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Impact of hyperprolactinemia on sexual function
Hyperprolactinemia, defined by elevated levels of prolactin, has a significant negative impact on sexual function through effects such as reduced sexual desire
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Introduction
Hyperprolactinemia, defined by elevated levels of prolactin,has a significant negative impact on sexual function through effects such as reduced sexual desire in men and women and erectile dysfunction in men. Prolactin is a hormone secreted by lactotroph cells in the anterior pituitary gland.1 In this Expert Opinion, we provide an overview of hyperprolactinemia and its influence on sexual function.
Neuroendocrine pathways involved in prolactin-mediated sexual function
Prolactin-mediated sexual function involves complex neuroendocrine pathways between the brain, pituitary gland, and gonads that influence various aspects of sexual behavior. Dopamine produced by the hypothalamus inhibits prolactin secretion. Dopamine is transported to the pituitary gland via the pituitary stalk, binds to specific dopamine receptors on pituitary lactotroph cells, and hereby reduces prolactin synthesis and secretion, maintaining levels of prolactin within normal ranges. Prolactin stimulates dopamine release, acting in a self-regulatory manner.1
Prolactin appears to play a role in the central regulation of sexual behavior and activity, primarily by influencing the effects of the dopaminergic and serotoninergic systems on sexual function. Prolactin receptors are expressed in various areas of the brain that are involved in the sexual response cycle, suggesting a direct effect of prolactin on sexual desire regulation. Experiments in animal models have indicated that elevated prolactin levels generally have an inhibitory effect on sexual behavior and activity. Notably, prolactin levels in the bloodstream rise after orgasm in both sexes, suggestinga potential role in the immediate regulation of postorgasmic sexual arousal.1
High prolactin levels suppress the pulsatile release of hypothalamic gonadotropin-releasing hormone, leading to decreased production of the pituitary gonadotropins luteinizing hormone and follicle-stimulating hormone. Furthermore, high prolactin levels can also directly inhibit the release of luteinizing and follicle-stimulating hormones from the pituitary gland, leading to hypogonadotropic hypogonadism. This disturbance of gonadotropin release also disrupts stimulation of testosterone production in the testis and stimulation of ovarian support of the different phases of the menstrual cycle and ovulation.
The impact of hyperprolactinemia on sexual function in men
The precise physiological role of prolactin in men is still not fully understood. Male reproductive function remains unaffected in prolactin receptor knockout mice, despite the receptors expression in various male anatomical structures such as the brain, testis, and penis.
Hyperprolactinemia has a negative effect on sexual desire in men. This could be attributable in part to reduced testosterone levels, but in addition appears to directly impact the role of prolactin in sexual desire. This reduction in sexual desirei nduced by high prolactin levels may be influenced by the central action of prolactin on its receptor. Prolactin levels above 32 ng/mL are associated with hypoactive sexual desire in men.2 Erectile dysfunction is common in men with hyperprolactinemia, but is probably secondary to low testosterone levels. Although animal studies suggest a role of prolactin in erectile function by directly inhibiting smooth muscle relaxation in the penile corpus cavernosum, a direct relationship between hyperprolactinemia and erectile dysfunction is still debated.2,
Notably, not all men with hyperprolactinemia experience sexual symptoms, and the degree of sexual dysfunction varies among individuals. Furthermore, other factors, such as the underlying cause of hyperprolactinemia or disturbed production of other pituitary hormones, can also influence sexual function in men with high prolactin levels.
On the other hand, hyperprolactinemia is rarely found in men with erectile dysfunction, with a recent meta-analysis showing a prevalence of 1%-2% in men who seek consulting for sexual dysfunction.2 Guidelines do not recommend screening men with erectile dysfunction for hyperprolactinemia,unless they have low gonadotropin and testosterone levels.
