Do men with normal testosterone–oestradiol ratios benefit from letrozole for the treatment of male infertility?

Liu, Shu-Ling; Kuei, Matthew Lau Sie; Saffari, Seyed Ehsan; Zheng, Jiayun; Yeun, Tan Tse; Phoon, Wai Leng, Jessie; Viardot-Foucault, Véronique; Nadarajah, Sadhana; Chan, Jerry Kok Yen; Hao, Tan Heng

doi:10.1016/j.rbmo.2018.09.016

Cited by 26 publications

(13 citation statements)

References 12 publications

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“…(2) The basal T level in the population varies widely, thus the ratio between hormones, such as T/LH or T/E2, was considered as better parameters for male gonad function evaluation [16][17] .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of SARS-CoV-2 infection upon male gonadal function: A single center-based study

Xie

et al. 2020

Preprint

267

256

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medRxiv preprint Funding Information: Health Commission of Hubei Province scientific research project (No. WJ2019Q048 to M.Z.) Conflict of interest:We declare no conflict of interest. Abstract:Since SARS-CoV-2 infection was first identified in December 2019, it spread rapidly and a global pandemic of COVID-19 has occurred. ACE2, the receptor for entry into the target cells by SARS-CoV-2, was found to abundantly express in testes, including spermatogonia, Leydig and Sertoli cells. However, there is no clinical evidence about whether SARS-CoV-2 infection can affect male gonadal function so far.In this study, we compared the sex-related hormones between 81 reproductive-aged men with SARS-CoV-2 infection and 100 age-matched healthy men, and found that serum luteinizing hormone (LH) was significantly increased, but the ratio of testosterone (T) to LH and the ratio of follicle stimulating hormone (FSH) to LH were dramatically decreased in males with COVID-19. Besides, multivariable regression analysis indicated that c-reactive protein (CRP) level was significantly associated with serum T:LH ratio in COVID-19 patients. This study provides the first direct evidence about the influence of medical condition of COVID-19 on male sex hormones, alerting more attention to gonadal function evaluation among patients recovered from SARS-CoV-2 infection, especially the reproductive-aged men.

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Section: Discussionmentioning

confidence: 99%

“…In the early stage of hypogonadism, impaired T production may stimulate the release of LH which can maintain T level temporarily. (2) The basal T level in the population varies widely, thus the ratio between hormones, such as T/LH or T/E2, was considered as better parameters for male gonad function evaluation [16-17] .…”

Section: Discussionmentioning

confidence: 99%

Effect of SARS-CoV-2 infection upon male gonadal function: A single center-based study

Xie

et al. 2020

Preprint

267

256

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“…To reduce estrogen levels and increase sperm production, supplementation of the organotypic culture medium with selective estrogen receptor modulators (SERMs) such as tamoxifen or with aromatase inhibitors such as letrozole could also be considered in future studies. These molecules have indeed proven to be effective in increasing sperm concentration in infertile men [40–42].…”

Section: Discussionmentioning

confidence: 99%

Steroidogenesis and androgen/estrogen signaling pathways are altered inin vitromatured testicular tissues of prepubertal mice

Moutard

Goudin

Jaeger

et al. 2022

Preprint

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Cancer treatments such as chemotherapy can have gonadotoxic effects. In order to preserve and restore the fertility of prepubertal patients with cancer, testicular biopsies are frozen and could theoretically be later matured in vitro to produce spermatozoa for assisted reproductive technology. A complete in vitro spermatogenesis has been obtained from prepubertal testicular tissue in the mouse model, although the sperm yield was low. Since steroid hormones play an essential role in spermatogenesis, it appears necessary to ensure that their synthesis and mechanisms of action are not altered in in vitro cultured tissues. The aim of this study was therefore to investigate steroidogenesis as well as androgen and estrogen signaling during in vitro maturation of mouse prepubertal testicular tissues. Histological, RT-qPCR, Western blot analyses, measurements of cholesterol, steroid hormones levels and aromatase activity were performed on fresh or frozen/thawed in vitro cultured mouse testicular tissues from 6.5 days postpartum (dpp) mice as well as on age-matched in vivo controls. A similar density of Leydig cells (LC) was found after 30 days of organotypic culture (D30) and at 36.5 dpp, the corresponding in vivo time point. However, LC were partially mature after in vitro culture, with decreased Sult1e1 and Insl3 mRNA levels (adult LC markers). Moreover, the transcript levels of Cyp11a1, Cyp17a1 and Hsd17b3 encoding steroidogenic enzymes were decreased in vitro. Increased amounts of progesterone and estradiol and reduced androstenedione intratesticular levels were observed at D30. Furthermore, androgen signaling was altered at D30, with decreased transcript levels of androgen target genes (Rhox5, Septin12). Moreover, the expression and activity of aromatase and estrogen signaling were impaired at D30. The addition of hCG to the organotypic culture medium induced an elevation in androgen production but did not improve sperm yield. In conclusion, this study reports partial LC maturation, disturbed steroidogenic activity of LC, abnormal steroid hormone content as well as altered androgen and estrogen signaling in cultures of fresh and frozen/thawed prepubertal mouse testicular tissues. The organotypic culture system will need to be further improved to increase the efficiency of in vitro spermatogenesis and allow a clinical application.

