeatable in selected men with a responsive pituitary and testes. In the best placebo trial, mean testosterone rose from about 226 to 688 ng/dL over 12 weeks while placebo stayed near 220. The same trial found no between-group improvement in its aggregate symptom score or most sexual complaints, no fat loss or endothelial benefit, and an HDL fall. Uncontrolled cohorts often report symptom improvement, but blinded evidence remains mixed.
| Evidence | Hormone result | Symptoms or durability | Limit |
|---|---|---|---|
| Soares placebo RCT | Total testosterone about 225.5→687.9 ng/dL over 12 weeks | No between-group aggregate symptom or most sexual-complaint benefit; lean mass +2.2 kg; HDL −8.5 mg/dL | 67/78 analyzed; obese symptomatic men with T ≤300; short and single center |
| Habous active-comparator RCT | Testosterone rose in clomiphene, hCG, and combination groups | qADAM improved in all arms | No placebo; abstract reports n=282 while group counts total 283 |
| Krzastek long-term cohort | Among 120 men treated beyond three years, 88% were eugonadal | 77% reported symptom improvement; 8% reported side effects | Retrospective study of selected long-term continuers; no comparator |
| Huijben cohort | Mean testosterone 9→16 nmol/L; it fell after 48/52 withdrawal trials | 74% reported improvement; adverse-event documentation was absent in 130/153 charts | Heterogeneous retrospective cohort with loss, stopping, and switching |
| Kim 2026 cohort | 136/292 (47%) met ≥400 ng/dL plus a ≥200-ng/dL rise | No symptom outcome | Short retrospective assessment; higher LH and prior androgen deprivation predicted failure |
78 men · hormones and body-composition surrogates
Randomized double-blind placebo-controlled trial
Andressa Heimbecher Soares, Nidia Celeste Horie, Lucas Augusto Piccinin Chiang, et al. International Journal of Obesity. 2018. PMID 29777228.
Seventy-eight men were randomized and 67 analyzed at 12 weeks. Hormones and several lean-mass measures rose; BMI, waist, fat mass, endothelial function, and most sexual complaints were unchanged, and HDL fell. No clomiphene participant discontinued for an adverse event.
- Participants / model
- 78 men with obesity-associated secondary hypogonadism randomized; 67 analyzed at 12 weeks
- Treatment
- Oral clomiphene citrate versus placebo
- Follow-up
- 12 weeks
- Study design
- Single-center randomized double-blind placebo-controlled trial
Short single-center surrogate trial without a testosterone-replacement comparator, fertility endpoints, long-term symptoms, or cardiovascular outcomes; diet and activity were not standardized.
Read the original sourceHabous et al. · clomiphene vs hCG vs combination
Randomized active-comparator trial
Habous M, Giona S, Tealab A, et al. BJU International. 2018;122(5):889-897. PMID 29772111. DOI 10.1111/bju.14401.
The abstract reports testosterone and qADAM improvement in clomiphene, hCG, and combination arms, with the largest qADAM gain in the combination arm.
- Participants / model
- Men with hypogonadism; abstract reports total n=282 while listed group counts sum to 283
- Treatment
- Clomiphene, hCG, or both
- Follow-up
- 3 months
- Study design
- Randomized active-comparator study without placebo
No semen or pregnancy endpoint. The abstract does not resolve the adverse-event, funding, or denominator details.
Read the original sourceKrzastek et al. · 400-man retrospective cohort
Retrospective two-center cohort
Krzastek SC, Sharma D, Abdullah N, et al. Journal of Urology. 2019;202(5):1029-1035. PMID 31216250. DOI 10.1097/JU.0000000000000396.
Of 400 treated men, 120 remained treated beyond three years; in that selected group 88% were eugonadal, 77% reported symptom improvement, and 8% reported side effects.
- Participants / model
- 400 men treated for hypogonadism; 120 treated longer than three years
- Treatment
- Clomiphene citrate
- Follow-up
- Mean 25.5 months; selected subgroup beyond 3 years
- Study design
- Retrospective two-center cohort
No untreated control and strong survivor or continuation selection.
Read the original sourceHuijben et al. · response, withdrawal, and chart gaps
Retrospective cohort
Huijben M, Huijsmans RLN, Lock MTWT, de Kemp VF, de Kort LMO, van Breda JHMK. Endocrinology, Diabetes & Metabolism. 2023;6:e416. PMID 36998229.
Mean testosterone rose 9→16 nmol/L and 74% reported improvement. Testosterone fell after 48/52 withdrawal trials. Recorded adverse events occurred in 16/153, but adverse-event documentation was absent in 130 charts.
- Participants / model
- 153 heterogeneous men treated for hypogonadism
- Treatment
- Clomiphene citrate
- Follow-up
- Retrospective follow-up with variable duration and withdrawal trials
- Study design
- Single-center retrospective cohort
No validated symptom tool or control. At endpoint only 43 remained followed; 26 were lost, 71 stopped, and 14 switched to testosterone. Authors reported no funding or conflicts.
Read the original sourceKim et al. · stricter biochemical response cohort
Retrospective response-predictor cohort
Kim JK, et al. Journal of Sexual Medicine. 2026. PMID 42251758. DOI 10.1093/jsxmed/qdag159.
136/292 men (47%) reached testosterone ≥400 ng/dL plus a ≥200-ng/dL rise within 12 weeks. Higher baseline LH predicted lower response odds, and prior androgen-deprivation therapy had OR 0.11.
