Can testosterone treatment cause high prolactin levels? This question concerns many men prescribed testosterone replacement therapy (TRT), particularly those experiencing unexpected symptoms during treatment. Current evidence indicates that testosterone therapy does not directly cause hyperprolactinaemia as a pharmacological effect. However, prolactin levels may occasionally rise during TRT due to indirect mechanisms, medication interactions, or unmasking of pre-existing pituitary conditions. Understanding the complex relationship between testosterone and prolactin is essential for safe, effective hormone management. This article examines the evidence, explores potential mechanisms, and provides guidance on monitoring and managing prolactin levels during testosterone treatment in accordance with UK clinical practice.

Understanding Prolactin and Testosterone: The Hormonal Connection

Prolactin is a hormone primarily produced by the anterior pituitary gland, best known for its role in lactation. However, prolactin serves multiple functions in both women and men, including regulation of reproductive function, metabolism, and immune system modulation. In men, prolactin levels are normally low, with reference ranges varying between laboratories—typically between 86–324 mIU/L. It is always important to refer to your local laboratory's specific reference ranges.

Testosterone, the principal male sex hormone, is produced mainly by the Leydig cells in the testes under the control of luteinising hormone (LH) from the pituitary gland. Testosterone is essential for maintaining libido, erectile function, muscle mass, bone density, mood regulation, and spermatogenesis. The relationship between prolactin and testosterone is complex. Elevated prolactin levels (hyperprolactinaemia) can suppress the hypothalamic-pituitary-gonadal (HPG) axis, leading to reduced gonadotrophin-releasing hormone (GnRH) secretion, which in turn decreases LH and follicle-stimulating hormone (FSH) production. This cascade results in reduced endogenous testosterone production and may cause hypogonadal symptoms.

Whilst prolactin can affect testosterone levels, the evidence for testosterone directly influencing prolactin secretion is less established. The interplay between these hormones is regulated through multiple feedback mechanisms, and disruption at any level can lead to clinical manifestations. Understanding this hormonal connection is crucial when considering testosterone replacement therapy (TRT). Men prescribed testosterone treatment require monitoring of key parameters including haematocrit, PSA (prostate-specific antigen), and testosterone levels to ensure therapeutic efficacy whilst minimising potential adverse effects. It's also important to note that exogenous testosterone suppresses spermatogenesis and is generally unsuitable for men trying to conceive.

Can Testosterone Treatment Cause High Prolactin Levels?

The relationship between testosterone treatment and prolactin levels is not straightforward, and there is no direct, established causal link between exogenous testosterone administration and elevated prolactin. Current evidence suggests that testosterone replacement therapy (TRT) does not typically cause hyperprolactinaemia as a direct pharmacological effect. Most clinical studies examining men on TRT have not demonstrated consistent increases in prolactin levels attributable to the testosterone itself.

This is supported by UK regulatory information—the MHRA-approved Summaries of Product Characteristics (SmPCs) for testosterone preparations such as Testogel and Nebido do not list hyperprolactinaemia as a recognised adverse effect. Similarly, NICE Clinical Knowledge Summaries on testosterone deficiency do not identify elevated prolactin as an expected consequence of treatment.

However, the clinical picture is more nuanced. Some men may experience changes in prolactin levels during testosterone therapy due to indirect mechanisms rather than a direct effect of the medication. It is important to distinguish between testosterone causing elevated prolactin and testosterone therapy coinciding with or unmasking pre-existing conditions that affect prolactin secretion.

In clinical practice, if prolactin levels rise during TRT, clinicians should investigate alternative explanations rather than automatically attributing the elevation to the testosterone treatment. If severe headache, visual symptoms, or marked hyperprolactinaemia occur during treatment, urgent specialist endocrine or neurosurgical advice should be sought, and temporary discontinuation of TRT may be appropriate pending assessment.

Why Prolactin Levels May Rise During Testosterone Therapy

Whilst testosterone itself does not directly elevate prolactin, several mechanisms may explain why some men experience raised prolactin levels during testosterone treatment. Understanding these potential pathways is essential for appropriate clinical management.

Aromatisation to oestradiol represents one theoretical mechanism. Testosterone undergoes peripheral conversion to oestradiol via the enzyme aromatase, particularly in adipose tissue. In some men, especially those with higher body mass index or those receiving higher testosterone doses, oestradiol levels may rise. Oestradiol can potentially stimulate prolactin secretion from lactotroph cells in the pituitary gland, though the clinical significance of this pathway in men on TRT requires further research.

Unmasking of pre-existing pituitary pathology is another important consideration. Some men commence testosterone therapy without comprehensive baseline endocrine assessment. A prolactin-secreting pituitary adenoma (prolactinoma) may have been present but undetected prior to TRT initiation. The symptoms of hypogonadism and hyperprolactinaemia overlap considerably (reduced libido, erectile dysfunction, fatigue), and the prolactinoma may have been the primary cause of the low testosterone rather than primary hypogonadism.

Medication interactions should also be considered. Many men on testosterone therapy take concurrent medications that can elevate prolactin levels, including antipsychotics (particularly risperidone and amisulpride), some antidepressants, antiemetics (metoclopramide, domperidone), opioids, and certain antihypertensives (verapamil, methyldopa). Additionally, stress, sleep deprivation, and intense physical exercise can transiently elevate prolactin levels.

