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.
Summary
Definition
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
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
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
Diagnostic tests
1st tests to order
- serum total testosterone
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)
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)
Consultant Endocrinologist
Northern Region Gender Dysphoria Service
Tyne & Wear NHS Foundation Trust
Newcastle upon Tyne
UK
Honorary Reader in Reproductive Endocrinology
Department of Metabolism, Digestion and Reproduction
Imperial College London
UK
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
UK
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
TX
利益声明
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
UK
利益声明
NK declares that she has no competing interests.
Peer reviewer acknowledgements
BMJ Best Practice topics are updated on a rolling basis in line with developments in evidence and guidance. The peer reviewers listed here have reviewed the content at least once during the history of the topic.
Disclosures
Peer reviewer affiliations and disclosures pertain to the time of the review.
参考文献
关键文献
Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018 Aug;200(2):423-32.全文 摘要
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.全文 摘要
Matsumoto AM. Diagnosis and evaluation of hypogonadism. Endocrinol Metab Clin North Am. 2022 Mar;51(1):47-62. 摘要
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.全文 摘要
参考文献
A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.
鉴别诊断
- Klinefelter syndrome
- Pituitary macroadenoma
- Prolactinoma
更多 鉴别诊断指南
- Hormones and aging: an Endocrine Society scientific statement
- Evaluation and management of testosterone deficiency: AUA guideline
更多 指南患者教育信息
Erection problems
Fertility problems: some reasons
更多 患者教育信息
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