- Participants / model
- 292 men with low or borderline testosterone plus symptoms or objective signs
- Treatment
- Clomiphene citrate
- Follow-up
- Response assessed within 12 weeks
- Study design
- Retrospective clinical cohort
- Funding
- NIH/NCI core support listed; no declared conflict
No symptom outcomes and short follow-up; the response definition is stricter than simple normalization.
Read the original sourceWhy do the local studies not overturn the larger trials?
The Russian report described 6 conceptions among 30 men receiving clomiphene. Treatment was not randomized and untreated controls chose observation. The Bangladesh placebo trial improved semen measures but measured no pregnancy. A Chinese abstract in women used the same herbal co-treatment in both arms and favored letrozole for ovulation and pregnancy without measuring live birth. The WHO male-pregnancy result remained negative.
Russian report · nonrandomized male-infertility comparison
Russian prospective clinical comparative study
N. S. Kravtsova, R. V. Rozhivanov, and D. G. Kurbatov. Проблемы эндокринологии. 2016;62(2):37 to 41. DOI 10.14341/probl201662237-41.
The report describes 80 men: clomiphene 30, hCG 10, hCG plus recombinant FSH 30, and self-selected no-treatment control 10. At six months, conception was 6/30 in the clomiphene group and oligo-teratozoospermia reportedly resolved in 19/30; three deteriorated.
- Participants / model
- 80 men with pathospermia and infertility; treatment selection and control participation were not randomized
- Treatment
- Clomiphene, hCG, hCG plus recombinant FSH, or observation
- Follow-up
- 3 months with continuation to 6 months
- Study design
- Prospective comparative study with stratification among treated groups and self-selected untreated controls
There was no randomized placebo comparison, controls self-selected, partner factors confound conception, treatment groups differed, and the study was not powered for safety.
Read the original sourceBangladesh placebo RCT · semen outcomes
Randomized double-blind placebo-controlled trial
Hossain MJ, et al. Clinical and Experimental Reproductive Medicine. 2025. PMID 40899280. DOI 10.5653/cerm.2024.07353.
Among 46 analyzed men, clomiphene improved sperm concentration 9.17→13.88 million/mL, progressive motility 14.67%→21.42%, total motile count 3.53→7.81 million, and testosterone 372→806 ng/dL. Nausea occurred in two and dizziness in three.
- Participants / model
- 50 eugonadal men with idiopathic oligoasthenozoospermia randomized; 46 analyzed
- Treatment
- Clomiphene citrate versus placebo
- Follow-up
- 12 weeks
- Study design
- Single-center randomized double-blind placebo-controlled trial
No pregnancy or live-birth endpoint. The trial was registered after completion; funding was not stated and no relevant conflict was reported.
Read the original sourceChinese abstract · clomiphene versus letrozole with co-treatment
Chinese randomized comparative clinical study
王鑫, 张丛轶, 王静, 李静, 李娅. 转化医学杂志. 2025;14:156 to 160.
The native and publisher-translated abstracts report 206 women randomized 103 per group. Both groups received compound Xuanju capsules; letrozole versus clomiphene had higher reported ovulation (72.82% versus 59.22%) and pregnancy (45.63% versus 31.07%) over three cycles.
- Participants / model
- 206 women with ovulatory-disorder infertility
- Treatment
- Compound Xuanju plus clomiphene versus compound Xuanju plus letrozole
- Follow-up
- Three treatment cycles
- Study design
- Randomized-number-table comparative study reported in abstract
Shared herbal co-treatment, unclear blinding, no live-birth endpoint, and abstract-only reporting limit inference.
Read the original sourceWHO male-infertility trial · no efficacy
Randomized double-blind placebo-controlled multicenter trial
World Health Organization. International Journal of Andrology. 1992. PMID 1516979.
Among 190 couples, six months of male clomiphene did not improve semen quality. Eight-month cumulative pregnancy was 8.1% with clomiphene versus 11.7% with placebo.
- Participants / model
- 190 couples with idiopathic male semen-quality impairment and no major untreated female-factor infertility
- Treatment
- Oral clomiphene citrate versus placebo to male partners
- Follow-up
- 6 months of treatment; pregnancy assessed through 8 months
- Study design
- Multicenter randomized double-blind placebo-controlled trial
The trial studied idiopathic male infertility, not biochemically confirmed secondary hypogonadism; pregnancy is a couple-level outcome.
Read the original sourcePCOS infertility · letrozole outperformed clomiphene
Randomized double-blind multicenter trial
Richard S. Legro, Robert G. Brzyski, Michael P. Diamond, et al.; NICHD Reproductive Medicine Network. New England Journal of Medicine. 2014. PMID 25006718.
Live birth was 103/374 (27.5%) with letrozole and 72/376 (19.1%) with clomiphene (rate ratio 1.44, 95% CI 1.10 to 1.87; p=0.007). Ovulation was 61.7% versus 48.3% of cycles. Twin pregnancy was 3.4% versus 7.4%, without a significant difference.
- Participants / model
- 750 infertile women aged 18 to 40 with polycystic ovary syndrome and defined reproductive eligibility
- Treatment
- Letrozole versus clomiphene
- Follow-up
- Up to five treatment cycles with pregnancy follow-up
- Study design
- Randomized double-blind multicenter comparative trial
- Funding
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
PCOS eligibility included reproductive anatomy and partner semen criteria. The study was underpowered for twins and congenital anomalies; 73.1% of infants received the planned registry physical examination.
