Patient education: High prolactin

levels and prolactinomas (Beyond

the Basics) - UpToDate
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Patient education: High prolactin levels and prolactinomas

(Beyond the Basics)

Author:
Peter J Snyder, MD
Section Editor:
David S Cooper, MD
Deputy Editor:
Kathryn A Martin, MD

Contributor Disclosures

Literature review current through: Nov 2019. | This topic last

updated: Sep 06, 2019.

HIGH PROLACTIN OVERVIEW

The pituitary is a small gland in the middle of the head just below the

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 brain (figure 1). The pituitary contains lactotroph cells that produce
prolactin, the hormone that stimulates lactation (production of breast
milk).

Prolactinomas (also called "prolactin-producing adenomas" or

"lactotroph adenomas") are benign (non-cancerous) tumors of the
pituitary gland that produce prolactin, thereby causing higher than
normal blood prolactin concentrations. They can cause symptoms,
either when the high blood prolactin concentration interferes with the
function of the ovaries or testicles or, less commonly, when the
adenoma grows large enough to compress the pituitary gland or
nearby structures in the head, such as the nerves to the eyes.

Prolactinomas occur in both men and women but are more commonly
diagnosed in women who are less than 50 years than in older women
or men.

Prolactinomas can usually be treated successfully with medication

alone. Medication lowers the prolactin level in the blood substantially,
often to normal, and also usually reduces adenoma size. However, a
minority of these adenomas do not respond to medication and must
be treated with surgery or, less commonly, radiation therapy.

CAUSES OF HIGH PROLACTIN

Prolactinomas develop when one of the normal prolactin-producing

cells in the pituitary gland develops a mutation. The mutation allows
the cell to divide repeatedly, resulting in a large number of cells that
produce an excessive amount of prolactin. Approximately 10 percent
produce growth hormone as well as prolactin.

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 Most prolactinomas occur sporadically, but rarely, they occur in
families as part of a condition called the multiple endocrine neoplasia
type 1 (MEN1) syndrome.

Most prolactinomas remain small, less than 1 centimeter (0.4 inches)

in diameter; these are called microadenomas. A minority grow larger,
occasionally to several centimeters, and are called macroadenomas.

SYMPTOMS

The symptoms of prolactinomas fall into two categories: those that

result from elevated blood prolactin levels, and those that result from
compression of the normal pituitary and surrounding tissues.

Symptoms caused by elevated blood prolactin — Elevated blood

prolactin interferes with the secretion of the hormones from the
pituitary gland that control the function of the ovaries in women and
the testicles in men. Therefore, it causes symptoms in premenopausal
women and in men, but not in women who have already been through
menopause, since their ovaries have already stopped functioning.

Women — When a high blood prolactin concentration interferes with

the function of the ovaries in a premenopausal woman, secretion of
estradiol (the main female sex hormone [estrogen] in women)
decreases. Symptoms include irregular or absent menstrual periods,
infertility, menopausal symptoms (hot flashes and vaginal dryness),
and, after several years, osteoporosis (thinning and weakening of the
bones). High prolactin levels can also cause milk discharge from the
breasts.

Men — When a high blood prolactin concentration interferes with the

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 function of the testicles, the production of testosterone (the main male
sex hormone), and sperm production. Low testosterone causes
decreased energy, sex drive, muscle mass and strength, and blood
count (anemia). If levels remain low for several years, bone strength
may decrease (osteoporosis). High levels of prolactin in the blood also
cause difficulty in getting an erection, as well as breast tenderness
and enlargement.

Symptoms caused by compression of surrounding tissue — Large

adenomas can cause symptoms by pressing on nearby structures in
the head. Pressure on nerves to the eyes can impair vision, especially
peripheral (side) vision. Pressure on the pituitary gland can decrease
production of the hormones that stimulate the thyroid gland and
adrenal glands, leading to underactivity of the those glands. Pressure
can also cause headaches.

DIAGNOSIS OF PROLACTINOMA

A prolactinoma is diagnosed based upon an elevated blood level of

prolactin and evidence of a mass in the pituitary gland, as seen by
magnetic resonance imaging (MRI). Because other conditions can
cause an elevated prolactin level, those potential causes must be
evaluated as well.

Measurement of prolactin — The prolactin level can be measured in

a single blood sample. The result can range from slightly elevated to a
thousand times the upper limit of normal. In general, larger adenomas
cause higher prolactin levels.

