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Cabergoline and pregnancy
clinically significant tumor enlargement

Cabergoline and pregnancy

Prolactinomas are the most frequent functional benign pituitary tumors due to a small or large pituitary micro- or macroadenoma. Infertility and gonadal dysfunction are the most common symptoms. Prolactin level normalization, tumor reduction, ovulation, and fertility restoration can be achieved with dopamine agonists (DA) (bromocriptine or Cabergoline). Cabergoline is usually preferred over bromocriptine because of its greater effectiveness and tolerability. Because of their higher efficacy and tolerability, Cabergoline is often preferred over bromocriptine during pregnancy management. The pituitary gland undergoes global hyperplasia throughout pregnancy as a result of an increased serum estrogen level, which might lead to growth in volume and potential mass effect with visual loss. Microadenomas have a 3 percent chance of growing, while macroadenomas that had not previously been operated on have a 32 percent chance. Both drugs are considered to be safe during pregnancy, with bromocriptine being considerably more likely to cross the placenta than Cabergoline, with no link between higher risk of pregnancy loss or preterm birth. It is recommended that DAs be discontinued as soon as pregnancy is confirmed unless the patient has invasive macroprolactinomas or pressure symptoms. During pregnancy, prolactinoma can be treated in a variety of ways, including through DA therapy.

Introduction

Prolactinomas are adenomas that develop in the pituitary gland and produce prolactin which is responsible for milk production. Prolactin secretion and release are controlled by tonic dopamine inhibition from the hypothalamus. The breast is prolactin’s major target site, but it has been discovered in various tissues including the liver, ovary, testis, and prostate. Prolactin has two major functions: the stimulation and maintenance of lactation, as well as acting as a growth factor, neurotransmitter, or immunoregulator through autocrine or paracrine mechanisms.

Prolactinomas are a type of pituitary gland tumor that occurs when the body makes too much prolactin. Prolactinomas are typically macroadenomas (≥10 mm) and result from excessive prolactin production by the pituitary gland. Prolactinomas occur at a frequency of 60 to 100 cases per million people. It is particularly prevalent in females, especially during puberty. The incidence rate was 23.9 per 100,000 person-years among women between the ages of 25 and 34 years old. Prolactinomas are usually microadenomas (less than 10 mm) that produce high levels of prolactin, resulting in amenorrhea, galactorrhea, and infertility in women. Prolactinomas are a very rare type of pituitary tumor. They are generally benign, although they can occasionally cause infertility in men and women. Mass effects, such as headache and vision loss, as well as hypogonadism and impotence, are typical symptoms in males with prolactinomas. In both men and women, hyperprolactinemia may lead to bone loss over time.

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Dopamine agonists (DAs) have been increasingly used as a treatment of choice for prolactinomas because they reduce prolactin levels and cause tumor shrinkage. Currently, surgery is only utilized in the event of radiotherapy failure or resistance to DAs.

The pituitary gland undergoes global hyperplasia during pregnancy as a result of a progressive increase in serum estrogen levels, which may lead to tumor growth with potential mass effect and vision loss.

Prolactinoma during pregnancy

pregnancy tumor cells

Prolactinomas are tumor cells that contain estrogen receptors. During pregnancy, there is an increase in the volume of the prolactinoma owing to lactotroph cell hyperplasia, which results in a substantial boost in serum prolactin and a progressive rise in serum prolactin levels. The major worry is that the tumor may grow during pregnancy. The chance of tumor growth during pregnancy is linked to tumor size. According to research, while macroprolactinomas grow by 3%, macroprolactinomas increase by 32% if they had not previously been treated.

Before getting pregnant, magnetic resonance imaging (MRI) should be performed to document tumor size and serve as a basis for comparison with MRIs done during pregnancy. Furthermore, MRI is useful in determining whether bleeding into a tumor or simple tumor growth is occurring throughout pregnancy.

Prolactinomas are more difficult to treat during pregnancy, and although medical treatment is effective, not enough safety data are available to advocate its use routinely throughout pregnancy. The endocrine society’s clinical practice guidelines for the management and treatment of prolactinomas recommend that DAs be discontinued as soon as possible after confirmation of pregnancy, with the exception of women with invasive macroprolactinomas.

Bromocriptine is a dopamine D2 receptor agonist that has agonistic and antagonistic effects on D1 receptors and is an ergoline derivative. Because of its short half-life, it is necessary to administer m u multiple dosings throughout the day. The rate of spontaneous abortions, ectopic pregnancies, and congenital abnormalities in women taking bromocriptine throughout early pregnancy are no higher than that in the general population. In a study of 2,587 pregnant women, out of which 2,437 were at risk for spontaneous abortion, fetal malformations, or multiple deliveries that did not affect postnatal development. The risk of spontaneous abortions in a study of 6,329 women treated with bromocriptine early in pregnancy was 9.9%, which was not greater than that seen in the general population (10.9%). Furthermore, the long-term follow-up to 9 years of children born from mothers taking bromocriptine did not result in any negative effects on child physical development or psychomotor development abnormalities was reported at 5.5 years (1–20 years) after birth.

Furthermore, bromocriptine use throughout pregnancy resulted in the best results is around 100 cases.

