Prolactin causes breasts to grow and develop and causes milk to be made after a baby is born. Normally, both men and women have small amounts of prolactin in their blood. Prolactin levels are controlled by other hormones called prolactin inhibiting factors PIFs , such as dopamine.
During pregnancy, prolactin levels go up. After the baby is born, there is a sudden drop in estrogen and progesterone. High prolactin levels trigger the body to make milk for breastfeeding. In men, prolactin affects sperm production. Hyperprolactinemia is a condition of too much prolactin in the blood of women who are not pregnant and in men.
Hyperprolactinemia is relatively common in women. About a third of women in their childbearing years with irregular periods but normal ovaries have hyperprolactinemia. When this happens, a woman might have trouble getting pregnant or her breasts may start producing milk outside of pregnancy galactorrhea.
Ninety percent of women with galactorrhea also have hyperprolactinemia. High prolactin levels interfere with the normal production of other hormones, such as estrogen and progesterone. This can change or stop ovulation the release of an egg from the ovary.
Klibanski The most commonly cited indications for treatment of microprolactinomas is infertility and hypogonadism. Hypogonadism and infertility associated closely with the treatment: DA agonists can restore normal PRL levels and consequently the normal gonadal function.
Gillam ; Wang Prolactin is under dual regulation by hypothalamic hormones delivered through the hypothalamic—pituitary portal circulation. The differential diagnosis and causes of pathological hyperprolactinemia are summarized in Figure 1.
The predominant signal is inhibitory, preventing prolactin release, and is mediated by the neurotransmitter dopamine. The stimulatory signal is mediated by the hypothalamic TRH. The balance between the two opposite signals determines the amount of prolactin released from the anterior pituitary gland Verhelst; Prolactin is under dual control from the hypothalamus.
The first steps in cases of signs of hyperprolactinemia should be a critical diagnosis, as discussed above, may involve dynamic testings, assessment for macroprolactinemia and further laboratory tests to eliminate false positive or negative results.
The major steps of diagnosis of hyperprolactinemia is summarized in Figure 2. Approach to diagnosis of hyperprolactinemia. Specific recommendations for diagnosis of hyperprolactinemia include the following Melmed :. A single measurement of serum prolactin level can confirm the diagnosis if the level is above the upper limit of normal and the serum sample was obtained without excessive venipuncture stress.
Dynamic testing of prolactin secretion is not recommended to diagnose hyperprolactinemia. When there is a discrepancy between a very large pituitary tumour and a mildly elevated prolactin level, serial dilution of serum samples is recommended to eliminate the "hook effect," or an artifact that can occur with some immunoradiometric assays leading to a falsely low prolactin value.
Specific recommendations for management of drug-induced hyperprolactinemia are as follows Melmed :. In a symptomatic patient with suspected medication-induced hyperprolactinemia, the drug should be discontinued for 3 days or an alternative drug substituted, and the serum prolactin measurement should then be repeated. However, the patient's physician should be consulted before an antipsychotic agent is discontinued or substituted.
If the drug cannot be discontinued and the onset of the hyperprolactinemia does not coincide with starting therapy, magnetic resonance imaging MRI of the pituitary gland may distinguish medication-induced hyperprolactinemia from symptomatic hyperprolactinemia caused by a pituitary or hypothalamic mass. Patients with asymptomatic medication-induced hyperprolactinemia should not be treated.
Estrogen or testosterone can be used in patients with long-term hypogonadism hypogonadal symptoms or low bone mass caused by medication-induced hyperprolactinemia. If it is not possible to stop the drug causing medication-induced hyperprolactinemia, cautious administration of a dopamine agonist should be considered, in consultation with the patient's physician. As noted above, prolactin levels can often be corrected by stopping suspected medication or switching to a different medication type.
Correction of hypothyroidism is also effective and specific to reduce PRL levels. If prolactin levels are persistently high, they can be effectively treated with a group of medications known as dopamine agonists. According to our clinical practice patients with macroadenoma suggested to undergo transsphenoidal pituitary surgery. Medical treatment is given to the subjects with microadenoma, persistent postoperative hyperprolactinemia, and to those cases of hyperprolactinemia when it is caused by other medications.
