Prolactin: Should Men with Erectile Dysfunction Be Tested ?

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Nelson Vergel

Prolactin is a hormone produced in the pituitary gland that is known for supporting lactation in women but also have many other functions on immune response, myelin coating on nerves, and also enhances LH receptors on testicular Leydig cells so that testosterone can be produced.

Prolactin levels peak during REM sleep, and in the early morning. Levels can rise after exercise, meals, sexual intercourse, minor surgical procedures, or following epileptic seizures.

High prolactin can decrease testosterone and cause sexual dysfunction.


Normal prolactin blood level in men range between 2 and 18 ng/mL

High blood levels of prolactin are more common than low levels. Hyperprolactinemia (Prolactin > 150 ng/dL) is the most frequent abnormality of the anterior pituitary tumors, termed prolactinomas. Prolactinomas may disrupt the hypothalamic-pituitary-gonadal axis as prolactin tends to suppress the secretion of gonadotropin-releasing hormone (GnRH- a hormone responsible for activating the pituitary to male Luteinizing and Follicle Stimulating hormones- LH and FSH) therefore causing low testosterone and sperm production. Such hormonal changes may manifest as impotence in males. Inappropriate lactation in men is another important clinical sign of prolactinomas (yes, men's breast tissue can produce small amounts of milk if high prolactin blood levels are present).

However, low prolactin blood levels have also been found to be linked to sexual dysfunction and other issues.
Low Prolactin Is Associated with Sexual Dysfunction & Psychological/Metabolic Issues

Since prolactin seems to be involved in immune response, keeping healthy levels is important.

Substantial elevation in prolactin (>150 ng/mL) usually indicates a pituitary tumor. Very high levels of prolactin are associated with larger tumors. Prolactinomas are classified as microadenomas (<10 mm) and macroadenomas (>10 mm). The finding of a substantial elevation in blood levels of prolactin association with a pituitary lesion larger than 10 mm by radiographic analysis supports the diagnosis of a macroprolactinoma.

Modest levels of prolactin elevation (25- 100 ng/mL) may be associated with several diagnoses. All other causes of hyperprolactinemia should be excluded before a tumor is considered. Primary hypothyroidism and chronic renal disease are associated with elevations in prolactin, probably because of altered metabolism or clearance of prolactin.

Some medications can increase prolactin blood levels in men, as shown in this table (source: Pharmacological causes of hyperprolactinemia)

Who Should Be Tested for High Prolactin:

1- Men not on testosterone replacement therapy (TRT) with very low levels of total testosterone (T level <150 ng/dL), especially if lower than normal LH is observed. For such male patients, testing for prolactin is used as screening for a potential pituitary gland problem (these men are referred to MRI)

2- Men with fluid production from their nipples. This has been observed in some men on anabolic steroids.

3- Men who have been on optimized TRT (TT levels above 500 ng/dL with free testosterone > 2 percent of TT) who complain of erectile dysfunction after at least 8-12 weeks of therapy. Prolactin is not usually included in baseline lab work due to the cost and the fact that the incidence of high prolactin in men is about 5 percent, making it not economically justified. However, if baseline total testosterone is very low or optimized TRT fails to improve ED, prolactin testing could be justified.


Treatment of High Prolactin:

Due to its long half-life and strong attachment to the prolactin receptor, the use of cabergoline at 0.25- 1 mg per week has become the main treatment of choice as a way to decrease prolactin in men on TRT.

Cabergoline (brand names Dostinex and Cabaser), an ergot derivative, is a potent dopamine receptor agonist on D2 receptors. In vitro, rat studies show cabergoline has a direct inhibitory effect on pituitary lactotroph (prolactin) cells. It is frequently used as a first-line agent in the management of prolactinomas due to higher affinity for D2 receptor sites, less severe side effects, and more convenient dosing schedule than the older treatment for this condition (bromocriptine).