Read the original sourceDoes clomiphene make post-cycle therapy proven?
Three clinical reports suggest earlier hormone or semen recovery during clomiphene-containing care, but none isolates clomiphene. Natural recovery, treatment choice, hCG, short testosterone bridging, aromatase inhibitors, FSH, different AAS histories, and clinical follow-up all affect the result.
| Study | Design | Result | Limit |
|---|---|---|---|
| Al Hashimi 2022 | 520 AAS users observed for three months; 463 then chose individualized treatment and 57 observation | Treated men recovered hormones, IIEF, testicular size, and semen faster; 14 pregnancies among 94 infertility presentations by month 12 | The paper calls the study randomized, but groups followed patient choice; treatment also used hCG, tamoxifen, aromatase inhibitor, or FSH |
| Henriksen 2024 pilot | 81 screened, 17 eligible, 10 completed; all received clomiphene, six had a testosterone bridge, seven received indicated hCG | Five of 10 reached or ended within the normal testosterone range; no serious adverse event | Open feasibility study; symptoms did not track testosterone response; heavy selection and mixed treatment |
| İbis 2025/2026 cohort | 79 short-term AAS users managed with observation, clomiphene, or clomiphene plus hCG | All groups normalized hormones by month 6; 12-month normozoospermia 69.2%, 87.5%, and 58.6% | Retrospective and nonrandomized; no pregnancy or live-birth endpoint |
These studies describe supervised research care. They do not define a self-directed protocol.
Al Hashimi et al. · chosen mixed-treatment AAS cohort
Prospective nonrandomized comparative cohort
Al Hashimi M, et al. Andrologia. 2022. PMID 36065528. DOI 10.1111/and.14576.
After three months of observation, 463 of 520 former AAS users chose individualized treatment and 57 continued observation. Treated men recovered hormones, sexual function, testicular size, and semen earlier; 14 pregnancies were reported among 94 infertility presentations by month 12.
- Participants / model
- 520 men after anabolic-androgenic steroid use
- Treatment
- Individualized hCG plus clomiphene, sometimes with tamoxifen, aromatase inhibitor, or FSH, versus observation
- Follow-up
- Up to 12 months after an initial 3-month observation period
- Study design
- Prospective cohort assigned by patient choice despite the paper's randomized label
No clomiphene-only arm. Baseline and treatment-selection confounding are severe. The paper inconsistently reports 74 versus 94 infertility cases. The authors reported no conflicts.
Read the original sourceHenriksen et al. · mixed-intervention pilot
Open uncontrolled feasibility pilot
Henriksen HCB, et al. Performance Enhancement & Health. 2024;12(3):100283. DOI 10.1016/j.peh.2024.100283.
Of 81 screened and 17 eligible men, 10 completed. Five reached or ended within the normal testosterone range; withdrawal symptoms did not track testosterone response. Seven reported some clomiphene adverse effect at week 4, falling to three at week 16; no serious adverse event.
- Participants / model
- Men with long-term AAS use in substance-use-disorder care; 10 completers
- Treatment
- Clomiphene for all; six also received a short testosterone bridge and seven indicated hCG
- Follow-up
- 16 weeks
- Study design
- Open uncontrolled feasibility pilot with mixed interventions
- Funding
- Public Norwegian and Oslo University Hospital support
Severe screening selection, co-treatment, clinical care, and time prevent clomiphene-only attribution.
Read the original sourceİbis et al. · nonrandomized PCT cohort
Retrospective dual-center comparative cohort
İbis MA, et al. BJU International. Epub 2025. PMID 41147237. DOI 10.1111/bju.70059.
In 79 men, clomiphene-containing groups recovered hormones and semen earlier. All groups normalized hormones by month 6; at month 12 normozoospermia was 69.2% clomiphene, 87.5% clomiphene plus hCG, and 58.6% untreated.
- Participants / model
- 79 recreational bodybuilders after no more than 6 months of AAS use with documented normal pre-cycle hormones and semen
- Treatment
- Observation, clomiphene, or clomiphene plus hCG; FSH suggested for five men
- Follow-up
- 12 months
- Study design
- Retrospective nonrandomized dual-center cohort
Natural recovery was substantial, treatment was not randomized, adjusted estimates were imprecise, and there was no pregnancy or live-birth endpoint. Adverse-event and funding details remain unresolved.
Read the original sourceDoes clomiphene improve muscle or performance in healthy men?
No controlled trial in the cited evidence measured hypertrophy, maximal strength, power, endurance, training adaptation, or recovery in healthy eugonadal athletes. The 2.2 kg lean-mass increase came from obese symptomatic men with low testosterone and lasted 12 weeks. It did not establish better performance.
Enclomiphene is the isolated trans isomer. Clomid is a mixture of enclomiphene and zuclomiphene, so enclomiphene-only trials need their own label.
78 men · hormones and body-composition surrogates
Randomized double-blind placebo-controlled trial
Andressa Heimbecher Soares, Nidia Celeste Horie, Lucas Augusto Piccinin Chiang, et al. International Journal of Obesity. 2018. PMID 29777228.
Seventy-eight men were randomized and 67 analyzed at 12 weeks. Hormones and several lean-mass measures rose; BMI, waist, fat mass, endothelial function, and most sexual complaints were unchanged, and HDL fell. No clomiphene participant discontinued for an adverse event.