From the available mediactions Bromocriptine 2. Parlodel is an effective and inexpensive medication for high prolactin levels. Parlodel is usually taken at bedtime with a snack. This is because Parlodel will occasionally cause dizziness or stomach upset, so taking it before sleep and with food will reduce those side effects.
Generally with time, the side effects stop anyway. The prolactin levels can be rechecked in about three weeks. If the levels are still elevated the dose can be increased or a different medication can be tried.
The administration of Parlodel can be stopped upon diagnosis of pregnancy. However, if a woman has a macroadenoma, Parlodel should be continued through pregnancy and delivery. Due to the side effects, some women can not tolerate Parlodel.
For these women, they may try alternatives, e. Because it is more expensive, cabergoline is not usually the first choice for treatment of high prolactin levels. It is usually used when Parlodel is ineffective or a woman cannot tolerate the side effects. Cabergoline is a longer acting medication. It is usually given twice a week instead of every day. The Endocrine Society has released a new clinical practice guideline for the diagnosis and treatment of patients with hyperprolactinemia Melmed, The new recommendations for management of elevated levels of the PRL, which is associated with infertility, low sex drive, and bone loss, are listed.
Dopamine agonist therapy is recommended to reduce prolactin levels and tumor size and to restore gonadal function in patients with symptomatic prolactin-secreting microadenomas or macroadenomas.
Compared with other dopamine agonists, cabergoline is more effective in normalizing prolactin levels and in shrinking pituitary tumours. Dopamine agonists are not recommended for asymptomatic patients with microprolactinomas. However, patients with microadenomas who have amenorrhea can be treated with a dopamine agonist or oral contraceptives.
In patients treated with dopamine agonists for at least 2 years who no longer have elevated serum prolactin levels or visible tumour on MRI, careful clinical and biochemical follow-up therapy may be tapered and perhaps discontinued. Specific recommendations for management of resistant and malignant prolactinoma are as follows Melmed :. For symptomatic patients in whom normal prolactin levels are not achieved or who have significant shrinking of the tumour size while receiving standard doses of a dopamine agonist, the dose should be increased rather than referring the patient for surgery.
Symptomatic patients with prolactinomas who cannot tolerate high doses of cabergoline or who are unresponsive to dopamine agonist therapy should be offered trans-sphenoidal surgery.
Patients intolerant of oral bromocriptine may respond to intravaginal administration. Radiation therapy is recommended for patients in whom surgical treatment fails or for those with aggressive or malignant prolactinomas. Specific recommendations for management of prolactinoma during pregnancy are as follows Melmed :. Women with prolactinomas should discontinue dopamine agonist therapy as soon as pregnancy is recognized, except for selected patients with invasive macroadenomas or adenomas abutting the optic chiasm.
Unless there is clinical evidence for tumour growth, such as visual field impairment, routine use of pituitary MRI during pregnancy is not recommended in patients with microadenomas or intrasellar macroadenomas. Women with macroprolactinomas that do not shrink during dopamine agonist therapy or women who cannot tolerate bromocriptine or cabergoline should be counselled regarding the potential benefits of surgical resection before attempting pregnancy. Bromocriptine therapy is recommended in patients who experience symptomatic growth of a prolactinoma during pregnancy.
Hyperprolactinemia has been proposed to block ovulation through inhibition of GnRH release. Kisspeptin neurons, which express prolactin receptors, were recently identified as major regulators of GnRH neurons. A recently published study demonstrated that hyperprolactinemia in mice induced anovulation, reduced GnRH and gonadotropin secretion, and diminished kisspeptin expression. Kisspeptin administration restored gonadotropin secretion and ovarian cyclicity, suggesting that kisspeptin neurons play a major role in hyperprolactinemic anovulation.
This study indicate that administration of kisspeptin may serve as an alternative therapeutic approach to restore the fertility of hyperprolactinemic women who are resistant or intolerant to dopamine agonists Sonigo, To sum up, the systematic reviews and meta-analyses affirm the use of dopamine agonists in treating hyperprolactinemia and reducing associated morbidity.
Radiotherapy and surgery are efficacious in patients with resistance or intolerance to dopamine agonists Wang, Hyperprolactinemia is defined as higher-than-normal blood levels of the hormone prolactin. This hormone is made by the pituitary gland, which is located at the base of the brain. The main function of prolactin is to stimulate breast milk production after childbirth.