In a small study done in men with very high prolactin (>1000 ng/dL) due to a pituitary tumor, an escalating dosing regimen of cabergoline improved prolactin and sexual function.

In another pilot study that enrolled men with ED who had with a median prolactin blood level of 31 ng/mL, a dose of 0.5 mg twice daily of cabergoline brought levels down to a median of 4.9 ng/mL and improved sexual function.

It is advisable to start at 0.2-0.5 mg once per week and then recheck blood levels after 4 weeks to ensure that prolactin is not reduced under 2 ng/dL (both high and low prolactin can cause ED).

Note: Some online forums have fueled the unmonitored use of cabergoline as a way to boost erectile function and decrease refractory (the time that takes to recover before having sex again) time after orgasm. My concern with unmonitored use of this drug is that men may be driving their prolactin too low which results in the opposite effect they are seeking.

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Defy Medical TRT clinic doctor
Interesting to see the drugs listed in the table of hyperprolactinemia inducing agents. We frequently see men who are on opiate medication for pain management who have hypogonadism. It seems prudent to also add prolactin to the test panel when assessing patients on these medications.

The table also mentions alprazolam, a benzodiazepine. Patients using benzodiazepines chronically also always seem to have deficient T levels.

Great post. With all the people on anti-depressants and various other drugs listed it is good to know when testing for prolactin might be appropriate.

Nelson Vergel

Higher prolactin blood levels protect against diabetes and impaired glucose regulation: a population-based study.


Wang T, et al.

Diabetes Care. 2013 Jul;36(7):1974-80. doi: 10.2337/dc12-1893. Epub 2013 Jan 22.


OBJECTIVE: Prolactin is a major stimulus for the &#946;-cell adaptation during gestation and guards postpartum women against gestational diabetes. Most studies of the role of prolactin on glucose metabolism have been conducted in humans and animals during pregnancy. However, little is known concerning the association between circulating prolactin and glucose metabolism outside pregnancy in epidemiological studies. We aimed to determine whether the variation of circulating prolactin concentration associates with diabetes and impaired glucose regulation (IGR) in a cross-sectional study.

RESEARCH DESIGN AND METHODS: We recruited 2,377 participants (1,034 men and 1,343 postmenopausal women) without hyperprolactinemia, aged 40 years and older, in Shanghai, China. Diabetes and IGR were determined by an oral glucose tolerance test. Multinomial logit analyses were performed to evaluate the relationship of prolactin with diabetes and IGR.

RESULTS: Prolactin levels decreased from normal glucose regulation to IGR to diabetes. Multinomial logit analyses, adjusted for potential confounding factors, showed that high circulating prolactin was associated with lower prevalence of diabetes and IGR. The adjusted odds ratios (95% CI) for IGR and diabetes for the highest compared with the lowest quartile of prolactin were 0.54 (95% CI 0.33-0.89) and 0.38 (0.24-0.59) in men and 0.54 (0.36-0.81) and 0.47 (0.32-0.70) in women.

CONCLUSIONS: High circulating prolactin associates with lower prevalence of diabetes and IGR in the current study. Further studies are warranted to confirm this association.
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Nelson Vergel

Auriemma RS, Galdiero M, Vitale P, et al. Effect of Chronic Cabergoline Treatment and Testosterone Replacement on Metabolism in Male Patients with Prolactinomas. Neuroendocrinology.

Introduction: Hyperprolactinemia and hypogonadism are reportedly associated with impaired metabolic profile. The current study aimed at investigating the effects of testosterone replacement and cabergoline (CAB) treatment on metabolic profile in male hyperprolactinemic patients.

Patients and Methods: Thirty-two men with prolactinomas, including 22 with total testosterone (TT) <8 nmol/l (HG, 69%) and 10 with TT >8 nmol/l (non-HG, 31%) entered the study. In all patients, metabolic parameters were assessed at diagnosis and after 12 and 24-month treatment.