- Participants / model
- 78 men with obesity-associated secondary hypogonadism randomized; 67 analyzed at 12 weeks
- Treatment
- Oral clomiphene citrate versus placebo
- Follow-up
- 12 weeks
- Study design
- Single-center randomized double-blind placebo-controlled trial
Short single-center surrogate trial without a testosterone-replacement comparator, fertility endpoints, long-term symptoms, or cardiovascular outcomes; diet and activity were not standardized.
Read the original sourceUS label · female ovulatory dysfunction and major warnings
FDA prescribing information
Cosette Pharmaceuticals, Inc. CLOMIPHENE CITRATE tablets. DailyMed setid 2ca373c1-4dba-4126-8616-5c533d606fe5. Updated January 31, 2025.
The US label covers ovulatory dysfunction in women desiring pregnancy, describes the mixed cis/trans isomer product, and warns about visual disorders, ovarian hyperstimulation, multiple pregnancy, liver disease, hypertriglyceridemia/pancreatitis, and prolonged isomer persistence. It says adequate controlled male-infertility efficacy evidence is absent.
- Participants / model
- Women with ovulatory dysfunction who desire pregnancy; label discussion also addresses unsupported male use
- Treatment
- Oral clomiphene citrate tablets
- Follow-up
- Current product record; treatment is cycle-limited in the label
- Study design
- Regulatory prescribing information
The label is not a male-hypogonadism or bodybuilding approval and does not provide a universal clomiphene half-life because the isomers persist differently.
Read the original sourceDoes clomiphene have one reliable half-life?
Clomiphene is an isomer mixture, and the cis isomer zuclomiphene persists much longer than the trans isomer. The label reports prolonged radiolabeled material and detectable zuclomiphene beyond a month, so one parent-drug half-life would be misleading.
US label · female ovulatory dysfunction and major warnings
FDA prescribing information
Cosette Pharmaceuticals, Inc. CLOMIPHENE CITRATE tablets. DailyMed setid 2ca373c1-4dba-4126-8616-5c533d606fe5. Updated January 31, 2025.
The US label covers ovulatory dysfunction in women desiring pregnancy, describes the mixed cis/trans isomer product, and warns about visual disorders, ovarian hyperstimulation, multiple pregnancy, liver disease, hypertriglyceridemia/pancreatitis, and prolonged isomer persistence. It says adequate controlled male-infertility efficacy evidence is absent.
- Participants / model
- Women with ovulatory dysfunction who desire pregnancy; label discussion also addresses unsupported male use
- Treatment
- Oral clomiphene citrate tablets
- Follow-up
- Current product record; treatment is cycle-limited in the label
- Study design
- Regulatory prescribing information
The label is not a male-hypogonadism or bodybuilding approval and does not provide a universal clomiphene half-life because the isomers persist differently.
Read the original sourceWhich warnings matter before anyone calls it a harmless SERM?
The label warns about visual injury, ovarian hyperstimulation, multiple pregnancy, liver disease, high triglycerides, pancreatitis, and thrombotic events. Male studies report rising estradiol, breast tenderness, mood change, blurred vision, dizziness, fatigue, headache, and gastrointestinal symptoms. Most cohorts are too short or too selected to estimate uncommon or long-term harm.
The 400-man series' 8% side-effect figure came from 120 men who remained treated beyond three years. In Huijben, adverse-event documentation was missing in 130 of 153 charts.
A VA database study matched 2,518 clomiphene users to 2,518 testosterone users and found fewer coded events with clomiphene. Infertility remained coded in 895 versus 41, while smoking, severity, symptoms, free testosterone, bone density, and medication differences were unresolved. Mortality was 1.83% versus 10.13%; the design cannot make that a treatment effect.
US label · female ovulatory dysfunction and major warnings
FDA prescribing information
Cosette Pharmaceuticals, Inc. CLOMIPHENE CITRATE tablets. DailyMed setid 2ca373c1-4dba-4126-8616-5c533d606fe5. Updated January 31, 2025.
The US label covers ovulatory dysfunction in women desiring pregnancy, describes the mixed cis/trans isomer product, and warns about visual disorders, ovarian hyperstimulation, multiple pregnancy, liver disease, hypertriglyceridemia/pancreatitis, and prolonged isomer persistence. It says adequate controlled male-infertility efficacy evidence is absent.
- Participants / model
- Women with ovulatory dysfunction who desire pregnancy; label discussion also addresses unsupported male use
- Treatment
- Oral clomiphene citrate tablets
- Follow-up
- Current product record; treatment is cycle-limited in the label
- Study design
- Regulatory prescribing information
The label is not a male-hypogonadism or bodybuilding approval and does not provide a universal clomiphene half-life because the isomers persist differently.
Read the original sourceKrzastek et al. · 400-man retrospective cohort
Retrospective two-center cohort
Krzastek SC, Sharma D, Abdullah N, et al. Journal of Urology. 2019;202(5):1029-1035. PMID 31216250. DOI 10.1097/JU.0000000000000396.
Of 400 treated men, 120 remained treated beyond three years; in that selected group 88% were eugonadal, 77% reported symptom improvement, and 8% reported side effects.
- Participants / model
- 400 men treated for hypogonadism; 120 treated longer than three years
- Treatment
- Clomiphene citrate
- Follow-up
- Mean 25.5 months; selected subgroup beyond 3 years
- Study design
- Retrospective two-center cohort
No untreated control and strong survivor or continuation selection.
