Letrozole once a week normalizes serum testosterone in obesity-related male hypogonadism
Abstract
Objective: Isolated hypogonadotropic hypogonadism (IHH) is frequently observed in severely obese men, probably as a result of increased estradiol (E 2) production and E 2-mediated negative feedback on pituitary LH secretion. Aromatase inhibitors can reverse this process. This study evaluates whether letrozole once a week can normalize serum testosterone in severely obese men and maintain its long term effect. Design: Open, uncontrolled 6-month pilot study in 12 severely obese men (body mass index>35.0 kg/m 2) with obesity-related IHH and free testosterone levels <225 pmol/l, treated with 2.5 mg letrozole once a week for 6 months. Results: Six weeks of treatment reduced total E 2 from 123±11 to 58±7 pmol/l (P<0.001, mean±s.e.m.), and increased serum LH from 4.4±0.6 to 11.1±1.5 U/l (P<0.001). Total testosterone rose from 5.9±0.5 to 19.6±1.4 nmol/l (P<0.001), and free testosterone from 163±13 to 604±50 pmol/l (P<0.001). Total testosterone rose to within the normal range in all subjects, whereas free testosterone rose to supraphysiological levels in 7 out of 12 men. The testosterone and E 2 levels were stable throughout the week and during the 6-month treatment period. Conclusion: Letrozole 2.5 mg once a week produced a sustained normalization of serum total testosterone in obese men with IHH. However, free testosterone frequently rose to supraphysiological levels. Therefore, a starting dose <2.5 mg once a week is recommended.
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A weekly low dose (2.5 mg) of the aromatase inhibitor letrozole can restore testosterone levels and increase LH levels in severely obese hypogonadal men.
“Accordingly, it has been reported that a weekly low dose (2.5 mg) of the aromatase inhibitor letrozole can restore testosterone levels and increase LH levels in severely obese hypogonadal men (57).”
From Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis (2013) · cites this paper as [57]
Patients with T2DM and insulin resistance show a higher prevalence of hypogonadotropic hypogonadism.
“Accordingly, patients with T2DM and insulin resistance show a higher prevalence of hypogonadotropic hypogonadism (54,55,60)”
From Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis (2013) · cites this paper as [54]
Obesity-related male hypogonadism is considered a form of hypogonadotropic hypogonadism.
“Based on these and other studies (53,54), obesity-related male hypogonadism is now considered as a form of hypogonadotropic hypogonadism (see for a review, references (55,56)).”
From Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis (2013) · cites this paper as [54]
A more recent study also showed a moderate but significant effect of aromatase inhibition on estradiol and testosterone levels in older men.
“A more recent study also showed a moderate but significant effect of aromatase inhibition on estradiol and testosterone levels in older men [37].”
From Aromatase inhibitors in men: effects and therapeutic options (2011) · cites this paper as [37]
In the studies published so far aromatase inhibition in men did not appear to be associated with adverse effects on bone in a number of studies.
“In the studies published so far aromatase inhibition in men did not appear to be associated with adverse effects on bone in a number of studies [37,59,82,83], but in a more recent study a decrease of spine BMD was observed after one year of treatment of elderly men with anastrozole [84].”
From Aromatase inhibitors in men: effects and therapeutic options (2011) · cites this paper as [37]
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- Authors
- Loves, S., Ruinemans-Koerts, J., & de Boer, H.
- Affiliations
- Rijnstate Hospital (NL)
- ORCID
- Loves, Sandra
- Venue
- European Journal of Endocrinology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-05
- Volume
- 158
- Issue
- 5
- Pages
- 741-747
- ISSN
- 0804-4643 (ISSN-L)
- 1479-683X
- OpenAlex
- W2109106905
- Cited by
- 141
- References
- 10
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 11 · 2022: 10 · 2021: 7 · 2020: 2 · 2019: 7 · 2018: 7 · 2017: 16 · 2016: 8 · 2015: 7 · 2014: 6 · 2013: 10 · 2012: 9
- FWCI
- 7.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- letrozole, isolated hypogonadotropic hypogonadism, obesity, male hypogonadism, aromatase inhibitors, estradiol, luteinizing hormone, free testosterone, serum testosterone, weekly dosing, dose optimization
- MeSH terms
- Letrozole, Adult, Estradiol, Humans, Hypogonadism, Male, Middle Aged, Nitriles, Obesity, Sex Hormone-Binding Globulin, Testosterone, Triazoles, Aromatase Inhibitors
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