Prolactin-producing pituitary tumours are the most common type of hormone-secreting growths found in the pituitary gland, a pea-sized organ at the base of the brain. While these tumours are not cancerous and not life-threatening, they can significantly affect fertility, hormone balance, and quality of life, making proper diagnosis and treatment essential.

Epidemiology

Prolactin-producing pituitary tumours, known as prolactinomas, represent a significant portion of pituitary health conditions. These growths account for up to 40 percent of all pituitary tumours that can make hormones, making them the most frequently diagnosed type of hormone-producing pituitary growth^[3]. The pituitary gland itself sits at the base of the brain and controls the production of many important hormones throughout the body.

The occurrence of prolactinomas varies considerably between men and women. The mean prevalence is estimated to be approximately 10 per 100,000 in men and 30 per 100,000 in women^[3]. This means women are roughly three times more likely to be diagnosed with this condition than men. The peak prevalence in women occurs between ages 25 and 34 years, which corresponds to the reproductive years when symptoms are more likely to be noticed^[3].

The size of the tumour also shows interesting patterns between the sexes. Prolactinomas are classified by size into two main categories: microprolactinomas, which are less than 1 centimetre in diameter, and macroprolactinomas, which are larger than 1 centimetre^[2]. Among people with prolactinomas, as many as 60 percent of males present with macroprolactinomas, while 90 percent of females present with microprolactinomas^[3]. This difference reflects the fact that women typically recognize symptoms sooner due to obvious changes like irregular menstrual periods or unexpected milk production from the breasts.

Prolactinomas can occur at any age, although they are rare in children and adolescents. When they do occur in young people, they typically cause delayed puberty^[2]. Most people with these tumours are under age 40 when diagnosed, with women often receiving their diagnosis at a younger age than men^[8].

Interestingly, about 5 to 10 percent of adults have what doctors call a “silent” prolactinoma that causes no symptoms at all. Many people don’t even know they have one, and doctors rarely treat these if they are discovered incidentally during brain imaging for other reasons^[4].

Causes

The exact cause of prolactinomas remains poorly understood by medical researchers. Scientists know that these tumours arise from monoclonal expansion of cells in the pituitary gland called lactotrophs, which are the cells responsible for producing prolactin^[3]. This means that a single cell undergoes changes that cause it to multiply abnormally, eventually forming a tumour.

Researchers have identified some genetic changes that appear to be involved in prolactinoma development. For example, overexpression of a gene called the pituitary tumour transforming gene (PTTG) and mutations of a receptor for fibroblast growth factor 4 (FGF4) have been found in pituitary growths, mainly prolactinomas^[3]. These genetic alterations represent somatic mutations, meaning they occur in individual cells during a person’s lifetime rather than being inherited from parents.

Most prolactinomas occur sporadically, which means they develop randomly without any identifiable inherited pattern. However, a small percentage can occur as part of familial syndromes, where multiple family members may be affected^[3]. One such condition is multiple endocrine neoplasia type 1 (MEN1), a genetic syndrome that affects multiple hormone-producing glands throughout the body. Between 15 and 60 percent of patients with MEN1 can develop a pituitary tumour, and the majority of these are prolactinomas^[3].

Other genetic conditions that can increase the risk of developing a prolactinoma include multiple endocrine neoplasia type 4 (MEN4) and familial isolated pituitary adenomas (FIPA)^[2]. In families with these conditions, multiple generations may experience pituitary tumours, though this represents a small minority of all prolactinoma cases.

Prolactinomas are almost always benign, meaning they are not cancerous. They are often sharply demarcated from surrounding tissue without evidence of invasion into nearby structures^[3]. However, a few prolactinomas can behave more aggressively, with invasion of surrounding local structures. These aggressive tumours generally have higher cell division activity and appear more abnormal under the microscope. True malignant prolactinomas, which spread to distant parts of the body, are extremely rare.

Risk Factors

While the exact causes of prolactinomas remain unclear, certain factors are associated with a higher likelihood of developing this condition. Understanding these risk factors can help with early recognition, though having risk factors does not mean a person will definitely develop a prolactinoma.

Gender is one of the most significant risk factors. Women are substantially more likely than men to be diagnosed with prolactinomas, particularly small ones^[2]. This gender difference may partly reflect that women notice symptoms earlier rather than a true difference in occurrence rates. Changes in menstrual cycles and unexpected breast milk production are obvious signs that prompt women to seek medical care, while symptoms in men, such as gradual loss of sexual interest or erectile problems, may be attributed to other causes or simply not reported.

