HCG (human chorionic gonadotropin) can cause gynaecomastia in males, and this is a recognised adverse effect listed in the prescribing information for licensed HCG products in the UK. By stimulating testosterone production in the testes, HCG indirectly raises oestrogen levels through a process called aromatisation — the conversion of testosterone to oestradiol. When oestrogen rises disproportionately relative to androgens, glandular breast tissue in males can proliferate. This article explains the hormonal mechanism behind HCG-related gynaecomastia, who is most at risk, how to recognise it, and what management options are available under NHS and MHRA guidance.

How HCG Affects Hormone Levels in the Body

HCG mimics LH to stimulate testicular testosterone production; the resulting increase in aromatisation raises oestradiol levels, shifting the oestrogen-to-testosterone ratio in males.

Human chorionic gonadotropin (HCG) is a hormone naturally produced during pregnancy, but it is also used medically in a range of clinical contexts. In men, HCG acts on the Leydig cells of the testes by mimicking luteinising hormone (LH), thereby stimulating the production of testosterone. Licensed indications in males include the treatment of hypogonadotrophic hypogonadism (to stimulate testosterone production and spermatogenesis), prepubertal cryptorchidism, and selected cases of delayed puberty — though specific indications and dosing vary by product, and clinicians should consult the relevant Summary of Product Characteristics (SmPC) and the British National Formulary (BNF) for the product being prescribed. In women, ovulation triggering is typically achieved using choriogonadotropin alfa (for example, Ovitrelle), which is a recombinant form; the licensed indications for urinary and recombinant preparations differ, and the appropriate SmPC should be consulted.

Whilst HCG directly raises testosterone levels in men, it also indirectly increases oestrogen. This occurs because testosterone is converted into oestradiol — a form of oestrogen — through a process called aromatisation, catalysed by the enzyme aromatase found in adipose tissue, the liver, and other organs. When HCG stimulates a significant rise in testosterone, the corresponding increase in aromatisation can lead to elevated oestrogen levels in the bloodstream.

This hormonal shift — where oestrogen rises disproportionately relative to androgens — is the central mechanism by which HCG can disrupt the normal hormonal equilibrium in males. The ratio of oestrogen to testosterone is particularly important in male breast tissue, and any shift in this balance can have physiological consequences, including changes to glandular breast tissue. Understanding this pharmacological pathway is essential to appreciating why gynaecomastia is a recognised potential side effect of HCG therapy.

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The Link Between HCG and Gynaecomastia

Gynaecomastia is a recognised adverse reaction to HCG, caused by elevated oestradiol stimulating oestrogen receptors in male breast tissue, leading to glandular proliferation.

Gynaecomastia refers to the benign enlargement of glandular breast tissue in males, and it is a recognised adverse effect associated with HCG use. The condition arises primarily due to the oestrogen-to-testosterone imbalance described above. When HCG stimulates testicular testosterone production, the subsequent increase in aromatisation can cause oestradiol levels to rise, stimulating oestrogen receptors in breast tissue and leading to glandular proliferation.

Gynaecomastia is listed as an adverse reaction in the prescribing information (SmPCs) for licensed HCG products available in the UK, confirming that this is a pharmacologically plausible and clinically recognised adverse reaction. NICE CKS guidance on gynaecomastia also identifies exogenous hormonal agents, including gonadotrophins, as a recognised cause.

The risk may increase with higher doses or more prolonged courses of HCG, as greater stimulation of testosterone production leads to greater aromatisation; however, robust dose–response data in humans are limited, and this relationship should be understood as a plausible pharmacological inference rather than a firmly established clinical finding. Individuals with higher baseline aromatase activity — such as those with a higher body fat percentage — may be more susceptible. The timing of gynaecomastia onset can vary; some individuals notice breast changes within weeks of starting HCG, whilst others may develop symptoms after longer-term use.

In some cases, the condition may partially or fully resolve after discontinuation of HCG, particularly if identified early before fibrotic changes occur in the glandular tissue. Reversibility is less likely once fibrosis has developed. If breast changes appear atypical or do not follow the expected pattern for HCG-related gynaecomastia, alternative underlying causes should be considered and investigated appropriately.