Read the original sourceHuijben et al. · response, withdrawal, and chart gaps
Retrospective cohort
Huijben M, Huijsmans RLN, Lock MTWT, de Kemp VF, de Kort LMO, van Breda JHMK. Endocrinology, Diabetes & Metabolism. 2023;6:e416. PMID 36998229.
Mean testosterone rose 9→16 nmol/L and 74% reported improvement. Testosterone fell after 48/52 withdrawal trials. Recorded adverse events occurred in 16/153, but adverse-event documentation was absent in 130 charts.
- Participants / model
- 153 heterogeneous men treated for hypogonadism
- Treatment
- Clomiphene citrate
- Follow-up
- Retrospective follow-up with variable duration and withdrawal trials
- Study design
- Single-center retrospective cohort
No validated symptom tool or control. At endpoint only 43 remained followed; 26 were lost, 71 stopped, and 14 switched to testosterone. Authors reported no funding or conflicts.
Read the original sourceVA cohort · comparative associations
Matched retrospective database cohort
Testosterone Versus Clomiphene Treatment of Hypogonadism: A Retrospective Analysis in US Veterans. Andrology. 2026. PMID 42015850. DOI 10.1111/andr.70229.
2,518 clomiphene users were matched to 2,518 testosterone users. Coded cardiovascular, polycythemia, osteoporosis, and mortality outcomes were lower with clomiphene; mortality was 1.83% versus 10.13%.
- Participants / model
- 5,036 matched US veterans treated for hypogonadism
- Treatment
- Clomiphene citrate versus testosterone
- Follow-up
- Mean follow-up about 3.4 to 3.8 years
- Study design
- Retrospective administrative-database comparison
Infertility remained profoundly imbalanced (895 vs 41), and smoking, severity, medicines, symptoms, free testosterone, and bone density were omitted. The mortality contrast is not causal. Authors reported no funding or conflicts.
Read the original source78 men · hormones and body-composition surrogates
Randomized double-blind placebo-controlled trial
Andressa Heimbecher Soares, Nidia Celeste Horie, Lucas Augusto Piccinin Chiang, et al. International Journal of Obesity. 2018. PMID 29777228.
Seventy-eight men were randomized and 67 analyzed at 12 weeks. Hormones and several lean-mass measures rose; BMI, waist, fat mass, endothelial function, and most sexual complaints were unchanged, and HDL fell. No clomiphene participant discontinued for an adverse event.
- Participants / model
- 78 men with obesity-associated secondary hypogonadism randomized; 67 analyzed at 12 weeks
- Treatment
- Oral clomiphene citrate versus placebo
- Follow-up
- 12 weeks
- Study design
- Single-center randomized double-blind placebo-controlled trial
Short single-center surrogate trial without a testosterone-replacement comparator, fertility endpoints, long-term symptoms, or cardiovascular outcomes; diet and activity were not standardized.
Read the original sourceStudies and sources
US label · female ovulatory dysfunction and major warnings
FDA prescribing information
Cosette Pharmaceuticals, Inc. CLOMIPHENE CITRATE tablets. DailyMed setid 2ca373c1-4dba-4126-8616-5c533d606fe5. Updated January 31, 2025.
The US label covers ovulatory dysfunction in women desiring pregnancy, describes the mixed cis/trans isomer product, and warns about visual disorders, ovarian hyperstimulation, multiple pregnancy, liver disease, hypertriglyceridemia/pancreatitis, and prolonged isomer persistence. It says adequate controlled male-infertility efficacy evidence is absent.
- Participants / model
- Women with ovulatory dysfunction who desire pregnancy; label discussion also addresses unsupported male use
- Treatment
- Oral clomiphene citrate tablets
- Follow-up
- Current product record; treatment is cycle-limited in the label
- Study design
- Regulatory prescribing information
The label is not a male-hypogonadism or bodybuilding approval and does not provide a universal clomiphene half-life because the isomers persist differently.
Read the original sourcePCOS infertility · 626 participants and live birth
Randomized double-blind multicenter trial
Richard S. Legro, Huiman X. Barnhart, William D. Schlaff, et al.; Cooperative Multicenter Reproductive Medicine Network. New England Journal of Medicine. 2007. PMID 17287476.
Live birth was 47/209 (22.5%) with clomiphene, 15/208 (7.2%) with metformin, and 56/209 (26.8%) with both; combination versus clomiphene was p=0.31. Dropout was 26.3%, 34.6%, and 23.4%, respectively.
- Participants / model
- 626 infertile women with polycystic ovary syndrome
- Treatment
- Clomiphene, extended-release metformin, or both
- Follow-up
- Up to 6 months, then pregnancy follow-up
- Study design
- Randomized double-blind multicenter comparative trial
- Funding
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
No ultrasound follicle monitoring, hCG trigger, or intrauterine insemination was used. Multiple-pregnancy percentages use pregnancies as denominator; serious events were mostly pregnancy complications.
Read the original sourcePCOS infertility · letrozole outperformed clomiphene
Randomized double-blind multicenter trial
Richard S. Legro, Robert G. Brzyski, Michael P. Diamond, et al.; NICHD Reproductive Medicine Network. New England Journal of Medicine. 2014. PMID 25006718.
