Most things in life take a little work to get going. If you want to start your car, you first need to fuel up and turn on the engine. Similarly, in order to power your body, you have to eat something first. However, one of the few things in the human body that defaults to the “on” position is… lactation! (It’s true: even moderately malnourished mothers will still lactate effectively.) If you are not currently pregnant or breastfeeding, prolactin levels are typically low as the body holds down the “off” switch for lactation to prevent unnecessary milk production. But in some cases, prolactin, the hormone responsible for aspects of breast tissue development and lactation, is at higher levels than normal. This is called hyperprolactinemia. Here I’ll cover symptoms and causes of hyperprolactinemia, along with whether hyperprolactinemia may be a sign of cancer.
Symptoms of hyperprolactinemia
Excess levels of prolactin can cause infertility, low sex drive, low bone mass, and nipple secretions. While these might be normal symptoms for someone who has just had a baby, in hyperprolactinemia these symptoms occur separate from pregnancy or breastfeeding.
Even more unusual? Hyperprolactinemia can occur in both women and men. For women, high prolactin is also associated with having irregular or absent periods and vaginal dryness. For men, high prolactin is also associated with erectile dysfunction, low testosterone, and enlarged breast tissue.
Is hyperprolactinemia common?
According to an article published in the Journal of Human Reproductive Sciences, while the prevalence of hyperprolactinemia in the general population is very low (around 0.4%), the prevalence in women with reproductive diseases ranges from 9-17%. The high side of the range, 17%, is specifically the prevalence for women with polycystic ovary syndrome (PCOS). For patients seeking infertility treatment, the prevalence is around 5% [1].
So, while hyperprolactinemia is rather rare, its higher prevalence amongst women experiencing other reproductive issues may give clues to the relationship between prolactin and other fertility-related hormones.
Is hyperprolactinemia a sign of cancer?
Hyperprolactinemia is most commonly caused by a benign (non-cancerous) tumor on the pituitary gland called a prolactinoma (more on these in a bit) [1]. Recent research links high prolactin levels with autoimmune diseases, listed below [2][3].
A high level of prolactin on its own is not an indication of cancer. However, individuals with sustained high prolactin levels are at increased risk of developing cancer, particularly breast cancer. In this 2017 journal article in Endocrinology, the authors explain how prolactin interacts with many different organ systems, and how prolactin affects changes in the breasts, pancreas, adipose (fat) tissue, liver, and endometrium to prepare the body for pregnancy [4].
Outside of pregnancy, elevated prolactin can cause cells to proliferate at a time when this is not needed. This may cause or exacerbate tumor growth. Elevated prolactin has been implicated in breast, ovarian, prostate, liver, colon, and endometrial cancers, amongst others, hence the importance of identifying and treating hyperprolactinemia early on [4].
Causes of hyperprolactinemia
Because the pituitary gland produces prolactin, hyperprolactinemia indicates a problem with the hypothalamic-pituitary-adrenal axis (HPA axis). The HPA axis is how the nervous system and endocrine system work together to regulate different body systems in response to stress.
Prolactinomas
Prolactinomas, or small benign tumors on the pituitary gland, are the most common cause of hyperprolactinemia [1]. They’re responsible for about 50% of cases of hyperprolactinemia [1]. According to Cleveland Clinic, prolactinoma symptoms include headaches, nausea, vision problems, and sinus problems. According to the National Institute of Health, prolactinomas can be treated very effectively with a class of medicine called dopamine agonists.
How are dopamine and prolactin connected? Dopamine, a neurotransmitter (chemical messenger in the brain), suppresses prolactin. Activating dopamine receptors therefore counteracts the prolactinoma. Surgery is an available treatment for patients who cannot take dopamine agonists or who wish to treat their tumor more quickly in order to attempt to become pregnant.
Endocrine diseases and chest wall injuries
Additionally, diseases that affect the endocrine system can lead to hyperprolactinemia. These include hypothyroidism (underactive or low thyroid), PCOS, Cushing’s Syndrome (when cortisol, the stress hormone, levels are too high), or kidney disease. Injuries to the chest wall, including shingles affecting the chest area, can also temporarily increase prolactin levels.