Results: Compared to non-HG, at baseline HG patients had higher waist circumference (WC). TT significantly correlated with BMI.

Twelve-month CAB induced PRL normalization in 84%. HG prevalence significantly decreased (28%) and non-HG prevalence significantly increased (72%). Anthropometric and lipid parameters, fasting insulin (FI), ISI0, HOMA-beta and HOMA-IR significantly improved compared to baseline.

TT was the best predictor for FI. TT percent change (Delta) significantly correlated with DeltaCholesterol, DeltaWeight and DeltaBMI.

Compared to non-HG, HG patients had higher weight, BMI, WC and HOMA-beta.

In HG, testosterone replacement was started. After 24 months, PRL normalised in 97%. HG prevalence significantly decreased (6%) and non-HG prevalence significantly increased (94%). Anthropometric and lipid parameters, FI, ISI0, HOMA-beta and HOMA-IR significantly improved compared to baseline, with FI, ISI0, HOMA-beta and HOMA-IR further ameliorating compared to 1-year. Compared to non-HG, HG patients still had higher weight, BMI and WC.

Conclusions: In hyperprolactinemic hypogonal men, proper testosterone replacement induces a significant improvement in metabolic profile, even though the amelioration in lipid profile might reflect the direct action of CAB.

Nelson Vergel

Patients with prolactinomas come to clinical recognition because of the effects of elevated prolactin (PRL) levels or tumor mass effects. The most typical symptoms of hyperprolactinemia in women are amenorrhea (94%) and galactorrhea (85%). Non-puerperal galctorrhea may occur in 5-10% of normally menstruating, normoprolactinemic women, and therefore is suggestive, but not definitive of hyperprolactinemia.

Hyperprolactinemia inhibits the pulsatile secretion of gonadotropin releasing hormone, alters the pattern of release of luteinizing hormone and follicle-stimulating hormone, and suppresses gonadal steroidogenesis, thereby resulting in hypogonadotropic hypogonadism in both sexes. This results in anovulation and amenorrhea in women, erectile dysfunction in men, and decreased libido, infertility and osteopenia in both sexes. Treatment that normalizes PRL levels generally restores normal libido and sexual/reproductive function.

Management of a Prolactinoma

Nelson Vergel

Stress Can Increase Prolactin. Prolactin Protects Immune Function During Stress.


Non-puerperal lactation and/or hyperprolactinemia in humans have been related to psychological variables in a variety of ways: (1) Non-puerperal nursing; (2) Pseudopregnancy; (3) Rapid weight gain; (4) Psychogenic galactorrhea; (5) Acute prolactin responses to psychological stress; (6) High prolactin levels in persons who cope passively in real life stress situations; (7) Paternal deprivation in women with pathological hyperprolactinemia; (8) Clinical onset of prolactinomas following life-events. Publications on the above subjects are scattered in the literature as curiosities, anecdotal case-reports or unexplained associations, as there is no theoretical frame of reference to accommodate them. We propose that prolactin is a component of a biological, "maternal", subroutine, adaptive to the care of the young, which promotes accumulation of fat for the extraordinary expenses of pregnancy and lactation, the production of milk and maternal behavior. In an attempt to characterize the stimuli responsible for the activation of the maternal subroutine in the absence of pregnancy we studied the hormonal profiles of female volunteers during three types of sessions under hypnosis: (1) Relaxation-only, control sessions; (2) Sessions in which a fantasy of "nursing" was induced; (3) Sessions of evocations of memories. Prolactin surges were related to the evocation, with rage, of humiliating experiences, but not with the fantasy of nursing. Cortisol surges were related to surprise and shock and were negatively associated with prolactin. In conclusion--Prolactin and cortisol are measurable markers of two different, and alternative, coping strategies to "psychological stress".