Magnetic resonance imaging (MRI) — MRI is the best test for

identifying masses in or near the pituitary gland, although MRI cannot

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 determine if the mass is a pituitary adenoma or another abnormality.
Furthermore, some small adenomas (microadenomas) cannot be
detected by MRI, and not all adenomas secrete prolactin or other
hormones.

Evaluating other causes — Some of the medications that are used to

treat psychiatric conditions can cause high blood prolactin levels.
Other causes of high prolactin include female sex hormones
(estrogens; if taken by mouth) and underactivity of the thyroid gland
(hypothyroidism).

PROLACTINOMA TREATMENT OPTIONS

The goals of treatment are to lower the level of prolactin in the blood
to normal and to decrease the size of a large adenoma, especially if it
is compressing surrounding structures. It is important that the clinician
and patient discuss the possible benefits and risks of treatment.

Not all prolactinomas require treatment. If the tumor is large or causing

symptoms, it should probably be treated, but if it is small and is not
causing symptoms, it does not need to be treated.

When treatment is necessary, most prolactinomas respond well to

therapy with medications called dopamine agonists. If an adenoma
does not respond to any of these medications or if the medication
causes intolerable side effects, other treatments should be
considered.

MEDICATIONS TO TREAT PROLACTINOMAS

A dopamine agonist is the best first treatment for a prolactinoma of

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 any size. Two dopamine agonists are currently available for this
purpose in the United States, cabergoline and bromocriptine; another
one, quinagolide, is also available in other countries.

●Bromocriptine – Bromocriptine has been used for many years to

treat prolactinomas. It is taken twice a day. While it is usually very
effective in lowering blood prolactin levels, it can cause side effects,
including dizziness, nausea, and nasal stuffiness. Many of the side
effects can be avoided by taking the medication with meals or at
bedtime and by starting with a very low dose. Bromocriptine may be a
better choice of dopamine agonist for restoring fertility in women who
want to become pregnant. (See 'Becoming pregnant' below.)

●Cabergoline – Cabergoline is taken once or twice a week and is

much less likely to cause nausea compared with other dopamine
agonists. It may be effective for treating prolactinomas that are
resistant to bromocriptine. For all these reasons, cabergoline is the
best first choice, with the possible exception of women who are trying
to become pregnant.

Effectiveness of dopamine agonists — Dopamine agonists are very

effective for decreasing prolactin levels and the size of most
prolactinomas. Cabergoline, which appears to be the most effective
dopamine agonist, lowers prolactin levels in approximately 90 percent
of people who have prolactinomas, often to a normal level. It also
usually decreases the size of micro- and macroadenomas to normal.
Prolactin levels usually fall within the first two to three weeks of
treatment, but detectable decreases in adenoma size take more time,
usually several weeks to months. When the adenoma affects vision,
improvement in vision may begin within days of starting treatment.

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 If the prolactin level decreases to normal or near-normal levels, the
symptoms caused by the elevated prolactin are reversed. The upper
normal value for serum prolactin in most laboratories is approximately
20 ng/mL (20 mcg/L SI units). In premenopausal women, ovarian
function returns, estradiol levels increase, menstrual periods return to
normal, and fertility returns. In men, testicular function returns,
causing an increase in energy, sex drive, muscle mass, blood count,
and bone calcium. The ability to have an erection returns and,
eventually, breast enlargement regresses.

Side effects of drug therapy — The most common side effects of

dopamine agonists are nausea, lightheadedness after standing, and
mental fogginess. These side effects are most likely to occur when
treatment first begins and when the dose is increased. They can be
minimized by starting with a small dose, increasing the dose slowly if
needed, using small doses more frequently, and taking the drug with
food or at bedtime. Women who still have trouble tolerating their
medication may try taking the pills intravaginally (by inserting them
into the vagina) rather than by mouth. This might decrease or prevent
nausea. However, it is best to talk with a doctor or nurse before trying
this.

Cabergoline has been associated with valvular heart disease in people

with Parkinson disease who took much larger doses than those
typically used to treat prolactinomas. So far, the lower doses used to
treat high blood prolactin are not known to cause heart valve defects.
However, experts recommend using the lowest dose of cabergoline
necessary to lower prolactin to normal; they also recommend doing
ultrasound (echocardiogram) of the heart valves in people with
prolactinomas who need higher than usual doses of cabergoline. Heart

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 valve problems have not been seen in people taking bromocriptine,
even in high doses.

Treatment with dopamine agonists, even at appropriate doses,

increases the risk of impulse control disorders, such as pathologic
gambling or compulsive sexual behavior, shopping, or eating.
Decreasing or discontinuing the dopamine agonist quickly resolves
these behaviors in nearly all cases.