Live birth was 103/374 (27.5%) with letrozole and 72/376 (19.1%) with clomiphene (rate ratio 1.44, 95% CI 1.10 to 1.87; p=0.007). Ovulation was 61.7% versus 48.3% of cycles. Twin pregnancy was 3.4% versus 7.4%, without a significant difference.
- Participants / model
- 750 infertile women aged 18 to 40 with polycystic ovary syndrome and defined reproductive eligibility
- Treatment
- Letrozole versus clomiphene
- Follow-up
- Up to five treatment cycles with pregnancy follow-up
- Study design
- Randomized double-blind multicenter comparative trial
- Funding
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
PCOS eligibility included reproductive anatomy and partner semen criteria. The study was underpowered for twins and congenital anomalies; 73.1% of infants received the planned registry physical examination.
Read the original sourceWHO male-infertility trial · no efficacy
Randomized double-blind placebo-controlled multicenter trial
World Health Organization. International Journal of Andrology. 1992. PMID 1516979.
Among 190 couples, six months of male clomiphene did not improve semen quality. Eight-month cumulative pregnancy was 8.1% with clomiphene versus 11.7% with placebo.
- Participants / model
- 190 couples with idiopathic male semen-quality impairment and no major untreated female-factor infertility
- Treatment
- Oral clomiphene citrate versus placebo to male partners
- Follow-up
- 6 months of treatment; pregnancy assessed through 8 months
- Study design
- Multicenter randomized double-blind placebo-controlled trial
The trial studied idiopathic male infertility, not biochemically confirmed secondary hypogonadism; pregnancy is a couple-level outcome.
Read the original source78 men · hormones and body-composition surrogates
Randomized double-blind placebo-controlled trial
Andressa Heimbecher Soares, Nidia Celeste Horie, Lucas Augusto Piccinin Chiang, et al. International Journal of Obesity. 2018. PMID 29777228.
Seventy-eight men were randomized and 67 analyzed at 12 weeks. Hormones and several lean-mass measures rose; BMI, waist, fat mass, endothelial function, and most sexual complaints were unchanged, and HDL fell. No clomiphene participant discontinued for an adverse event.
- Participants / model
- 78 men with obesity-associated secondary hypogonadism randomized; 67 analyzed at 12 weeks
- Treatment
- Oral clomiphene citrate versus placebo
- Follow-up
- 12 weeks
- Study design
- Single-center randomized double-blind placebo-controlled trial
Short single-center surrogate trial without a testosterone-replacement comparator, fertility endpoints, long-term symptoms, or cardiovascular outcomes; diet and activity were not standardized.
Read the original sourceRussian report · nonrandomized male-infertility comparison
Russian prospective clinical comparative study
N. S. Kravtsova, R. V. Rozhivanov, and D. G. Kurbatov. Проблемы эндокринологии. 2016;62(2):37 to 41. DOI 10.14341/probl201662237-41.
The report describes 80 men: clomiphene 30, hCG 10, hCG plus recombinant FSH 30, and self-selected no-treatment control 10. At six months, conception was 6/30 in the clomiphene group and oligo-teratozoospermia reportedly resolved in 19/30; three deteriorated.
- Participants / model
- 80 men with pathospermia and infertility; treatment selection and control participation were not randomized
- Treatment
- Clomiphene, hCG, hCG plus recombinant FSH, or observation
- Follow-up
- 3 months with continuation to 6 months
- Study design
- Prospective comparative study with stratification among treated groups and self-selected untreated controls
There was no randomized placebo comparison, controls self-selected, partner factors confound conception, treatment groups differed, and the study was not powered for safety.
Read the original sourceChinese abstract · clomiphene versus letrozole with co-treatment
Chinese randomized comparative clinical study
王鑫, 张丛轶, 王静, 李静, 李娅. 转化医学杂志. 2025;14:156 to 160.
The native and publisher-translated abstracts report 206 women randomized 103 per group. Both groups received compound Xuanju capsules; letrozole versus clomiphene had higher reported ovulation (72.82% versus 59.22%) and pregnancy (45.63% versus 31.07%) over three cycles.
- Participants / model
- 206 women with ovulatory-disorder infertility
- Treatment
- Compound Xuanju plus clomiphene versus compound Xuanju plus letrozole
- Follow-up
- Three treatment cycles
- Study design
- Randomized-number-table comparative study reported in abstract
Shared herbal co-treatment, unclear blinding, no live-birth endpoint, and abstract-only reporting limit inference.
Read the original sourcePubChem CID 2800 · clomiphene base identity
Government substance database
National Library of Medicine. PubChem Compound Summary for CID 2800, Clomiphene.
Identifies clomiphene base as C26H28ClNO, molecular weight 406.0 g/mol, CID 2800.
- Participants / model
- Not applicable
- Treatment
- Not applicable
- Follow-up
- Living database record
- Study design
- Curated chemical identity record
The marketed citrate salt is a mixed-isomer product and has a different formula and molecular weight from the base record.
Read the original sourceDadhich et al. · chosen-treatment symptom cohort
Prospective nonrandomized comparative cohort
Dadhich P, Ramasamy R, Scovell J, Wilken N, Lipshultz L. Indian Journal of Urology. 2017;33(3):236-240. PMID 28717276. DOI 10.4103/iju.IJU_372_16.
Among 23 men choosing clomiphene, testosterone rose 235→438 ng/dL and overall ADAM/qADAM scores improved, while the libido item worsened 3.75→3.2 (p=.04).