Age represents another important factor. The peak age for diagnosis in women is between 25 and 34 years^[3]. Men tend to be diagnosed at an older age, often because their symptoms are less specific and may develop more gradually. People under age 40 are most commonly affected overall, although prolactinomas can occur at any age^[8].

Family history plays a role in a small percentage of cases. People with certain inherited genetic syndromes, particularly multiple endocrine neoplasia type 1 (MEN1), have a significantly elevated risk. If multiple family members have experienced pituitary tumours or other endocrine problems, genetic counselling and testing may be appropriate to assess individual risk.

It’s important to distinguish true prolactinomas from other conditions that can raise prolactin levels. Many medications can increase prolactin production without an actual tumour being present. Anti-nausea medications like metoclopramide and domperidone, acid-reducing medications like omeprazole, certain antidepressants including amitriptyline and fluoxetine (Prozac), and some medications used to treat mental health conditions like risperidone can all elevate prolactin^[4]. Other causes of raised prolactin include pregnancy, nipple stimulation and breastfeeding, stress, an underactive thyroid gland, and even some homeopathic and herbal medications.

Symptoms

The symptoms of a prolactinoma vary considerably depending on several factors, including how much prolactin the tumour produces, its size, and whether the affected person is male or female. Some people with very small prolactinomas may have no symptoms at all, while others experience significant health problems that affect their quality of life and fertility.

Too much prolactin in the blood, a condition called hyperprolactinemia, causes problems within the reproductive system, known as hypogonadism^[1]. Because of this, many symptoms are specific to either females or males, reflecting the different roles that reproductive hormones play in each sex.

In women, prolactinomas commonly cause menstrual irregularities. Women may experience periods that are not regular, infrequent, or absent altogether, a condition called amenorrhea^[1]. One of the most characteristic signs is galactorrhea, which is milky discharge from the breasts when a person is not pregnant or breastfeeding^[2]. The breasts may also feel sore or tender. Many women experience vaginal dryness, which can make penetrative sex uncomfortable or painful. Difficulty getting pregnant, known as infertility, is common because high prolactin levels interfere with ovulation^[1]. Some women may also develop acne and extra body and facial hair.

In men, the symptoms are often less obvious, which contributes to delayed diagnosis. Men with prolactinomas frequently experience erectile dysfunction, which is difficulty achieving or maintaining an erection^[1]. Loss of interest in sex, called low libido, is common. Male infertility can occur because high prolactin levels interfere with sperm production. Over time, men may notice less body and facial hair, smaller muscles, and even enlargement of breast tissue, called gynecomastia^[1].

Symptoms that can affect anyone regardless of sex include difficulty getting pregnant, reduced sex drive, and weight gain^[2]. If left untreated over a long period, high prolactin levels can lead to bone loss, progressing from osteopenia (mild bone loss) to osteoporosis (severe bone loss with increased fracture risk)^[2].

When a prolactinoma grows large enough, it can press on surrounding structures and cause additional symptoms unrelated to hormone production. Headaches are common with larger tumours^[2]. If the tumour presses on the optic nerves, which pass near the pituitary gland, vision problems can develop. These may include double vision, decreased peripheral vision (the ability to see to the sides), or other vision changes^[1]. Some people experience sinus pain or pressure, nausea and vomiting, or problems with their sense of smell, called dysosmia^[2].

Rarely, prolactinomas can cause more severe symptoms related to compression of the pituitary gland itself. This can lead to reduced production of other pituitary hormones, causing symptoms like extreme fatigue, weight loss, or sensitivity to cold temperatures.

It’s worth noting that women often notice symptoms earlier than men because changes in menstrual periods or unexpected breast milk production are obvious and concerning signs. Males and females who have reached menopause often have delayed diagnosis because their symptoms may be less specific or attributed to other causes^[2].

Prevention

Currently, there are no proven methods to prevent the development of prolactinomas. Because the exact causes of these tumours remain poorly understood, and most cases occur sporadically without identifiable triggers, specific prevention strategies have not been established.

However, there are approaches that can help with early detection and prevent complications if a prolactinoma does develop. Being aware of the symptoms and seeking medical attention promptly when they appear is crucial. Women who notice irregular menstrual periods, unexpected breast milk production, or difficulty becoming pregnant should consult a healthcare provider. Men experiencing erectile dysfunction, reduced sex drive, or unexplained infertility should also seek medical evaluation, as these symptoms can sometimes be dismissed or attributed to stress or aging.

For people with a family history of pituitary tumours or genetic syndromes associated with increased prolactinoma risk, such as multiple endocrine neoplasia type 1 (MEN1), genetic counselling may be valuable. While genetic testing cannot prevent prolactinomas, it can help identify individuals at higher risk who may benefit from closer monitoring.