How long is medication needed? — If the prolactin level remains

normal and no tumor is seen on magnetic resonance imaging (MRI) for
two or more years, a trial period without medication can be
considered. However, the high prolactin level often recurs after the
medication is stopped. Monitoring of the prolactin level and, less
frequently, the size of the pituitary, would continue during this time. If
the prolactin levels begin to rise or the adenoma grows in size, a
dopamine agonist should be resumed.

If the dopamine agonist is not effective in lowering the prolactin level,

or if the person cannot tolerate the side effects, surgery to attempt to
remove the adenoma may be considered. (See 'Surgery for
prolactinoma' below.)

Considerations specific to women

Drug therapy and menopause — Women who have microadenomas

usually do not have to continue taking dopamine agonists after
menopause. After menopause, there is no longer a concern about
irregular or absent periods. The prolactin is usually measured a few
months after treatment is stopped to be sure that it is not substantially
higher than before treatment. This is usually done once per year for a

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 few years and less often thereafter. Women who have
macroadenomas should continue taking dopamine agonists after
menopause to keep the size of the adenoma from increasing.

Estradiol and progestin — Estradiol, in combination with a progestin,

is a treatment option for women who have small prolactinomas,
especially women who have intolerable side effects when taking
dopamine agonists and those who do not want to become pregnant.

The rationale for estrogen treatment is that the only known harmful
effect of an elevated blood prolactin in a woman is decreased ovarian
function, including diminished secretion of estradiol. Estradiol doses
and regimen are discussed in a separate topic review. (See "Patient
education: Menopausal hormone therapy (Beyond the Basics)".)

The prolactin concentration should be monitored periodically because

of the small chance that the adenoma could grow. Estradiol and
progestin treatment are not recommended as the only treatment in
women with macroadenomas (>1 cm).

Becoming pregnant — A woman who has a prolactinoma and wants

to get pregnant can usually do so with little risk to herself or her
developing child. However, the woman should speak with an
endocrinology specialist before attempting to become pregnant.
Issues to address include which treatment is best before trying to
conceive, when to discontinue dopamine agonist treatment, the
chance that the adenoma will grow during pregnancy, what would be
done if it does grow, and whether or not breastfeeding is advisable.
These considerations are influenced greatly by whether the adenoma
was less than 1 cm (microadenoma) or greater than 1 cm

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 (macroadenoma) prior to treatment:

●Microadenomas rarely increase in size during the course of

pregnancy. The best treatment to restore fertility in women with a
microadenoma is a dopamine agonist. Bromocriptine does not appear
to increase the risk of miscarriage or birth defects when it is taken to
restore fertility and discontinued early in pregnancy.

Less information is available about the safety of cabergoline, although

the available information does not indicate that it increases the risk of
birth defects. Bromocriptine, therefore, appears to be the safest
dopamine agonist to use to restore fertility, although a woman who has
severe side effects from bromocriptine could reasonably choose
cabergoline. Dopamine agonist treatment should be discontinued as
soon as pregnancy is diagnosed. There is insufficient information
about the safety of these medications during later stages of
pregnancy.

If dopamine agonists do not lower prolactin sufficiently to restore

ovarian function, other medications, such as clomiphene citrate or
gonadotropins, may be recommended to induce ovulation. Once the
woman becomes pregnant, the dopamine agonist should be
discontinued. (See "Patient education: Ovulation induction with
clomiphene (Beyond the Basics)".)

During the course of the pregnancy, it is possible for the prolactinoma

to increase in size. To monitor for an increase in size, the woman
should let her health care provider know if she develops new or
worsening headaches or changes in vision.

●Macroadenomas may increase in size during the course of

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 pregnancy. Signs that the adenoma is growing include new or
worsening headaches or changes in vision.

If vision worsens, the woman should see an ophthalmologist (eye

doctor). An MRI may be recommended to determine if the
prolactinoma has grown. If so, bromocriptine or cabergoline is usually
recommended to decrease the size. There is little information about
the effect of either medication on the fetus during the second and
third trimesters; however, the available information suggests that
neither harms the fetus. If necessary, surgery to remove the adenoma
can be performed during the second trimester.

