Hypogonadism in men

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Last reviewed: 6 Jun 2025

Last updated: 04 Jul 2025

04 Jul 2025

Evidence supports cardiovascular safety of testosterone therapy in men with hypogonadism

High-quality evidence suggests that testosterone therapy does not increase cardiovascular risk in men with hypogonadism.

A large clinical trial (the TRAVERSE trial) reported that testosterone therapy is noninferior to placebo for incidence of major adverse cardiovascular events in men with hypogonadism and preexisting cardiovascular disease, or at high risk for cardiovascular disease.[61] Mean treatment duration was 21.7 months. In addition, systematic reviews and meta-analyses found no evidence that testosterone increases short-term to medium-term cardiovascular risks in men with hypogonadism.[62][63]

These findings led the US Food and Drug Administration (FDA) to update its safety information for all testosterone products, including the removal of a boxed warning stating that testosterone therapy increases the risk of major adverse cardiovascular outcomes.[64] The results of the TRAVERSE trial will be added to the labels of testosterone products in the US. The FDA have, however, added new information about the risk of increased blood pressure to testosterone product labels.

Clinicians should:

Discuss the risks and benefits of testosterone therapy with patients before starting treatment.
Reassure patients that testosterone therapy for hypogonadism will not increase their risk of heart attack or stroke.
Regularly monitor blood pressure in patients taking testosterone therapy.

These changes update prior safety warnings for testosterone products, including a 2014 warning on the reported risks of stroke, heart attack, and death in men taking these products.

Information about the “limitation of use” for age-related low testosterone has been retained.

See Management: approach

Original source of update

Hypogonadism in men may present with reproductive/sexual clinical features (e.g., incomplete pubertal development, subfertility, gynecomastia), as well as nonreproductive features (e.g., fatigue, anemia, osteoporosis, loss of motivation or concentration, irritability, low or labile mood, body image concerns).

Patients may have additional symptoms due to mass effects when hypogonadism is caused by large parasellar lesions (e.g., headache, peripheral visual disturbance), or may have signs or symptoms of other hormone deficiencies.

Early morning fasting serum total testosterone level <300 nanograms/dL on at least two separate occasions in a man with one or more clinical features confers the diagnosis of hypogonadism in most cases.

Measurement of the gonadotropins (luteinizing hormone [LH], follicle-stimulating hormone [FSH]) distinguishes between a primary cause (dysfunction of the testes) and a secondary (also known as central or hypogonadotropic) cause (pituitary or hypothalamic dysfunction).

Management of men with low testosterone due to nongonadal illness (e.g., obesity) is to optimize treatment of the underlying condition.

Testosterone therapy is used to achieve normal physiologic serum testosterone levels, with dose adjustment to maximum effect on relevant clinical features (without causing erythrocytosis).

Definition

Hypogonadism in males is a clinical syndrome that comprises symptoms and/or signs, along with biochemical evidence of testosterone deficiency. It is usually associated with subfertility.[1][2]

The male gonads (testes) have two primary functions: testosterone production (by the Leydig cells) and spermatogenesis (by the spermatogenic and Sertoli cells in the seminiferous tubules). Hypogonadism in men occurs where there is dysfunction in the normal physiologic mechanism of the hypothalamic-pituitary-gonadal axis that results in a decreased ability to carry out either of these functions.

History and exam

Key diagnostic factors

decreased libido
loss of spontaneous morning erections
erectile dysfunction
normocytic anemia
gynecomastia
subfertility
micropenis
small testes
bifid or hypoplastic scrotum
cryptorchidism, especially if bilateral
segmental dysproportion
bitemporal hemianopia
low trauma fractures
loss of height
anosmia

Full details

Other diagnostic factors

decreased energy and fatigue
absent or incomplete puberty
scrotal hypoplasia, hypopigmentation, and absent rugae
decreased muscle mass and strength
loss of axillary and pubic hair
lack of facial hair
poor concentration and memory
depressed or labile mood
sleep disturbance
hot flashes and sweats
tall stature
fine wrinkling of facial skin

Full details

Risk factors

genetic anomaly
type 2 diabetes mellitus
use of alkylating agents, opioids, or glucocorticoids
use of exogenous sex hormones and GnRH analogs
hyperprolactinemia
parasellar tumor or apoplexy of pituitary macroadenoma
testicular damage
infection
varicocele

