By Cristina Mestre Ferrer BSc, MSc (embryologist).
Last Update: 07/09/2014

Prolactin (PRL) is a hormone secreted by the hypophysis that stimulates colostrum production and breast milk secretion by the mammary glands, thus allowing breastfeeding. This hormone is also involved in the synthesis of progesterone during the luteal phase of the menstrual cycle.

The different sections of this article have been assembled into the following table of contents.

Definition

A recurrent pathology related to the hormone prolactin is hyperprolactinemia, characterized for being an increase of blood prolactin. Female normal prolactin rate is about 20 µg/l. We talk about hyperprolactinemia when the value is higher than 30 µg/l.

These abnormal hormone blood levels can alter ovulation, the menstrual cycle, and eventually lead to infertility.

Anovulation as a consequence of high levels of prolactin is the most prevalent cause of female infertility. In 80% of cases, ovulation can be improved 6 months after undergoing a pharmaceutical treatment (with dopaminergic agonists).

Causes

There are several physiological situations throughout a woman’s life that may cause a transitory increase of blood prolactin, like in the luteal phase of the menstrual cycle, during gestation and while breastfeeding.

A transitory increase of blood prolactin may also occur during slow-wave sleep, physical exercise, orgasm, mammary manipulation or nipple stimulation, and under stressful situations.

There are iatrogenic causes as well which consist of external factors such as the consumption of neuroleptics, antidepressants, anxiolytics, tranquilizers or opiates (morphine derivatives). These drugs decrease the action and synthesis of dopamine. Dopamine inhibits prolactin, so a decrease in dopamine invariably leads to an increase in blood prolactin.

Oral contraceptive pills with estrogens produce a mild increase in blood prolactin.

The most common pathological causes that may cause this disorder are: hypothyroidism, hyperandrogenism (androgen excess), nervous anorexia, chronic renal insufficiency, polycystic ovary syndrome (PCOS), repeated psychological stress…

Sometimes, hyperporlactinemia can be a consequence of a benign tumor, like hypophyseal adenomas. Amongst these hypophyseal tumors, prolactinomas are the most common type, covering 30% of the cases.

Symptoms

Not every patient presents all the symptoms listed, some only present the most common ones:

  • Galactorrhea, i.e. secretion of milk through the mammary glands (30% of the cases).
  • Primary or secondary amenorrhea, absence of menstruation.
  • Headaches and alterations in the field of vision due to tumors.
  • Hirsutism, if there is a hyperandrogenism.
  • Osteoporosis, if there is a hypogonadism.
  • Decreased libido.
  • Infertility.

Diagnosis

The first diagnostic test in every patient with potential hyperprolactinemia will be the determination of the prolactin blood levels between the 3rd and 5th day of the menstrual cycle. The test will be conducted twice to confirm the diagnosis.

To determine what is causing hyperprolactinemia, the clinical history will be evaluated and an anamnesis and an exhaustive physical examination will be carried out to rule out possible causes such as pregnancy, use of estrogens (oral contraceptive pill) or anxiolytic, antidepressants drugs…

If the patient presents hyperprolactinemia and is not linked to hypothyroidism, the presence of a hypophyseal tumor must be ruled out by means of a computerized axial tomography (CAT) or through a nuclear magnetic resonance (NMR).

Treatment

When dealing with hyperprolactinemia, the cause of such increase of blood prolactin must be identified.

If the situation is caused by the consumption of drugs, ceasing the consumption may restore the condition, therefore going back to normal prolactin levels. If it is induced by hypogonadism , a replacement treatment using thyroid hormones reduces the blood levels.

When there is a hypophyseal adenoma or prolactinoma, the treatment contemplates the administration of bromocriptine (a dopaminergic agonist), that has the same neurotransmission effect than dopamine.

After six months of treatment with bromocriptine, ovulatory menstrual cycles are restored to its normal levels, therefore improving fertility, provided that there aren’t associated factors.

Sometimes the size of a prolactinoma advises the use of surgery, although it does not assure the prolactinoma to not come back again, thus forcing the beginning of a new treatment, as the prolactin levels have not been restored, either the fertility.

Radiotherapy can also be used, although is less used since it requires a longer treatment to reinstate normal prolactin levels.

A pharmaceutical approach aimed to restore prolactin levels and fertility as soon as possible (specially among young patients), will be the therapeutical treatment of choice.

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Authors and contributors

 Cristina Mestre Ferrer
BSc, MSc
Embryologist
Bachelor's Degree in Biological Sciences, Genetics & Human Reproduction from the University of Valencia (UV). Master's Degree in Biotechnology of Human Assisted Reproduction from the UV and the Valencian Infertility Institute (IVI). Embryologist at IVI Barcelona. More information
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