Macroprolactin, a biologically inactive complex of prolactin bound to immunoglobulin, can cause falsely elevated prolactin readings without clinical significance and should be considered when interpreting results that don't match the clinical picture.

Symptoms and Risks of Elevated Prolactin in Men

Hyperprolactinaemia in men produces a constellation of symptoms that can impact quality of life and overall health. Sexual dysfunction is often the most prominent manifestation. Elevated prolactin suppresses GnRH pulsatility, leading to reduced LH and FSH secretion, which decreases testosterone production. This results in reduced libido, erectile dysfunction, and decreased spontaneous erections. Some men may also experience difficulty achieving orgasm or reduced ejaculatory volume. These symptoms may be particularly concerning for men who initiated testosterone therapy specifically to address sexual dysfunction.

Gynaecomastia (breast tissue enlargement) and galactorrhoea (inappropriate breast milk production) can occur, though galactorrhoea is relatively uncommon in men compared to women. These physical changes can cause significant psychological distress and body image concerns. Men may also experience metabolic consequences, including increased visceral adiposity, reduced muscle mass, and decreased bone mineral density over time, potentially increasing fracture risk.

Psychological symptoms may occur in some men with hyperprolactinaemia, including low mood, anxiety, irritability, and reduced motivation, though evidence for direct causation is mixed. These effects may partly reflect the impact of concurrent hypogonadism rather than direct prolactin effects.

The risks associated with persistent hyperprolactinaemia extend beyond symptomatic burden. Chronic elevation may indicate underlying pituitary pathology, particularly a prolactinoma. Macroadenomas (>10mm) can cause mass effects including headaches, visual field defects (classically bitemporal hemianopia from optic chiasm compression), and hypopituitarism affecting other pituitary hormones.

Red flag symptoms requiring urgent medical attention include severe or sudden-onset headache, visual disturbances (particularly peripheral vision loss), or cranial nerve palsies. Suspected pituitary apoplexy (sudden haemorrhage or infarction of a pituitary tumour) is a medical emergency requiring immediate assessment. Early detection and appropriate management are essential to prevent long-term complications.

Monitoring and Managing Prolactin Levels on Testosterone Treatment

Baseline assessment before initiating testosterone therapy should include measurement of morning total testosterone (on two occasions), LH, FSH, sex hormone-binding globulin (SHBG), full blood count (including haematocrit), and PSA (in men over 40 or at increased risk of prostate cancer). Prolactin should be checked if secondary hypogonadism is suspected or if symptoms suggest possible hyperprolactinaemia. Oestradiol testing is not routinely required but may be considered if gynaecomastia is present. NICE guidance recommends excluding secondary causes of hypogonadism, including hyperprolactinaemia, before diagnosing primary testosterone deficiency.

Routine monitoring during testosterone therapy should follow a structured protocol. Standard monitoring includes testosterone levels, haematocrit (target <54%; adjust or withhold treatment if higher), and PSA according to age and risk. Prolactin levels should be checked if symptoms suggestive of hyperprolactinaemia develop (sexual dysfunction not improving despite adequate testosterone levels, gynaecomastia, galactorrhoea, headaches, or visual disturbances). When measuring prolactin, samples should ideally be taken mid-morning after a period of rest, as prolactin exhibits diurnal variation and is stress-sensitive. A single elevated result should be confirmed with repeat testing before pursuing further investigation.

When hyperprolactinaemia is confirmed (levels above the local laboratory reference range on two occasions), systematic investigation is warranted. This includes:

• Medication review: Identify and, if possible, discontinue or substitute prolactin-elevating drugs

• Macroprolactin assessment: Request macroprolactin testing, as this biologically inactive complex can cause falsely elevated results without clinical significance

• Pituitary MRI: Indicated for persistent elevation after excluding other causes, typically if levels exceed 1000 mIU/L, or when symptoms suggest pituitary pathology

• Additional pituitary function testing: Assess other pituitary hormones if structural lesion suspected

Management strategies depend on the underlying cause. If a prolactinoma is identified, dopamine agonist therapy (cabergoline or bromocriptine) is first-line treatment and highly effective. Testosterone therapy can often be continued alongside dopamine agonist treatment, with both medications addressing different aspects of the hormonal dysfunction. If excessive aromatisation is suspected (elevated oestradiol with modestly raised prolactin), dose adjustment of testosterone may be considered. Aromatase inhibitors should only be used under specialist endocrinology supervision, as they are off-label in men and have limited long-term safety data.

Patient education is paramount. Men should be advised to report new or worsening sexual dysfunction, breast changes, persistent headaches, or visual disturbances promptly. They should understand that whilst testosterone treatment itself does not typically cause high prolactin, monitoring remains important to detect any hormonal imbalances. Patients should be reassured that most cases of mild prolactin elevation are manageable and do not necessitate discontinuation of testosterone therapy. Shared decision-making and regular review ensure optimal outcomes and patient safety throughout testosterone treatment.

Any suspected adverse reactions to testosterone therapy should be reported to the MHRA via the Yellow Card scheme.

Frequently Asked Questions