Regular medical check-ups are important for general health and can sometimes lead to earlier detection of health problems, including hormone imbalances. Being open with healthcare providers about all symptoms, even those that may seem embarrassing or unrelated, helps ensure proper evaluation.

One practical prevention measure relates to medication use. Because certain medications can raise prolactin levels and potentially be confused with prolactinomas, it’s important to use these medications only when necessary and under proper medical supervision. Anti-nausea drugs, some acid-reducing medications, certain antidepressants, and medications used to treat mental health conditions should be taken as prescribed, and any concerning symptoms should be reported to a doctor^[4].

Maintaining overall health through a balanced diet, regular physical activity, adequate sleep, and stress management supports the body’s natural hormone balance and overall wellbeing, though these measures have not been proven to specifically prevent prolactinomas. Good bone health is particularly important because untreated high prolactin levels can lead to osteoporosis. Ensuring adequate calcium and vitamin D intake through diet or supplements, along with weight-bearing exercise, helps protect bone strength.

Pathophysiology

Understanding how prolactinomas develop and cause symptoms requires knowledge of the normal function of the pituitary gland and the hormone prolactin. The pituitary gland, despite being only pea-sized, serves as the “master gland” of the body, controlling the production of numerous hormones that regulate growth, metabolism, reproduction, and stress responses.

Prolactin is a hormone naturally produced by specialized cells in the pituitary gland called lactotrophs. These cells are located primarily in the lateral parts of the anterior (front) portion of the pituitary gland^[3]. Prolactin’s most well-known role is stimulating milk production after childbirth, which is why it’s sometimes called the “milk hormone”^[4]. However, prolactin also plays roles in energy production, fertility, sexual desire, and maintaining the body’s internal balance.

In women, prolactin works together with the hormone estrogen to produce breast milk. Following childbirth, when prolactin levels are naturally high, menstrual periods stop while breastfeeding continues, and sexual interest typically decreases^[7]. Once breastfeeding stops, prolactin levels drop back to normal, and the normal menstrual cycle resumes. Both men and women produce prolactin, though men produce it in smaller amounts, and its function in men is less clearly understood.

In the normal pituitary gland, prolactin production is controlled by dopamine, a brain chemical that acts as a brake on prolactin release. When dopamine levels are adequate, prolactin production stays within normal ranges. However, when a prolactinoma develops, this normal control mechanism fails. The tumour cells produce prolactin continuously without responding properly to dopamine’s inhibitory signals.

A prolactinoma develops through monoclonal expansion, meaning it grows from a single lactotroph cell that has undergone genetic changes^[3]. This altered cell begins dividing repeatedly, creating more identical cells that all produce excessive amounts of prolactin. Most prolactinomas are benign and well-demarcated from surrounding tissue, growing slowly over months or years. Some may not grow at all once they reach a certain size^[4].

The elevated prolactin levels caused by the tumour have widespread effects throughout the body. In both men and women, high prolactin suppresses the production and release of hormones that control reproduction, specifically follicle-stimulating hormone (FSH) and luteinizing hormone (LH)^[4]. In women, these hormones normally cause release of the sex hormone estrogen and stimulate the ovaries to produce eggs, processes essential for a normal menstrual cycle. In men, FSH and LH cause the release of testosterone and stimulate sperm production from the testicles.

When prolactin levels are chronically elevated, the reduced levels of estrogen in women and testosterone in men lead to many of the symptoms associated with prolactinomas. The lack of estrogen causes menstrual irregularities, vaginal dryness, and eventually bone loss. The lack of testosterone in men causes erectile dysfunction, reduced muscle mass, loss of body hair, and decreased bone density. Infertility in both sexes results from disrupted hormone signalling that prevents normal egg and sperm production.

The unexpected production of breast milk in non-pregnant, non-breastfeeding women occurs because prolactin directly stimulates the milk-producing glands in breast tissue, especially when estrogen is also present. Breast tissue development in men with prolactinomas results from the hormonal imbalance created by low testosterone combined with other factors.

Large prolactinomas can cause additional problems through physical pressure. As the tumour grows, it may press on the remaining normal pituitary tissue, potentially interfering with the production of other pituitary hormones. This can cause a condition called hypopituitarism, where the pituitary gland doesn’t produce adequate amounts of one or more hormones. If the tumour grows upward, it may compress the optic nerves that pass just above the pituitary gland, causing vision problems. Pressure on surrounding structures can also cause headaches and other neurological symptoms.