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“…A few scientific studies also seem to support the therapeutic potential of letrozole in male reproductive health [ 12 ]. Letrozole has been reported to effectively improve sperm parameters in infertile men with low serum testosterone/estradiol levels and increase the chance of successful conception in couples including men with idiopathic severe oligozoospermia [ 13 – 15 ]. However, the potential use of letrozole could be used as a protectant against exposure to harmful reproductive toxicants remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Letrozole protects against cadmium-induced inhibition of spermatogenesis via LHCGR and Hsd3b6 to activate testosterone synthesis in mice

Yao

Wan

Shi

et al. 2022

Reprod Biol Endocrinol

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The heavy metal cadmium is proposed to be one of the environmental endocrine disruptors of spermatogenesis. Cadmium-induced inhibition of spermatogenesis is associated with a hormone secretion disorder. Letrozole is an aromatase inhibitor that increases peripheral androgen levels and stimulates spermatogenesis. However, the potential protective effects of letrozole on cadmium-induced reproductive toxicity remain to be elucidated. In this study, male mice were administered CdCl2 (4 mg/kg BW) orally by gavage alone or in combination with letrozole (0.25 mg/kg BW) for 30 days. Cd exposure caused a significant decreases in body weight, sperm count, motility, vitality, and plasma testosterone levels. Histopathological changes revealed extensive vacuolization and decreased spermatozoa in the lumen. However, in the Cd + letrozole group, letrozole treatment compensated for deficits in sperm parameters (count, motility, and vitality) induced by Cd. Letrozole treatment significantly increased serum testosterone levels, which were reduced by Cd. Histopathological studies revealed a systematic array of all germ cells, a preserved basement membrane and relatively less vacuolization. For a mechanistic examination, RNA-seq was used to profile alterations in gene expression in response to letrozole. Compared with that in the Cd-treated group, RNA-Seq analysis showed that 214 genes were differentially expressed in the presence of letrozole. Gene ontology (GO) enrichment analysis and KEGG signaling pathway analysis showed that steroid biosynthetic processes were the processes most affected by letrozole treatment. Furthermore, we found that the expression of the testosterone synthesis-related genes LHCGR (luteinizing hormone/choriogonadotropin receptor) and Hsd3b6 (3 beta- and steroid delta-isomerase 6) was significantly downregulated in Cd‐treated testes, but these genes maintained similar expression levels in letrozole-treated testes as those in the control group. However, the transcription levels of inflammatory cytokines, such as IL-1β and IL-6, and oxidative stress-related genes (Nrf2, Nqo1, and Ho-1) showed no changes. The present study suggests that the potential protective effect of letrozole on Cd-induced reproductive toxicity might be mediated by the upregulation of LHCGR and Hsd3b6, which would beneficially increase testosterone synthesis to achieve optimum protection of sperm quality and spermatogenesis.

show abstract

Do men with normal testosterone–oestradiol ratios benefit from letrozole for the treatment of male infertility?

Cited by 26 publications

References 12 publications

Effect of SARS-CoV-2 infection upon male gonadal function: A single center-based study

Effect of SARS-CoV-2 infection upon male gonadal function: A single center-based study

Steroidogenesis and androgen/estrogen signaling pathways are altered inin vitromatured testicular tissues of prepubertal mice

Letrozole protects against cadmium-induced inhibition of spermatogenesis via LHCGR and Hsd3b6 to activate testosterone synthesis in mice

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