INTRODUCTION — Lactotroph adenomas (prolactinomas) usually cause infertility because of the inhibitory effect of elevated prolactin, and sometimes because of the mass effect of a macroadenoma, on gonadotropin secretion, resulting in anovulation and decreased estradiol and progesterone secretion. However, our ability to treat both of these abnormalities allows most women with this disorder to become pregnant. Management during pregnancy is based on knowledge of the risks to the mother and the fetus.

The management of women with lactotroph adenomas during pregnancy will be reviewed here. Other aspects of hyperprolactinemia and lactotroph adenomas are reviewed separately. (See "Clinical manifestations and evaluation of hyperprolactinemia" and "Causes of hyperprolactinemia" and "Management of hyperprolactinemia".)

OVERVIEW — Most women with lactotroph adenomas have anovulatory infertility and even frank hypogonadism but are able to conceive once the lactotroph adenoma has been treated and the serum prolactin concentration has been lowered to normal. Management should begin before lowering the prolactin concentration with a discussion about the risks of adenoma growth during pregnancy and the potential effects of exposure to dopamine agonists on the fetus. Current data suggest that neither bromocriptine nor cabergoline use during the first month of pregnancy harms the fetus. However, few data are available about the risk of either drug later in pregnancy.

Goals of treatment — The main goals of treatment for women with lactotroph adenomas considering pregnancy include:

●Women with microadenomas – Lower serum prolactin into the normal range to allow spontaneous ovulation.

●Women with macroadenomas – Administer dopamine agonists or perform transsphenoidal surgery to decrease adenoma size before attempting to conceive.

●During pregnancy, monitor women for possible adenoma growth; growth that affects visual function should be treated with dopamine agonists or, if necessary, surgery (but only in the second trimester).

PATIENT COUNSELING BEFORE PREGNANCY — Management of a woman with lactotroph adenoma who wants to conceive should begin with advice about the potential risks of pregnancy to her and the fetus. The main concern for the mother is adenoma growth, while the potential risk for the fetus is exposure to dopamine agonists, which are used to permit ovulation. To date, neither bromocriptine nor cabergoline, the dopamine agonists used for this purpose, have been associated with adverse fetal outcomes when compared with what is expected in the general population. (See 'Restoration of ovulation' below.)

Discuss risk of adenoma growth — The principal risk during pregnancy to a mother with a lactotroph adenoma is an increase in adenoma size sufficient to cause neurologic symptoms, most importantly visual impairment. The theoretical basis for an increase in size is that the increased serum level of estradiol during pregnancy causes lactotroph hyperplasia. As an example of the effect of the increased level of estradiol in normal pregnancy, a study of 20 normal nonpregnant women and 32 normal pregnant women showed a greater increase in pituitary size, as assessed by magnetic resonance imaging (MRI), the later in pregnancy, so that the volume during the third trimester was more than double that in nonpregnant women (figure 1) [1]. Similarly, in women with lactotroph adenomas who become pregnant, the higher levels of estradiol of pregnancy may increase the size of the lactotroph adenoma.

The risk that the increase in size of a lactotroph adenoma will be clinically important depends upon the size of the adenoma before pregnancy.

Microadenoma — For a microadenoma (<10 mm in diameter), the risk of growth is very low [2-5]. A review of 14 studies reporting a total of 764 patients with lactotroph microadenomas showed that only 2.4 percent exhibited a symptomatic increase in the size of the adenoma during pregnancy [6].

Macroadenoma — The risk of growth of a lactotroph macroadenoma (≥10 mm) during pregnancy is substantially higher. In the same review as above [6], only 4.8 percent of 148 women who had macroadenomas that had been treated by prior surgery or radiation developed clinically significant enlargement during pregnancy, but 22.9 percent of 214 women who had not had such treatment did. Enlargement not accompanied by symptoms or visual field deficit was not counted.

TREATMENT BEFORE PREGNANCY: MICROADENOMAS

Restoration of ovulation — Hyperprolactinemia suppresses pituitary gonadotropin secretion, resulting in irregular menstrual cycles and anovulatory infertility. Serum prolactin concentrations between 50 to 100 ng/mL (normal <15 to 20 ng/mL), typically cause either amenorrhea or oligomenorrhea, while levels greater than 100 ng/mL result in deficient estradiol and progesterone secretion and amenorrhea. (See "Clinical manifestations and evaluation of hyperprolactinemia", section on 'Menstrual cycle dysfunction'.)

For women with lactotroph microadenomas, treatment with a dopamine agonist usually normalizes prolactin and thereby removes the inhibition of gonadotropin secretion and restores normal ovulation and fertility.