If the adenoma was greater than 2 cm in diameter or was affecting

vision prior to treatment, surgery should be considered before the
woman tries to become pregnant. Surgery is recommended because
growth of the adenoma during pregnancy can potentially interfere with
vision. Following surgery, a dopamine agonist may be recommended
to restore fertility. Alternatively, if the adenoma is very sensitive to
cabergoline or bromocriptine, a low dose can be continued during the
entire pregnancy or it can be administered only if the adenoma
increases sufficiently to cause visual symptoms during the pregnancy.
(See 'Surgery for prolactinoma' below.)

Breastfeeding — If a woman wishes to breastfeed, she should not

resume dopamine agonist treatment until breastfeeding is completed,
because lowering the prolactin could decrease lactation and because
the infant could be exposed to the medication in the milk. If there was
an increase in the size of the adenoma during pregnancy sufficient to
cause visual symptoms, most experts recommend that the woman not
breastfeed, so that she may restart dopamine agonist treatment

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 immediately after delivery.

SURGERY FOR PROLACTINOMA

Surgery is an option when dopamine agonists are ineffective or not

tolerated. Surgery may also be the best choice for a woman with very
large macroadenoma that is not entirely responsive to dopamine
agonists who wants to become pregnant, because dopamine agonists
must be discontinued during pregnancy, and during this time the
adenoma may grow.

During surgery, a small incision is made in the nose (figure 2). The
incision is extended through the sphenoid sinus, allowing the surgeon
to visualize and remove the adenoma. Most experienced pituitary
neurosurgeons now perform this procedure using an endoscope (a
thin, lighted tube with a camera).

Surgery can often reduce the blood prolactin concentration,

sometimes to normal. This is more likely for a microadenoma than a
macroadenoma. Even if the prolactin is lowered to within the normal
range shortly after surgery, the level may become elevated in the next
several years. Potential side effects of surgery include worsening of
vision, hemorrhage, and meningitis, which are all uncommon, and
hormonal deficiencies. The risk of complications is less when the
procedure is performed by a surgeon who has had significant
experience operating on the pituitary gland.

Radiation therapy — Radiation therapy can shrink prolactinomas and

lower blood prolactin levels, but these effects usually take several
years. Therefore, radiation is uncommonly used as treatment of
macroadenomas, and when it is, it is used to prevent regrowth of

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 substantial residual tissue that could not be removed during surgery of
a macroadenoma that is not responsive to dopamine agonists.

The possible side effects of radiation treatment include temporary

nausea, fatigue, loss of taste and smell, and loss of hair on specific
parts of the scalp. Approximately half of all people who receive
pituitary radiation therapy develop pituitary hormone deficiencies
within 10 years.

WHERE TO GET MORE INFORMATION

Your health care provider is the best source of information for

questions and concerns related to your medical problem.

This article will be updated as needed on our website

(www.uptodate.com/patients). Related topics for patients, as well as
selected articles written for health care professionals, are also
available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient

education materials.

The Basics — The Basics patient education pieces answer the four or
five key questions a patient might have about a given condition. These
articles are best for patients who want a general overview and who
prefer short, easy-to-read materials.

Patient education: Prolactinoma (The Basics)

Patient education: Pituitary adenoma (The Basics)
Patient education: Panhypopituitarism (The Basics)

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 Beyond the Basics — Beyond the Basics patient education pieces are
longer, more sophisticated, and more detailed. These articles are best
for patients who want in-depth information and are comfortable with
some medical jargon.

Patient education: Menopausal hormone therapy (Beyond the Basics)

Patient education: Ovulation induction with clomiphene (Beyond the
Basics)

Professional level information — Professional level articles are

designed to keep doctors and other health professionals up-to-date
on the latest medical findings. These articles are thorough, long, and
complex, and they contain multiple references to the research on
which they are based. Professional level articles are best for people
who are comfortable with a lot of medical terminology and who want
to read the same materials their doctors are reading.

Causes of hyperprolactinemia
Causes, presentation, and evaluation of sellar masses
Clinical manifestations and evaluation of hyperprolactinemia
Management of lactotroph adenoma (prolactinoma) during pregnancy
Incidentally discovered sellar masses (pituitary incidentalomas)
Management of hyperprolactinemia

The following organizations also provide reliable health information.

●National Library of Medicine

(www.nlm.nih.gov/medlineplus/healthtopics.html)

●National Institute of Diabetes and Digestive and Kidney Disorders

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 (www.niddk.nih.gov/)

●Hormone Health Network

(http://www.hormone.org/diseases-and-
conditions/pituitary/hyperprolactinemia)

●Pituitary Network Association

(www.pituitary.org)

Topic 2182 Version 14.0

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