In cases of other illness or injury impacting prolactin levels, the treatment is to address the underlying cause of hyperprolactinemia and then reevaluate prolactin levels.
Endometriosis and hyperprolactinemia
Hyperprolactinemia is also associated with stage III and stage IV endometriosis. This 2019 study even suggested that prolactin levels could be used to detect advanced endometriosis [3]. However, there are limited studies that explore the relationship between endometriosis and prolactin levels. Furthermore, their results are controversial. Hopefully, further research will help us to better understand the mechanisms of both diseases [3].
Autoimmune disease
This 2018 study summarized the research on the connection between hyperprolactinemia and many autoimmune diseases, including rheumatoid arthritis, anti-phospholipid syndrome, thyroid disease (which has both endocrine and autoimmune aspects), multiple sclerosis, systemic sclerosis, peripartum cardiomyopathy, and lupus [2]. Additionally, endometriosis is increasingly believed to have an autoimmune component [3]. While high prolactin may occur at the same time as various autoimmune diseases, further research is needed to confirm whether high prolactin is the metaphorical chicken or the egg.
Medications and birth control
Since dopamine helps to hold down the “off” button on prolactin, medications that disrupt dopamine can also lead to too-high prolactin levels. These can include high blood pressure medication, antipsychotics, anti-nausea medicine, heartburn medication, opioids, and menopause treatment that includes estrogen. If hyperprolactinemia is a problematic side effect of your medication, working with your doctor to find a different treatment plan or discontinuing the medication should resolve elevated prolactin levels.
Birth control pills can also cause high prolactin levels. How? The Pill contains high levels of synthetic estrogen. When a woman takes the Pill, her body’s own production of estrogen is inhibited, which decreases her dopamine levels. This may help explain why hormonal birth control use is associated with a greater risk of experiencing depression. Individuals with depression tend to have lower levels of dopamine compared to those without depression. If the Pill might be causing your prolactin problem, check out our resources for getting off the Pill here!
The bottom line on hyperprolactinemia
The good news with hyperprolactinemia is that the prognosis is generally good. For the bulk of cases, tumor-related hyperprolactinemia can be easily treated with medication. For medication-related hyperprolactinemia, medication can potentially be stopped or changed to manage unwanted side-effects. For high prolactin levels related to underlying hormonal issues, the path may be more complex, but working with an endocrinologist or a medical professional who practices Restorative Reproductive Medicine can help you to tackle your different conditions as a whole to restore whole-body health and effectively treat one of the various causes of infertility and irregular cycles.
References:
[1] Majumdar A, Mangal NS. Hyperprolactinemia. J Hum Reprod Sci. 2013 Jul;6(3):168-75. doi: 10.4103/0974-1208.121400. PMID: 24347930; PMCID: PMC3853872. [2] Borba VV, Zandman-Goddard G, Shoenfeld Y. Prolactin and Autoimmunity. Front Immunol. 2018 Feb 12;9:73. doi: 10.3389/fimmu.2018.00073. PMID: 29483903; PMCID: PMC5816039. [3] Mirabi P, Alamolhoda SH, Golsorkhtabaramiri M, Namdari M, Esmaeilzadeh S. Prolactin concentration in various stages of endometriosis in infertile women. JBRA Assist Reprod. 2019 Aug 22;23(3):225-229. doi: 10.5935/1518-0557.20190020. PMID: 30969738; PMCID: PMC6724390. [4] Felicitas Lopez Vicchi , Damasia Becu-Villalobos, Prolactin: The Bright and the Dark Side, Endocrinology, Volume 158, Issue 6, 1 June 2017, Pages 1556–1559, https://doi.org/10.1210/en.2017-00184Additional Reading:
‘Adrenal fatigue’ may not be real, but HPA axis dysfunction definitely is
5 causes of infertility that (almost) no one talks about
The link between depression and birth control
Getting to know synthetic estrogens and progestins: What do they do to our bodies?
Have you seen a connection between low B6 and/or folate and elevated serum prolactin?
Hi Tracy, The only research we’re aware of on Vitamin B6 and high prolactin levels is this. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426548/ It shows that high prolactin levels were decreased by Vitamin B6 supplementation in men whose hyperprolactinemia was caused by antipsychotics.