Dopamine agonist therapy — A dopamine agonist is the treatment of choice for women with a lactotroph adenoma. A marked reduction in the serum prolactin concentration often occurs within two to three weeks (figure 2). (See "Management of hyperprolactinemia", section on 'Overview of dopamine agonists'.)

Dosing is as follows:

●For cabergoline, start at 0.25 mg twice a week. If the serum prolactin concentration is not normal after one to two months, the dose can be increased to 0.5 mg twice a week or, if necessary, 1 mg twice a week. Sometimes, even higher doses are needed [7].

●For bromocriptine, start with 1.25 mg at bedtime for one week, then 1.25 mg twice a day for one to two months. If the serum prolactin concentration does not fall to near normal or normal by then, the dose can be increased to 2.5 mg twice a day and, if necessary, to 5 mg twice a day. If nausea occurs or if serum prolactin does not decrease to normal, consider changing to cabergoline.

The occurrence of regular menstrual cycles during treatment indicates that the woman is probably ovulating. Following correction of hyperprolactinemia, approximately 80 percent of women will ovulate, and pregnancy rates of 70 to 80 percent can be achieved [8]. Neither cabergoline nor bromocriptine has been associated with an increased risk of miscarriage, congenital malformations, or pregnancy complications such as preterm deliveries.

We suggest stopping the dopamine agonist in women with either a micro- or macroadenoma once pregnancy has been confirmed because the safety of continued usage has not been established.

For women who do not ovulate or do not conceive with dopamine agonist therapy, clomiphene citrate may be added [9]. If unsuccessful, gonadotropin therapy may be needed, although this therapy is associated with high serum estradiol concentrations during treatment and a significant risk of multiple gestations. (See "Ovulation induction with clomiphene citrate" and "Overview of ovulation induction", section on 'Gonadotropin therapy'.)

Risks to fetus — Although dopamine agonists are typically discontinued when pregnancy is confirmed, pregnancy has usually progressed at least two weeks before confirmation occurs and the drug discontinued, so the fetus is exposed to the dopamine agonist during that time. Evidence to date does not suggest risk to the fetus from this exposure.

Data from over 6000 pregnancies suggest that the administration of bromocriptine during the first month of pregnancy does not harm the fetus [5]. In this series, the incidence of spontaneous abortions (9.9 percent), multiple births (1.7 percent), and malformations (1.8 percent) was no higher than in the general population. In addition, in a study of children followed for up to nine years after exposure to bromocriptine in utero, no harmful effects were noted [10].

Rarely, dopamine agonist treatment is resumed during pregnancy if adenoma size increases so much as to impair vision (see 'Treatment of enlarging adenoma' below). Continuous use of bromocriptine during pregnancy has been reported in approximately 100 women. Although the rate of congenital malformations did not appear to be higher than nonexposed pregnancies, there was one case of undescended testis and one of talipes deformity [5,11].

Although the number of pregnancies in women taking cabergoline at the time of conception is much smaller (968), the evidence suggests that this drug is safe as well. In one review of over 700 cases, the incidence of spontaneous abortions (7.5 percent), multiple births (2.4 percent), and malformations (2.4 percent) was no higher than in the general population [6]. Patients with Parkinson disease treated with high doses of cabergoline (eg, >20 mg per week) have an increased risk of valvular heart disease, but this risk has not been demonstrated using the lower doses used for lactotroph adenomas [12]. (See "Valvular heart disease induced by drugs", section on 'Hyperprolactinemia'.)

Choice of drug — When a dopamine agonist is needed to lower the serum prolactin concentration to permit ovulation, cabergoline has the advantage that it is more likely to be tolerated and more likely to be effective in lowering the prolactin, although bromocriptine has the advantage of the greater certainty that it does not cause birth defects. We typically let women choose which dopamine agonist they would like to try. Women who are more concerned about nausea from bromocriptine often choose cabergoline, but women who are especially concerned about the possibility of birth defects may choose bromocriptine. (See "Management of hyperprolactinemia", section on 'Overview of dopamine agonists'.)

TREATMENT BEFORE PREGNANCY: MACROADENOMAS — For a woman with macroadenoma, adenoma size should be reduced and ovulation should be restored before pregnancy is attempted. A dopamine agonist may do both, but surgery may also be required.

Dopamine agonist to decrease size — A woman who has a lactotroph macroadenoma should be advised of the relatively higher risk of clinically important adenoma enlargement during pregnancy, as described above [5] (see 'Discuss risk of adenoma growth' above). We recommend a dopamine agonist as the initial treatment of a lactotroph adenoma, whether or not the adenoma is elevating the optic chiasm. Once the adenoma size has decreased dramatically and is well within the confines of the sella and ovulation has been restored, pregnancy can be attempted. Reduction in size in this way should reduce the chance of clinically important enlargement during pregnancy [2,13]. The dopamine agonist should be discontinued when pregnancy has been confirmed.