Who Is Most at Risk of Developing Gynaecomastia

Men with higher body fat, older age, pre-existing hormonal imbalances, or those using HCG alongside anabolic steroids face the greatest risk of HCG-related gynaecomastia.

Not all individuals who use HCG will develop gynaecomastia, and several factors influence individual susceptibility. Understanding these risk factors can help clinicians and patients make informed decisions about treatment and monitoring.

Key risk factors include:

• Higher body fat percentage: Adipose tissue contains aromatase, so individuals with more body fat convert more testosterone to oestradiol, increasing the risk of oestrogen-driven breast tissue changes.

• Older age: Ageing is associated with a relatively lower androgen-to-oestrogen ratio, which may increase susceptibility to oestrogen-driven breast tissue changes.

• Pre-existing hormonal imbalances: Men with conditions such as hypogonadotrophic hypogonadism or liver disease may already have altered oestrogen metabolism, compounding the effects of HCG.

• Concurrent use of anabolic steroids or other hormonal agents: Some individuals use HCG illicitly alongside anabolic steroids — a practice sometimes seen in bodybuilding that is both unsafe and, in many circumstances, illegal. This can dramatically amplify hormonal fluctuations and significantly increase the risk of gynaecomastia and other serious adverse effects.

• Higher or prolonged HCG doses: The degree of hormonal disruption may increase with higher doses or longer duration of therapy, though the precise dose–response relationship in clinical practice is not fully characterised.

Adolescent males undergoing HCG treatment for prepubertal cryptorchidism or selected cases of delayed puberty (as specified in the relevant product SmPC) represent a particularly sensitive group, as puberty itself is already associated with transient gynaecomastia due to physiological hormonal fluctuations. Use in adolescents should be under specialist supervision, with careful monitoring throughout the course of treatment, in accordance with the licensed indication for the specific product being used.

Note: whilst variations in genes encoding aromatase or oestrogen receptors are sometimes discussed in the scientific literature, genetic predisposition to HCG-related gynaecomastia is not currently a routinely assessed factor in UK clinical practice and is not referenced in NICE or MHRA guidance; this should not be considered a standard clinical risk stratification tool.

Recognising the Signs and When to Seek Medical Advice

Gynaecomastia typically presents as a tender, firm disc of glandular tissue beneath one or both nipples; any breast change in men should be assessed by a clinician to exclude malignancy.

Gynaecomastia typically presents as a palpable, often tender, disc of glandular tissue beneath one or both nipples. It is important to distinguish true gynaecomastia — which involves actual glandular tissue — from pseudogynaecomastia, which is caused by excess fatty tissue without glandular proliferation and is not hormonally driven in the same way.

Common signs of gynaecomastia include:

• A firm or rubbery lump beneath the nipple area

• Breast tenderness or sensitivity, particularly in the early stages

• Swelling or enlargement of one or both breasts

• Nipple discharge (less common, but warrants prompt medical review)

Breast changes in men should always be assessed by a healthcare professional to exclude other causes, including breast cancer, which — whilst rare in men — does occur. In line with NICE guideline NG12 (Suspected cancer: recognition and referral), men aged 50 or over who present with a unilateral, firm subareolar mass, with or without nipple discharge or retraction, should be considered for urgent referral via the NHS two-week wait pathway. Suspicious skin changes, an unexplained axillary lump, or any rapidly growing, hard, or irregular mass should also prompt urgent assessment regardless of age.

If you are taking HCG and notice breast changes, contact your GP promptly. Do not discontinue prescribed medication without medical guidance, as abrupt cessation may have other hormonal consequences. Your GP can arrange appropriate investigations, which may include:

• Blood tests: morning total testosterone, sex hormone-binding globulin (SHBG), LH, FSH, oestradiol, prolactin, TSH, liver function tests, and renal function

• Clinical examination of the testes, with testicular ultrasound and tumour markers (beta-HCG, AFP) considered where clinically indicated

• Breast ultrasound or further imaging if required

Early assessment ensures that any underlying cause is identified and managed appropriately, and that serious pathology is not missed.