- Participants / model
- 75 symptomatic men; 23 chose clomiphene and 52 chose testosterone
- Treatment
- Patient-chosen clomiphene or testosterone therapy
- Follow-up
- Prospective follow-up; duration differed between groups
- Study design
- Nonrandomized prospective comparative cohort
Clomiphene users were younger and fertility-motivated; treatment choice and unequal follow-up confound comparison. The authors reported no funding or conflicts.
Read the original sourceHabous et al. · clomiphene vs hCG vs combination
Randomized active-comparator trial
Habous M, Giona S, Tealab A, et al. BJU International. 2018;122(5):889-897. PMID 29772111. DOI 10.1111/bju.14401.
The abstract reports testosterone and qADAM improvement in clomiphene, hCG, and combination arms, with the largest qADAM gain in the combination arm.
- Participants / model
- Men with hypogonadism; abstract reports total n=282 while listed group counts sum to 283
- Treatment
- Clomiphene, hCG, or both
- Follow-up
- 3 months
- Study design
- Randomized active-comparator study without placebo
No semen or pregnancy endpoint. The abstract does not resolve the adverse-event, funding, or denominator details.
Read the original sourceKrzastek et al. · 400-man retrospective cohort
Retrospective two-center cohort
Krzastek SC, Sharma D, Abdullah N, et al. Journal of Urology. 2019;202(5):1029-1035. PMID 31216250. DOI 10.1097/JU.0000000000000396.
Of 400 treated men, 120 remained treated beyond three years; in that selected group 88% were eugonadal, 77% reported symptom improvement, and 8% reported side effects.
- Participants / model
- 400 men treated for hypogonadism; 120 treated longer than three years
- Treatment
- Clomiphene citrate
- Follow-up
- Mean 25.5 months; selected subgroup beyond 3 years
- Study design
- Retrospective two-center cohort
No untreated control and strong survivor or continuation selection.
Read the original sourceHuijben et al. · response, withdrawal, and chart gaps
Retrospective cohort
Huijben M, Huijsmans RLN, Lock MTWT, de Kemp VF, de Kort LMO, van Breda JHMK. Endocrinology, Diabetes & Metabolism. 2023;6:e416. PMID 36998229.
Mean testosterone rose 9→16 nmol/L and 74% reported improvement. Testosterone fell after 48/52 withdrawal trials. Recorded adverse events occurred in 16/153, but adverse-event documentation was absent in 130 charts.
- Participants / model
- 153 heterogeneous men treated for hypogonadism
- Treatment
- Clomiphene citrate
- Follow-up
- Retrospective follow-up with variable duration and withdrawal trials
- Study design
- Single-center retrospective cohort
No validated symptom tool or control. At endpoint only 43 remained followed; 26 were lost, 71 stopped, and 14 switched to testosterone. Authors reported no funding or conflicts.
Read the original sourceAnno et al. · one-year AMS cohort
Retrospective cohort
Anno Y, et al. International Journal of Urology. 2026. PMID 41250569. DOI 10.1111/iju.70289.
In 54 symptomatic Japanese men, testosterone and total Aging Males' Symptoms score improved over one year, while the sexual-dysfunction domain did not.
- Participants / model
- 54 Japanese men with late-onset hypogonadism symptoms
- Treatment
- Clomiphene citrate
- Follow-up
- 1 year
- Study design
- Retrospective uncontrolled cohort
- Funding
- PubMed record lists no grants; authors reported no conflict
The abstract does not report absolute outcome values or full adverse-event detail.
Read the original sourceKim et al. · stricter biochemical response cohort
Retrospective response-predictor cohort
Kim JK, et al. Journal of Sexual Medicine. 2026. PMID 42251758. DOI 10.1093/jsxmed/qdag159.
136/292 men (47%) reached testosterone ≥400 ng/dL plus a ≥200-ng/dL rise within 12 weeks. Higher baseline LH predicted lower response odds, and prior androgen-deprivation therapy had OR 0.11.
- Participants / model
- 292 men with low or borderline testosterone plus symptoms or objective signs
- Treatment
- Clomiphene citrate
- Follow-up
- Response assessed within 12 weeks
- Study design
- Retrospective clinical cohort
- Funding
- NIH/NCI core support listed; no declared conflict
No symptom outcomes and short follow-up; the response definition is stricter than simple normalization.
Read the original sourceVA cohort · comparative associations
Matched retrospective database cohort
Testosterone Versus Clomiphene Treatment of Hypogonadism: A Retrospective Analysis in US Veterans. Andrology. 2026. PMID 42015850. DOI 10.1111/andr.70229.
2,518 clomiphene users were matched to 2,518 testosterone users. Coded cardiovascular, polycythemia, osteoporosis, and mortality outcomes were lower with clomiphene; mortality was 1.83% versus 10.13%.
- Participants / model
- 5,036 matched US veterans treated for hypogonadism
- Treatment
- Clomiphene citrate versus testosterone
- Follow-up
- Mean follow-up about 3.4 to 3.8 years
- Study design
- Retrospective administrative-database comparison
Infertility remained profoundly imbalanced (895 vs 41), and smoking, severity, medicines, symptoms, free testosterone, and bone density were omitted. The mortality contrast is not causal. Authors reported no funding or conflicts.
Read the original sourceBangladesh placebo RCT · semen outcomes
Randomized double-blind placebo-controlled trial
Hossain MJ, et al. Clinical and Experimental Reproductive Medicine. 2025. PMID 40899280. DOI 10.5653/cerm.2024.07353.