Book Source:
Prolactin, psychological stress and environment in humans: adaptation and maladaptation

by Sobrinho, Luis Gonçalves

Nelson Vergel

When getting a prolactin blood test, do so in a fasted stated since glucose/insulin may decrease prolactin.

Circadian Insulin, GH, Prolactin, Corticosterone and Glucose Rhythms in Fed and Fasted Rats L. L. Bellinger
Horm Metab Res 1975; 7(2): 132-135

The effects of short term food deprivation on circadian plasma insulin, growth hormone, corticosterone and glucose patterns were studied in male rats. Insulin in the fed controls increased significantly during the latter part of the light phase as previously reported. Insulin in fasted rats also increased significantly during the latter part of the light phase but levels were below fed animals. The late afternoon increase of insulin in fed and fasted animals was not being driven by the glucose rhythms but plasma glucose appeared responsive to insulin changes. Growth hormone and prolactin were significantly elevated in fasting animals during part of the day as compared to fed animals. Corticosterone patterns were similar in fed and fasted animals.

Rat - Fasting - Insulin - Growth Hormone - Prolactin - Corticosterone - Glucose
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Nelson Vergel

Reviews in Endocrine and Metabolic Disorders
pp 1-16

First online: 05 November 2015

The role of prolactin in andrology: what is new?

Giulia Rastrelli, Giovanni Corona, Mario Magg


Prolactin (PRL) has been long deemed as a hormone involved only in female reproduction. However, PRL is a surprising hormone and, since its identification in the 1970s, its attributed functions have greatly increased. However, its specific role in male health is still widely unknown. Recently, low PRL has been associated with reduced ejaculate and seminal vesicle volume in infertile subjects. In addition, in men consulting for sexual dysfunction, hypoprolactinemia has been associated with erectile dysfunction and premature ejaculation, findings further confirmed in the general European population and infertile men. Several metabolic derangements, recapitulating metabolic syndrome, have also been associated with low PRL both in men with sexual dysfunction and from the general European population. In men with sexual dysfunction, followed-up for more than 4 years, low PRL was identified as an independent predictor of the incidence of major adverse cardiovascular events. Finally, an association with anxiety or depressive symptoms has been found in men with sexual dysfunction and from the general European population. While a direct role for impaired PRL function in the pathogenesis of these reproductive, sexual, metabolic and psychological disorders is conceivable, the possibility that low PRL is a mirror of an increased dopaminergic or a decreased serotonergic tone cannot be ruled-out. Hyperactivity of the dopaminergic system can explain only a few of the aforementioned findings, whereas a hypo-serotonergic tone fits well with the clinical features associated with low PRL, and there is significant evidence supporting the hypothesis that PRL could be a mirror of serotonin in the brain.

Message: Be careful with over-treating prolactin!

Nelson Vergel

Cabergoline Tapering Is Almost Always Successful in Patients With Macroprolactinomas

Patients with macroprolactinomas require treatment for two main reasons: to reverse the deleterious consequences of hyperprolactinemia [1] and to reduce tumor mass effects [2]. Cabergoline (CAB) is currently the dopamine agonist (DA) of choice in this setting [3, 4], having been found to be more effective than other DAs [5]. In a compilation of data from 14 prospective studies of CAB in patients with hyperprolactinemic disorders, the hormonal response rate was 73% to 96%, and tumor size was reduced in 50% to 100% of patients [5]. CAB is also better tolerated, with less nausea and dizziness [6], and treatment adherence is improved by the once-per-week dosing schedule. In general, prolactin (PRL) levels are normalized by a low weekly CAB dose of 0.5 to 1 mg [5]. According to Endocrine Society guidelines, once the PRL level has normalized and tumor volume has decreased, DA therapy should be continued for a minimum of two years [4]. Between 24% and 75% of patients maintain a normal PRL level after DA withdrawal. Two meta-analyses suggest that remission persists after CAB withdrawal in about one-third of patients, on average.