Managing and Treating HCG-Related Gynaecomastia

Management begins with dose reduction or discontinuation of HCG; persistent cases may require off-label SERMs or aromatase inhibitors under specialist supervision, or surgery if fibrosis has developed.

The management of HCG-related gynaecomastia depends on the severity of symptoms, the duration of the condition, and whether HCG therapy is ongoing or can be modified. A stepwise approach is generally recommended, beginning with identification and, where possible, treatment of the underlying cause.

Initial management strategies include:

• Dose reduction or discontinuation of HCG: Where clinically appropriate, reducing the HCG dose or stopping treatment may allow oestrogen levels to normalise and breast tissue changes to partially resolve, particularly if the condition is identified early before fibrosis develops. Any decision to modify or stop prescribed HCG should be made in consultation with the prescribing clinician.

• Monitoring: Mild, asymptomatic gynaecomastia that develops during necessary HCG therapy may be managed with watchful waiting and regular review, especially if the benefits of treatment outweigh the risks.

For more persistent or symptomatic cases, pharmacological options may be considered under specialist guidance:

• Selective oestrogen receptor modulators (SERMs) such as tamoxifen have been used to treat gynaecomastia by blocking oestrogen receptors in breast tissue. Evidence supports their use in early-stage gynaecomastia. However, this is an off-label use in the UK, and tamoxifen should only be initiated by a specialist after appropriate evaluation and with ongoing monitoring.

• Aromatase inhibitors (such as anastrozole or letrozole) reduce the conversion of testosterone to oestradiol and may help prevent or treat gynaecomastia in men on hormonal therapies. Their use in this context is also off-label in the UK and should similarly be initiated and supervised by a specialist.

Pharmacological treatment is generally most effective when gynaecomastia is of recent onset. Once the condition has been present for more than approximately 12 months, fibrosis of the glandular tissue is likely, and medical treatment becomes less effective. Surgical intervention — specifically subcutaneous mastectomy or liposuction-assisted techniques — may then be considered. Referral to a specialist breast or plastic surgery service would be appropriate in such cases; NHS funding criteria vary by Integrated Care Board (ICB) and should be discussed with the referring clinician.

For further guidance on management, clinicians and patients may wish to consult NICE CKS: Gynaecomastia and the relevant BNF monographs for tamoxifen and anastrozole.

Guidance From NHS and MHRA on HCG Use

HCG is a prescription-only medicine in the UK regulated by the MHRA; it must be used within licensed indications, and suspected adverse reactions including gynaecomastia should be reported via the Yellow Card scheme.

In the UK, HCG is a prescription-only medicine (POM) regulated by the Medicines and Healthcare products Regulatory Agency (MHRA). Licensed indications vary between products; for urinary HCG preparations, these typically include hypogonadotrophic hypogonadism in males, prepubertal cryptorchidism, and selected cases of delayed puberty. Clinicians should consult the SmPC for the specific product being prescribed, as indications and dosing recommendations differ between brands. HCG should only be used under the supervision of a qualified clinician, in accordance with the licensed indications and dosing guidance in the relevant SmPC.

NICE CKS guidance on hypogonadism in males and NICE guidance on fertility problems (including the current fertility guideline) outline when gonadotrophin therapy is appropriate within specialist care. These resources provide a framework for monitoring hormone levels and clinical response during treatment. Clinicians are encouraged to document informed consent discussions that include the risk of gynaecomastia and other hormonal side effects.

The MHRA has previously issued guidance highlighting the risks of unlicensed and counterfeit HCG products, particularly those sold online or through unregulated channels. The use of HCG for weight loss — sometimes promoted through unregulated diet programmes — is not supported by clinical evidence and is not a licensed indication in the UK. Patients should source all medicines through legitimate, registered pharmacies and exercise caution with online suppliers that do not require a valid UK prescription. The NHS and MHRA provide advice on how to buy medicines safely online.

Patients and healthcare professionals who have concerns about a suspected adverse drug reaction — including gynaecomastia — or who suspect they have purchased an unlicensed or counterfeit product, are encouraged to report this to the MHRA via the Yellow Card scheme at yellowcard.mhra.gov.uk. This scheme supports ongoing post-market surveillance of HCG products in the UK and helps to identify emerging safety signals.

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