Evidence map›Paper›PMID 42313386›Full record

Trial reportJAMA network open2026

Letrozole and Infertility Among Males With Spermatogenic Failure: A Randomized Clinical Trial.

Yifan Sun, Chencheng Yao, Gang Liu, Zheng Li, Xiaoyu Yang, Qigui Chen, Zhen Ye, Honggang Li, Xiaowei Qu, Haibin Guo and 20 more

Abstract readRandomized Controlled TrialMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in JAMA network open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

30 authors.

Yifan SunDepartment of Andrology, the Center for Men's Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Chencheng YaoDepartment of Andrology, the Center for Men's Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Gang LiuDepartment of Andrology, The Reproductive Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China.
Zheng LiDepartment of Andrology, The Reproductive Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China.
Xiaoyu YangState Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Qigui ChenDepartment of Andrology, The Reproductive Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China.
Zhen YeCenter for Reproductive Medicine, Wuhan Children's Hospital: Wuhan Women and Children Medical Care Center, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Honggang LiInstitute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Xiaowei QuReproductive Medicine Center, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
Haibin GuoReproductive Medicine Center, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
Jun YangDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Tao WangDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Guoqing LiangObstetrics & Gynecology Hospital of Fudan University, Shanghai Key Lab of Reproduction and Development, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China.
Xiaobin ZhuDepartment of Gynecology and Obstetrics, Reproductive Medical Center, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yichang LuClinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, China.
Weikang ChenDepartment of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Fengbin ZhangDepartment of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Ruhui TianDepartment of Andrology, the Center for Men's Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Erlei ZhiDepartment of Andrology, the Center for Men's Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Huirong ChenDepartment of Andrology, the Center for Men's Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Fujun ZhaoDepartment of Andrology, the Center for Men's Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Furong BaiDepartment of Andrology, the Center for Men's Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Hongfang SunDepartment of Andrology, the Center for Men's Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jianxiong ZhangDepartment of Andrology, the Center for Men's Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xinjie BuTaizhou School of Clinical Medicine, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, Jiangsu, China.
Dewei QianTaizhou School of Clinical Medicine, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, Jiangsu, China.
Sicheng WuClinical Research Unit, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yan QiuClinical Research Unit, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zheng LiDepartment of Andrology, the Center for Men's Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Peng LiDepartment of Andrology, the Center for Men's Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Importance: Spermatogenic failure (SPGF) is a severe form of male infertility with limited evidence-based medical treatment options. Aromatase inhibitors represent a promising therapeutic strategy for SPGF, but high-quality evidence is lacking. Objective: To evaluate the efficacy and safety of letrozole for improving sperm concentration categories in men with SPGF. Design, Setting, and Participants: This multicenter, open-label, assessor-blinded randomized clinical trial was conducted at 10 male infertility centers in China from July 2023 to March 2024. Men with SPGF (nonobstructive azoospermia [NOA], cryptozoospermia, or severe oligozoospermia) were enrolled. Follow-up for the primary outcome was completed in June 2024. Data were analyzed from July 2024 to March 2025. Interventions: Participants were randomized to receive letrozole (2.5 mg daily) plus vitamins C and E or vitamins C and E alone (control group) for 3 months. Main Outcomes and Measures: The primary outcome was World Health Organization Sperm Concentration Categories (WHO-SCC) upgrade rate at 3 months after randomization. The secondary outcomes were WHO-SCC grades, Dutch Society of Obstetrics and Gynecology Total Motile Sperm Count Categories (NVOG-TMSCC) upgrade rate, semen parameters, and reproductive hormone levels. Results: Among 296 participants (mean [SD] age, 30.2 [3.9] years; 218 [73.6%] with NOA; 147 randomized to the letrozole group and 149 to the control group), 247 (83.4%) completed the trial, and all 296 were included in the primary analysis. WHO-SCC upgrade rates were 14.3% (21 of 147 participants) with letrozole vs 5.4% (8 of 149 participants) with control (risk difference, 9.2% [95% CI, 2.5%-15.8%]; P = .01). Participants in the letrozole group had higher odds of achieving a better WHO-SCC grade than those in the control group (common odds ratio, 2.65 [95% CI, 1.28-5.47]; P = .008). The NVOG-TMSCC upgrade rate was also higher with letrozole. Letrozole significantly increased serum gonadotropins and testosterone while decreasing estradiol. There were no significant between-group differences in semen parameters. Decreased libido (18 [12.2%] vs 8 [5.4%]; P = .04) was more frequent with letrozole than with control. Conclusions and Relevance: In this randomized clinical trial of men with spermatogenic failure, letrozole significantly improved sperm concentration categories and was well tolerated, supporting its use as an option to downstage infertility severity and potentially enable less invasive reproductive management. Trial Registration: chictr.org.cn Identifier: ChiCTR2300073861.

Indexed as

Aromatase InhibitorsInfertility, MaleLetrozoleAdultAzoospermiaChinaHumansMaleSpermatogenesisSperm CountTreatment OutcomeAromatase InhibitorsLetrozole

Identifiers

PMID42313386
PMCPMC13280704

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.