Nelson Vergel

Med Sci Monit. 2018 Sep 29;24:6900-6909. doi: 10.12659/MSM.909970.

Lack of Relationships Between Serum Prolactin Concentrations and Classical Cardiovascular Risk Factors in Eastern Croatian Older Adults

Bekić S1, Šabanović Š1, Šarlija N2, Bosnić Z1, Volarić N3, Majnarić Trtica L1,3.

BACKGROUND Relationships between serum prolactin concentrations and various CV risk factors in older adults have rarely been assessed. The aim of this study was to examine the relationships between serum prolactin concentrations and CV risk factors in older patients with multiple CV risk factors. MATERIAL AND METHODS This case-control study included 92 patients, 50-89 years old (median, 69 years), with multiple CV risk factors. We used data from general practice electronic health records and biochemical laboratory tests. Patients were divided according to categories of CV risk factors. RESULTS Serum prolactin concentrations were significantly higher in elderly people (£65 vs. >65) and in men (70.65±58.02 vs. 150.82±114.05 mIU/L), as well as in patients with lower renal function (156.70±127.23 vs. 72.53±37.25 mIU/L, the bottom vs. top quartile of creatinine clearance), higher serum homocysteine and TSH concentrations, and in those who used NSAID and statins. Parameters indicating chronic inflammation (CRP) and renal function decline (creatinine clearance) were significantly and independently correlated with increased serum prolactin concentrations in multiple regression analysis. CONCLUSIONS When assessing the relationships between prolactin and CV risk factors in older people with multiple CV risk factors, the effect of renal function decline and chronic inflammation should receive attention.

Nelson Vergel

Shutting down prolactin impairs the increase of testosterone caused by hCG.

Effects of chronic bromocriptine-induced hypoprolactinemia on plasma testosterone responses to human chorionic gonadotropin stimulation in normal men

Oseko, Fumimaro ; Nakano, Akinobu ; Morikawa, Keiko ; Endo, Jiro ; Taniguchi, Ataru ; Usui, Tuguru
Fertility and Sterility, February 1991, Vol.55(2), pp.355-357

To study the role played by normal levels of plasma prolactin (PRL) in the secretion of testosterone (T) in the testes, we induced hypoprolactinemia with a daily dose of 5mg bromocriptine administered orally in five normal men 20 to 35years of age for 8weeks. The basal PRL, T, luteinizing hormone, follicle-stimulating hormone, and maximum responses of plasma T to human chorionic gonadotropin (hCG) stimulation were measured every 2weeks. Basal levels of plasma T were reduced in the 1st 2-week-long period of hypoprolactinemia. In the 4-week-long period of hypoprolactinemia, the maximal response of plasma T to hCG stimulation was significantly reduced. The findings suggest that normal levels of plasma PRL may play an important role in the secretion of T in the human testes in vivo.

Nelson Vergel

Prolactin blocks 5 alpha reductase (responsible for DHT production), which may be related to its decreasing effect on libido.

The Effect of Prolactin on Androgen Response to Human Chorionic Gonadotropin in Normal Men
Lackritz, Richard M. ; Bartke, Andrzej
Fertility and Sterility, August 1980, Vol.34(2), pp.140-143

Testicular androgen responses to human chorionic gonadotropin (hCG) were compared in normal males before and after suppression of prolactin (PRL) secretion with bromocriptine. Baseline follicle-stimulating hormone, luteinizing hormone, and PRL levels were suppressed by bromocriptine, 2.5mg daily (P<0.05). Serum testosterone and dihydrotestosterone (DHT) levels were reliably increased by one intramuscular injection of hCG (P<0.05). Although testosterone responses to hCG were not significantly different in normal PRL and suppressed PRL cycles (P>0.05), the DHT response was significantly increased in the suppressed cycle (P<0.05), suggesting a physiologic 5α-reductase blockage by PRL in men.

Nelson Vergel


Nelson Vergel


Nelson Vergel

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