The impact of hyperprolactinemia on sexual function in women
Hyperprolactinemia in women affects sexual function and fertility. Likewise in women, hyperprolactinemia can lead to hypoactive sexual desire through two parallel mechanisms.This may be a direct result of the inhibitory action of prolactin on the hypothalamic–pituitary-gonadal axis, and elevated prolactin levels can also interfere with physiological processes involved in sexual arousal and vaginal lubrication. Some women with hyperprolactinemia may experience difficulties in achieving orgasm or find that their overall sexual satisfaction is impacted, while others do not report sexual dysfunction. In women, oligomenorrhea can occur with serum prolactin >50 ng/mL, while prolactin levels >100 ng/mL can cause vaginal dryness and other symptoms of hypogonadism.1
The report of the international consultation on sexual medicine suggests measuring prolactin in premenopausal women presenting with sexual dysfunction and amenorrhea or galactorrhea, as hyperprolactinemia is a treatable cause of female sexual dysfunction.4
Prevalence, symptoms, and causes of hyperprolactinemia
Mean prevalence of hyperprolactinemia is approximately 10 per 100.000 in men and 30 per 100.000 in women. The most common symptoms of hyperprolactinemia in men are erectile dysfunction and reduced sexual desire, whereas women mainly present with galactorrhea, menstrual cycle irregularity,and low sexual desire. Symptoms associated with high prolactin levels vary between individuals and depending on the cause of the hyperprolactinemia.
Various factors may underly hyperprolactinemia. A prolactin-secreting pituitary tumor (prolactinoma) is the most common functional pituitary tumor. Men often present with larger tumors (macroprolactinomas), which can cause tumor mass effects such as headache and visual disturbances, whereas premenopausal women commonly have smaller tumors (microprolactinomas). Large nonfunctional pituitary tumors or skull base tumors can disrupt the connection between the hypothalamus and pituitary gland by damaging the pituitary stalk. This so-called “stalk effect” disrupts dopaminergic inhibition of prolactin secretion, leading to hyperprolactinemia.
Furthermore, certain medications, such as antipsychotics (eg, risperidone, haloperidol) and prokinetics (eg, domperidone, metoclopramide) can induce hyperprolactinemia. These drugs act as dopamine antagonists, blocking dopamine receptors and thereby reducing the inhibitory effect of dopamine on lactotroph cells. It is important to emphasize that drug-induced hyperprolactinemia is much more common than generally thought. Many other medical conditions,such as chronic kidney disease and hypothyroidism, can also lead to increased prolactin levels. A mild increase in serum prolactin levels can be related to the presence of biologically inactive macroprolactinemia or induced by stress, such as venipuncture. This serum prolactin level increase is a physiological response and not a warning sign for hyperprolactinemia.3
Diagnostic evaluation and treatment of patients with hyperprolactinemia
Identifying the underlying cause of hyperprolactinemia is crucial for appropriate management and treatment. Diagnosis involves serial prolactin sampling to confirm hyperprolactinemia and subsequent scanning of the pituitary gland with magnetic resonance imaging when hyper prolactinemiais confirmed. Mildly elevated prolactin levels also warrant endocrinological evaluation because this finding may be asign of an underlying disease or a nonfunctional pituitary adenoma.
Treatment options for hyperprolactinemia-related sexual dysfunction typically focus on reducing prolactin levels and addressing the underlying cause. Dopamine agonists are the primary treatment for hyperprolactinemia. Neuro surgical treatment can be considered for selected cases. Drug-induced hyperprolactinemia can be managed by discontinuing or dose escalating the accountable medication. Normalizing prolactin levels restores proper functioning of the hypothalamic–pituitary gonadal axis. Treatment of hyperprolactinemia improves sexual desire in men and women, while the impact on erectile function is limited.2
Because sexual dysfunction is common in both male and female patients presenting with hyperprolactinemia, acknowledgement of this topic is important during consultations and assessments of sexual function in both men and women. Addressing the psychological and emotional aspects of sexual dysfunction may also be helpful, particularly for cases in which hyperprolactinemia-related sexual dysfunction leads to patient distress. Regular monitoring of prolactin levels and sexual function during treatment is key to ensuring that treatment is effective.
Conclusion
Hyperprolactinemia may lead to reduced sexual desire and impaired sexual function both in men and women. Improvement of sexual desire is the main benefit of treatment that normalizes prolactin levels.