High prolactin levels are normal during pregnancy and breastfeeding. In other cases, prolactin can become too high because of a disease or the use of certain medications.
Often, the cause is a prolactin-producing tumour in the pituitary gland, called a prolactinoma. It is more common in women than men. Rarely, children and adolescents develop prolactinomas. Other brain tumours may also cause the pituitary gland to make too much prolactin. Prolactin-secreting pituitary tumours are a common cause of amenorrhea and infertility in premenopausal women.
The goals of therapy are to normalize prolactin, restore gonadal function and fertility, and reduce tumour size, and dopamine agonists are the preferred therapy. Clinically significant tumour enlargement during pregnancy is uncommon and dependent on tumour size and pre-pregnancy treatment.
At our institution patients with symptomatic prolactinomas, both micro- and macroadenomas, are treated with cabergoline as the first-line approach. In the small group of patients who do not respond to this treatment, or who refuse long-term therapy, surgery is offered.
Radiotherapy is given if both pharmacologic therapy and surgery fail. Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3. Help us write another book on this subject and reach those readers. Login to your personal dashboard for more detailed statistics on your publications. Edited by Alemayehu Lemma. We are IntechOpen, the world's leading publisher of Open Access books. Built by scientists, for scientists.
Our readership spans scientists, professors, researchers, librarians, and students, as well as business professionals. Downloaded: Introduction Prolactin PRL is one of several hormones that are produced by the pituitary gland.
Yu-lee ; Bachelot During the first several months of breastfeeding, the higher basal prolactin levels also serve to suppress ovarian cyclicity, through the inhibition of pituitary hormones, mainly via LH suppression Taya This is the reason why women who are breastfeeding do not get their periods and therefore do not often become pregnant.
Baird Similarly, elevated PRL levels are shown during gestation, but mechanisms to inhibit ovulation is related to elevated estardiol and progesterone levels and a consequent depression of pituitary FSH secretion Marrs Binart On the other hand, high prolactin levels are associated with anovulation or may cause directly or indirectly infertility.
Adenomas larger than 1 centimeter are called macroadenomas. If untreated, macroadenomas can grow larger and start to push on nearby structures. The closest structures are the optic nerves. If a macroadenoma causes compression of the optic nerves, partial blindness can result. Medication can be used to treat them but if that fails, surgery may be necessary. If a woman has an underactive thyroid gland, a portion of the brain called the hypothalamus will secrete hormones to try to stimulate the thyroid gland.
This same hormone may also cause excess prolactin to be produced from the pituitary. Treatment with thyroid hormone supplements will result in correction of both the thyroid and the high prolactin levels.
PCOS is a common problem that can cause infertility by inhibiting ovulation. For unknown reasons, some women with PCOS may have slightly high prolactin levels. Some medications can cause higher levels of prolactin to be produced. The most common medications that do this are known as anti-psychotic medications. Other medications which may increase prolactin levels:.
A high prolactin level can sometimes be due to physical stress. Even drawing blood can by itself cause someone to produce to much prolactin. As noted above, prolactin levels can often be corrected by stopping or switching to a different medication. Correction of hypothyroidism is very effective also.
If prolactin levels are persistently high, they can be effectively treated with a group of medications known as dopamine agonists. Parlodel is an effective and inexpensive medication for high prolactin levels. Parlodel is usually taken at bedtime with a snack. This is because Parlodel will occasionally cause dizziness or stomach upset.
The prolactin levels can be rechecked in about three weeks. If the levels are still elevated the dose can be increased or a different medication can be tried. The Parlodel can be stopped upon diagnosis of pregnancy. However, if a woman has a macroadenoma, Parlodel should be continue through pregnancy and delivery.
Due to the side effects, some women cannot tolerate Parlodel. For these women, they may try inserted the pills vaginally instead of taking them orally. Because it is more expensive, cabergoline is not usually the first choice for treatment of high prolactin levels. It is usually used when Parlodel is ineffective or a woman cannot tolerate the side effects. Cabergoline is a longer acting medication. It is usually given twice a week instead of every day. See in Google Maps. Skip to content.
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