Transsphenoidal surgery to decrease adenoma size — If the adenoma elevates the optic chiasm and does not shrink substantially in response to a dopamine agonist, we recommend transsphenoidal surgery to reduce adenoma size. Prior surgery reduces the chance that symptomatic expansion will occur during pregnancy [6], but it may still occur. (See "Radiation therapy of pituitary adenomas", section on 'Lactotroph adenomas (prolactin-secreting adenomas)'.)

We also recommend surgery in a woman whose macroadenoma (≥10 mm) is unresponsive to bromocriptine or cabergoline, even if it is not elevating the optic chiasm, because medical treatment would not likely be effective if the adenoma enlarges during pregnancy.

DURING PREGNANCY — Women with lactotroph adenomas, in particular those with macroadenomas, should be monitored closely during pregnancy. The approach outlined here is consistent with the 2011 Endocrine Society Clinical Practice Guidelines on the diagnosis and treatment of hyperprolactinemia [14].

Monitoring — Patients should be seen at routine intervals and asked about headaches and changes in vision (as indicators of potential adenoma growth).

●Women with microadenomas should be seen every three months.

●Women with macroadenomas should also be seen at least every three months, and more often the larger the adenoma.

Serum prolactin — During normal pregnancy, serum prolactin concentrations increase to as high as 400 ng/mL. Women with lactotroph adenomas may experience an increase in serum prolactin to pretreatment levels (figure 3). However, not all women with lactotroph adenomas experience a similar increase [5].

The Endocrine Society guidelines recommend against measuring prolactin during pregnancy, because it can be difficult to distinguish the normal pregnancy-associated rise in prolactin from that associated with adenoma growth [14]. However, we do measure prolactin in women with both macro- and microadenomas every three months during pregnancy because we find it reassuring if the prolactin does not increase above 400 ng/mL. If the prolactin does increase to >400 ng/mL, we obtain visual field testing.

Visual field testing — For most pregnant women with lactotroph adenomas, routine visual field testing is not indicated. However, women who develop visual symptoms during pregnancy should have visual field testing. In addition, women whose macroadenomas extend above the sella should undergo visual field testing before pregnancy and every three months during the pregnancy, even if the patient has no visual symptoms. If a visual field defect consistent with a sellar mass is found (diminished vision in the temporal fields [bitemporal hemianopsia]), magnetic resonance imaging (MRI) without contrast should be performed.

Pituitary MRI — Routine pituitary magnetic resonance imaging (MRI) is not indicated in women with lactotroph adenomas during pregnancy, because the risk of adenoma growth is very low. However, if a patient develops severe headaches or visual field abnormalities, pituitary MRI without contrast should be performed to assess adenoma size. (See 'Discuss risk of adenoma growth' above.)

Treatment of enlarging adenoma — If the adenoma has enlarged to a degree that could account for the headaches and/or visual field defect, the woman should be treated with cabergoline or bromocriptine throughout the remainder of the pregnancy, and she should be seen at least once a month to reevaluate symptoms and visual fields. This treatment will usually decrease the size of the adenoma and alleviate the symptoms [11,15].

We suggest using the same dopamine agonist the patient took and tolerated previously. (See 'Choice of drug' above.)

If bromocriptine is used first and the adenoma does not respond, cabergoline should then be tried because it is more effective for decreasing adenoma size [16]. If cabergoline is not successful in alleviating severely compromised vision after several weeks, we suggest transsphenoidal surgery in the second trimester. In contrast, in the third trimester, surgery for persistent visual symptoms should be deferred until after delivery, if possible.

Pituitary apoplexy — Pituitary apoplexy refers to sudden hemorrhage into the pituitary, a rare event with potential serious neurologic and endocrine consequences. Apoplexy can occur in patients with pituitary micro- or macroadenomas, including women with lactotroph macroadenomas during pregnancy. In its most dramatic presentation, apoplexy causes the sudden onset of excruciating headache, diplopia due to pressure on the oculomotor nerves, and hypopituitarism. All pituitary hormonal deficiencies can occur, but the sudden onset of corticotropin (ACTH) and therefore cortisol deficiency is the most serious because it can cause life-threatening hypotension. It should be treated with high-dose hydrocortisone. (See "Causes of hypopituitarism", section on 'Pituitary apoplexy'.)