Among 46 analyzed men, clomiphene improved sperm concentration 9.17→13.88 million/mL, progressive motility 14.67%→21.42%, total motile count 3.53→7.81 million, and testosterone 372→806 ng/dL. Nausea occurred in two and dizziness in three.
- Participants / model
- 50 eugonadal men with idiopathic oligoasthenozoospermia randomized; 46 analyzed
- Treatment
- Clomiphene citrate versus placebo
- Follow-up
- 12 weeks
- Study design
- Single-center randomized double-blind placebo-controlled trial
No pregnancy or live-birth endpoint. The trial was registered after completion; funding was not stated and no relevant conflict was reported.
Read the original sourcePozzi et al. · 166-man sperm-response cohort
Retrospective cohort
Pozzi E, De Luca S, Birolini G, et al. World Journal of Men's Health. 2026. PMID 42533482. DOI 10.5534/wjmh.250371.
151/166 reached testosterone ≥3.5 ng/mL. Median sperm concentration rose 4.0→5.6 million/mL; 118 improved and 48 worsened by a median 3.3 million/mL.
- Participants / model
- 166 hypogonadal oligospermic men
- Treatment
- Clomiphene citrate
- Follow-up
- At least 3 months; median follow-up 4 months
- Study design
- Single-center retrospective cohort
No comparator or pregnancy outcome, 11% dropout, exclusion of adverse-event discontinuations, and a white-European cohort limit inference. The authors reported no disclosure.
Read the original sourceGhanem et al. · clomiphene plus vitamin E
Randomized placebo-controlled combination trial
Ghanem H, Shaeer O, El-Segini A. Fertility and Sterility. 2010;93(7):2232-2235. PMID 19268928.
Pregnancy occurred in 11/30 couples assigned clomiphene plus vitamin E and 4/30 assigned placebo; OR 3.76 (95% CI 1.03 to 13.64).
- Participants / model
- 60 men with idiopathic infertility and their partners
- Treatment
- Clomiphene plus vitamin E versus placebo
- Follow-up
- 6 months
- Study design
- Randomized controlled combination-treatment trial
Vitamin E prevents attribution to clomiphene alone, and the confidence interval is wide.
Read the original sourceAl Hashimi et al. · chosen mixed-treatment AAS cohort
Prospective nonrandomized comparative cohort
Al Hashimi M, et al. Andrologia. 2022. PMID 36065528. DOI 10.1111/and.14576.
After three months of observation, 463 of 520 former AAS users chose individualized treatment and 57 continued observation. Treated men recovered hormones, sexual function, testicular size, and semen earlier; 14 pregnancies were reported among 94 infertility presentations by month 12.
- Participants / model
- 520 men after anabolic-androgenic steroid use
- Treatment
- Individualized hCG plus clomiphene, sometimes with tamoxifen, aromatase inhibitor, or FSH, versus observation
- Follow-up
- Up to 12 months after an initial 3-month observation period
- Study design
- Prospective cohort assigned by patient choice despite the paper's randomized label
No clomiphene-only arm. Baseline and treatment-selection confounding are severe. The paper inconsistently reports 74 versus 94 infertility cases. The authors reported no conflicts.
Read the original sourceHenriksen et al. · mixed-intervention pilot
Open uncontrolled feasibility pilot
Henriksen HCB, et al. Performance Enhancement & Health. 2024;12(3):100283. DOI 10.1016/j.peh.2024.100283.
Of 81 screened and 17 eligible men, 10 completed. Five reached or ended within the normal testosterone range; withdrawal symptoms did not track testosterone response. Seven reported some clomiphene adverse effect at week 4, falling to three at week 16; no serious adverse event.
- Participants / model
- Men with long-term AAS use in substance-use-disorder care; 10 completers
- Treatment
- Clomiphene for all; six also received a short testosterone bridge and seven indicated hCG
- Follow-up
- 16 weeks
- Study design
- Open uncontrolled feasibility pilot with mixed interventions
- Funding
- Public Norwegian and Oslo University Hospital support
Severe screening selection, co-treatment, clinical care, and time prevent clomiphene-only attribution.
Read the original sourceİbis et al. · nonrandomized PCT cohort
Retrospective dual-center comparative cohort
İbis MA, et al. BJU International. Epub 2025. PMID 41147237. DOI 10.1111/bju.70059.
In 79 men, clomiphene-containing groups recovered hormones and semen earlier. All groups normalized hormones by month 6; at month 12 normozoospermia was 69.2% clomiphene, 87.5% clomiphene plus hCG, and 58.6% untreated.
- Participants / model
- 79 recreational bodybuilders after no more than 6 months of AAS use with documented normal pre-cycle hormones and semen
- Treatment
- Observation, clomiphene, or clomiphene plus hCG; FSH suggested for five men
- Follow-up
- 12 months
- Study design
- Retrospective nonrandomized dual-center cohort
Natural recovery was substantial, treatment was not randomized, adjusted estimates were imprecise, and there was no pregnancy or live-birth endpoint. Adverse-event and funding details remain unresolved.
Read the original sourceWhy is Clomiphene in A tier?
A for selected female ovulation induction, where randomized trials measured live birth. For men, clomiphene reliably changes hormones in selected patients, while symptom results are mixed, male-partner pregnancy benefit is unproved, post-AAS studies cannot isolate clomiphene, and no controlled healthy-performance trial was found.