Full details

Diagnostic tests

1st tests to order

serum total testosterone

Full details

Tests to consider

serum sex hormone-binding globulin (SHBG)
calculated free testosterone
serum LH/FSH
semen analysis
CBC
serum prolactin
serum transferrin saturation and ferritin
MRI pituitary
genetic testing
dual-energy x-ray absorptiometry (DEXA or DXA)

Full details

Treatment algorithm

ONGOING

nongonadal illness

not desiring fertility currently: primary hypogonadism

not desiring fertility currently: secondary hypogonadism

desiring fertility currently: primary hypogonadism

desiring fertility currently: secondary hypogonadism

Contributors

Authors

Richard Quinton, MD FRCP(Edin)

Consultant Endocrinologist

Northern Region Gender Dysphoria Service

Tyne & Wear NHS Foundation Trust

Newcastle upon Tyne

Honorary Reader in Reproductive Endocrinology

Department of Metabolism, Digestion and Reproduction

Imperial College London

Disclosures

RQ has received speaker fees and an advisory board fee from Besins Healthcare UK, speaker fees from Androlabs, and was on an advisory board for Roche Diagnostics. RQ is an author of several references cited in this topic.

Channa N. Jayasena, PhD FRCP FRCPath

Consultant and Reader in Reproductive Endocrinology/Andrology

Department of Investigative Medicine

Hammersmith Hospital

Imperial College London

London

Disclosures

CNJ has an investigator-led research grant from LogixX Pharma Ltd. CNJ is supported by a National Institute for Health Research (NIHR) Post-Doctoral Fellowship. CNJ is an author of several references cited in this topic.

Acknowledgements

Dr Richard Quinton and Dr Channa N. Jayasena would like to gratefully acknowledge Dr Charles Welliver, Dr T. Hugh Jones, Dr Milena Braga-Basaria, and Dr Shehzad Basaria, previous contributors to this topic.

Disclosures

CW has worked as a consultant for Coloplast, and as an investigator for Auxilium Pharmaceuticals, Mereo BioPharma, PROCEPT BioRobotics, and Repros; and he is a paid reviewer at Oakstone Publishing and BMJ Best Practice. CW also has a family member who is an employee at Bristol-Myers Squibb. THJ and SB are authors of references cited in this topic. MB declared that she had no competing interests.

Peer reviewers

Randal J. Urban, MD

Professor

Department of Internal Medicine

University of Texas Medical Branch

Galveston

Disclosures

RJU declares that he has no competing interests.

Niki Karavitaki, MBBS, MSc, PhD

Consultant Endocrinologist

Oxford Centre for Diabetes, Endocrinology and Metabolism

Churchill Hospital

Oxford

Disclosures

NK declares that she has no competing interests.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018 Aug;200(2):423-32.Full text Abstract

Jayasena CN, Anderson RA, Llahana S, et al. Society for Endocrinology guidelines for testosterone replacement therapy in male hypogonadism. Clin Endocrinol (Oxf). 2022 Feb;96(2):200-19.Full text Abstract

Matsumoto AM. Diagnosis and evaluation of hypogonadism. Endocrinol Metab Clin North Am. 2022 Mar;51(1):47-62. Abstract

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 May 1;103(5):1715-44.Full text Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials
- Klinefelter syndrome
- Pituitary macroadenoma
- Prolactinoma
More Differentials
Guidelines
- Hormones and aging: an Endocrine Society scientific statement
- Evaluation and management of testosterone deficiency: AUA guideline
More Guidelines
Patient information
Erection problems
Fertility problems: some reasons
More Patient information
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Hypogonadism in men

​Evidence supports cardiovascular safety of testosterone therapy in men with hypogonadism

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic tests

1st tests to order

Tests to consider

Treatment algorithm

nongonadal illness

not desiring fertility currently: primary hypogonadism

not desiring fertility currently: secondary hypogonadism

desiring fertility currently: primary hypogonadism

desiring fertility currently: secondary hypogonadism

Contributors

Authors

Richard Quinton, MD FRCP(Edin)

Disclosures

Channa N. Jayasena, PhD FRCP FRCPath

Disclosures

Acknowledgements

Disclosures

Peer reviewers

Randal J. Urban, MD

Disclosures

Niki Karavitaki, MBBS, MSc, PhD

Disclosures

References

Key articles

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials

Guidelines

Patient information

Log in or subscribe to access all of BMJ Best Practice

Log in or subscribe to access all of BMJ Best Practice

Log in to access all of BMJ Best Practice

Evidence supports cardiovascular safety of testosterone therapy in men with hypogonadism