Most patients who develop apoplexy were not known to have an adenoma previously, and when tissue is excised surgically, it is necrotic, so the cell type cannot be identified.

AFTER PREGNANCY

Breastfeeding and dopamine agonists — Breastfeeding increases serum prolactin concentrations (figure 4) but does not appear to increase the risk of lactotroph adenoma growth [17,18]. Therefore, breastfeeding is an option for women with micro- and macroadenomas that remained stable in size during pregnancy. Dopamine agonist therapy, which lowers serum prolactin and inhibits lactation, should be withheld until breastfeeding is completed.

In contrast, breastfeeding is contraindicated in women who have visual field impairment because they should be treated with a dopamine agonist.

Normalization of prolactin after pregnancy — To evaluate the need for further dopamine agonist therapy after pregnancy, serum prolactin should be measured approximately three months after delivery in women who do not breastfeed and after cessation of breastfeeding in those who do. Serum prolactin normalizes within 6 to 12 weeks postpartum in women who do not breastfeed. (See "Causes of hyperprolactinemia", section on 'Nipple stimulation and breast examinations'.)

●In a study of 143 pregnancies in 91 patients with hyperprolactinemia treated with cabergoline prior to pregnancy, no further treatment was necessary to maintain a normal serum prolactin concentration in 68 percent of the patients for up to 60 months postpartum [19]. Breastfeeding did not affect the results. Recurrence was slightly greater in those who had macroadenomas than in those who had microadenomas.

●In a study of 104 pregnancies in 73 patients with lactotroph adenomas treated with a dopamine agonist prior to pregnancy, 41 percent had a normal serum prolactin concentration a median of 22 months after delivery or cessation of lactation [20].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Hyperprolactinemia/prolactinoma".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they 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. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Prolactinoma (The Basics)")

●Beyond the Basics topics (see "Patient education: High prolactin levels and prolactinomas (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Management of a woman with a lactotroph adenoma should begin before conception with advice to her and her partner about the potential risks to her and the fetus. The main concern for the mother is adenoma growth, while the main concern for the fetus is exposure to a dopamine agonist. (See 'Overview' above.)

●When a dopamine agonist is needed to lower the serum prolactin concentration to permit ovulation, we suggest a dopamine agonist (either cabergoline or bromocriptine) (Grade 2C). (See 'Restoration of ovulation' above.)

Cabergoline has the advantage that it is more likely to be tolerated and more likely to be effective in lowering the prolactin, but bromocriptine has the advantage of the greater certainty that it does not cause birth defects. (See 'Dopamine agonist therapy' above.)

●We suggest stopping dopamine agonist therapy (for women with either a microadenoma or macroadenoma) once pregnancy has been confirmed because the safety of continued usage throughout pregnancy has not been established (Grade 2C). (See 'Dopamine agonist therapy' above.)

●For women with macroadenomas, we suggest treatment with a dopamine agonist to decrease the size of the adenoma prior to pregnancy, whether the adenoma elevates the optic chiasm or not (Grade 2C). (See 'Dopamine agonist to decrease size' above.)

●We suggest transsphenoidal surgery prior to pregnancy when the macroadenoma does not decrease to well within the sella in response to a dopamine agonist (Grade 2C). We also suggest transsphenoidal surgery when a macroadenoma is within the sella but does not respond at all to a dopamine agonist because if it enlarges during pregnancy, use of a dopamine agonist will not decrease the size. (See 'Transsphenoidal surgery to decrease adenoma size' above.)

●During pregnancy, women with either a micro- or macroadenoma should be seen every three months to evaluate for possible adenoma growth. (See 'Monitoring' above.)

●For women with evidence of macroadenoma growth on pituitary magnetic resonance imaging (MRI; performed for severe headaches or visual field abnormalities), we suggest treatment with cabergoline or bromocriptine throughout the remainder of the pregnancy (Grade 2C). Transsphenoidal surgery is sometimes needed if dopamine agonists are not successful and vision is severely compromised. (See 'Treatment of enlarging adenoma' above.)

●Breastfeeding is not contraindicated in women who have lactotroph adenomas, but dopamine agonists should not be used during breastfeeding, because they impair lactation. An exception is a woman who has visual field impairment, who should not breastfeed and should be treated with a dopamine agonist. (See 'Breastfeeding and dopamine agonists' above.)

●Forty to 60 percent of women who were treated with dopamine agonists for lactotroph adenomas prior to pregnancy do not require them afterwards. Therefore, women should be reevaluated by measurement of the serum prolactin concentration three months after delivery in women who do not breastfeed or after cessation of breastfeeding. (See 'Normalization of prolactin after pregnancy' above.)