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Cabergoline is a D2 DA with higher affinity and selectivity for dopamine receptors than ergolines. It has a long duration of action, allowing once- or twice-weekly administration with improved tolerability and patient compliance. Furthermore, Cabergoline had a pregnancy rate greater in infertile women with prolactinoma than bromocriptine.

A handful of studies have also suggested that Cabergoline is safe to use throughout pregnancy. The same outcomes have been reported in women who were on Cabergoline previously and during pregnancy. Over 800 such pregnancies have been documented, with around 350 being exposed during the first weeks of pregnancy, according to one research (of which roughly 250 ended in spontaneous abortion), with no significant difference in the rate of spontaneous abortion, premature delivery, multiple offspring, or neonatal malformations.

pregnancy tumor cells

In a a retrospective analysis of 103 pregnancies in 90 women with hyperprolactinemia and the follow-up of the 61 children, no significant abnormalities were linked to Cabergoline dosages or time of exposure. The data from 12 years post-exposure in the kids born to moms treated with DA revealed no influence on their psychomotor development or physical problems. According to previous research, there was no significant increase in miscarriage or malformation risk associated with DA usage.

Quinagolide is a non-ergot DA medication with a selective dopamine-2 receptor agonist and prolactin lowering impact. It’s is generally taken once daily, and it has better tolerability and an easy dosing regimen than Bromocriptine. It has less risk of side effects than Bromocriptine. Spontaneous abortion occurred in 14 percent of mothers treated with Quinagolide in an analysis of 176 pregnancies (average 37 days) conducted over 10 years; one baby was delivered prematurely, while another was ectopic gestation. In a small study of nine pregnancies, two women were given two Quinagolide and had no complications.

There have been over 200 Quinagolide-induced pregnancies in women, and there were no apparent negative effects on pregnancy or fetal development.

As a result, each woman with prolactinomas should be informed about the natural history of prolactinomas and advised to talk with her doctor regarding plans for pregnancy before being evaluated.

significant asymptomatic tumor growth

The determination of the best treatment option is a personal decision based on the size of the tumor. Prolactinomas during pregnancy have been extensively discussed, with varied outcomes. A recent study revealed a prolactin normalization rate of more than 40% without medical intervention for a median time follow-up of 22 months after delivery and cessation of lactation.

Impact of pregnancy and breastfeeding on prolactin levels, tumor volume, and remission rate

symptomatic tumor growth

Two-thirds of women with hyperprolactinemia have the condition go away after DA withdrawal, according to current research. In one study, pregnancy was found to cure non-tumoral hyperprolactinemia (NTHP) in 76 percent of patients, 70% of macroprolactinomas, and 64% of macroprolactinomas, with a a higher relapse rate among patients with macrophrinocarcinomas and those with microphrinocarcinomas who had a a visible tumor on MRI at treatment termination.

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In recent research, 100% of patients with NTHP and 66% of those with macroprolactinomas experienced complete remission, as did 70% of patients with macroprolactinomas. The underlying mechanisms are unknown, but they are usually attributed to the self-infarction. of the tumor.

Any reduction in prolactin levels induced by breastfeeding has not been shown to raise the risk of tumor growth, according to clinical research. Women may thus breastfeed normally and resume DA after weaning.

Conclusion

Prolactinoma is a difficult disease to treat during pregnancy. Clinical research examining the benefits of medical therapy versus other treatments are rare, therefore each patient is treated on an individual basis. Microadenoma has a good prognosis, allowing patients to safely stop DAs with close clinical monitoring; nevertheless, macroadenoma must be managed before conception since tumor development is quite probable.

Frequently Asked Questions

Can you get pregnant while taking a Cabergoline?

Cabergoline is a pregnancy category B drug, which means that it has not been shown to cause harm to the unborn baby in animal studies. However, because of the potential risks associated with any medication taken during pregnancy, talk to your doctor before taking a cabergoline if you are pregnant or planning to become pregnant.

Can you breastfeed while taking Cabergoline?

There is no known risk to breastfeeding while taking cabergoline. Talk to your doctor if you have any questions about whether it is safe for you to take a cabergoline and breastfeed.

What is the impact of pregnancy on prolactinoma?

Pregnancy may cause a reduction in prolactin levels and can sometimes lead to tumor shrinkage. Prolactin levels decrease gradually during the first trimester and increase by 50% in the third trimester.

How does breastfeeding affect prolactinoma?

Prolactin levels are significantly lower in women who are breastfeeding than those who are not. The natural reduction of prolactin after birth may have a beneficial effect on tumor growth, even if it reduces fertility. In addition, most studies show that high doses of bromocriptine do not cause any side effects to infants when taken by nursing mothers. However, some research has shown that low-dose bromocriptine may be associated with decreased milk production, which is why cabergoline should be used instead of bromocriptine lactating mothers.

Is Cabergoline a fertility drug?

Cabergoline is an FDA-approved drug to treat hyperprolactinemia, a condition characterized by high prolactin levels. Thus, it can be used as a fertility medication in women who have not had children and wish to conceive. If you are interested in using cabergoline for fertility treatment or if you have already taken this medication and become pregnant, talk to your doctor about the potential risks and benefits.

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Malik

Malik

Gynecologist, Reproductologist
Specialist in Actual Problems of Gynecological Endocrinology

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