Prolactin is a hormone produced by the pituitary gland. Its primary function is to stimulate milk production after childbirth, but it also plays a significant role in regulating the reproductive system. When prolactin levels in the blood are abnormally high, a condition known as hyperprolactinemia occurs. This hormonal imbalance interferes with normal ovulation, making conception difficult for many women. While high prolactin presents a barrier to getting pregnant, successful pregnancy is possible with medical intervention to restore hormonal balance.
The Role of Prolactin in the Menstrual Cycle
Elevated prolactin disrupts the delicate communication network known as the hypothalamic-pituitary-gonadal (HPG) axis, which governs the menstrual cycle. High levels of prolactin suppress the pulsatile release of Gonadotropin-releasing hormone (GnRH) from the hypothalamus. This suppression creates a cascade effect, signaling the pituitary gland to reduce its output of Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH).
The reduced levels of FSH and LH prevent the ovarian follicles from developing properly. Crucially, the lack of an LH surge inhibits the release of a mature egg from the ovary, resulting in anovulation. Without a released egg, pregnancy cannot occur.
In some cases, ovulation may still happen, but hyperprolactinemia can negatively affect the function of the corpus luteum, the temporary structure that produces progesterone after the egg is released. Progesterone is necessary to prepare the uterine lining for implantation and sustain an early pregnancy. High prolactin can lead to a luteal phase defect, characterized by reduced progesterone secretion, which can also impair fertility.
Common Causes of Hyperprolactinemia
The causes of hyperprolactinemia include pathological, pharmacological, and physiological reasons. One of the most common pathological causes is a prolactinoma, a non-cancerous tumor of the pituitary gland that secretes excess prolactin. These tumors are classified by size: microadenomas are smaller than 10 millimeters, while macroadenomas are larger.
A significant portion of hyperprolactinemia cases are drug-induced, caused by medications that interfere with the brain’s dopamine pathways. Dopamine naturally inhibits prolactin secretion, so medications that block its action—such as certain antipsychotics, some antidepressants, and specific blood pressure drugs like verapamil—can lead to elevated prolactin levels. Stopping or changing the medication, under medical supervision, often resolves this type of hyperprolactinemia.
Primary hypothyroidism can also lead to high prolactin. Low thyroid hormone levels cause the hypothalamus to increase its release of Thyrotropin-releasing hormone (TRH) to stimulate the pituitary gland. TRH also acts as a prolactin-releasing factor, causing a secondary elevation in prolactin.
Other less frequent causes include chronic kidney disease, liver failure, and significant physical or emotional stress.
Diagnostic Testing and Thresholds
Diagnosis of hyperprolactinemia begins with a blood test to measure the prolactin level, ideally collected in the early morning in a fasting state. Prolactin levels fluctuate and can be temporarily raised by stress or a recent meal. For women who are not pregnant or nursing, the upper limit of the normal range is below \(25 \text{ ng/mL}\) in most laboratories, and levels consistently above this threshold are considered elevated.
A significantly high prolactin level, particularly one exceeding \(100 \text{ ng/mL}\) or \(200 \text{ ng/mL}\), strongly suggests a prolactinoma. However, a common diagnostic challenge is macroprolactinemia. This condition involves macroprolactin, a large, biologically inactive complex of prolactin bound to an antibody.
Since standard lab assays detect this large complex, the reading can be falsely high, even if the patient has normal levels of active prolactin and no symptoms of infertility. To rule this out, a Polyethylene Glycol (PEG) precipitation test is performed to measure only the small, active form of the hormone. If a true elevation is confirmed, further investigation is necessary, typically involving an MRI of the pituitary gland and a blood test for Thyroid-Stimulating Hormone (TSH) for underlying hypothyroidism.
Medical Strategies for Achieving Pregnancy
The primary goal of treating hyperprolactinemia in women seeking pregnancy is to lower prolactin levels to the normal range and restore regular, ovulatory menstrual cycles. This is achieved through the use of Dopamine Agonists (DAs), medications that mimic the action of dopamine. They work by binding to D2 receptors on the pituitary cells that produce prolactin, inhibiting its release and often shrinking the size of a prolactinoma.
Cabergoline and Bromocriptine are the two most commonly prescribed dopamine agonists. Cabergoline is preferred due to its higher efficacy in normalizing prolactin levels and its superior tolerability profile. These medications are effective, restoring ovulation and fertility in over 90% of women with hyperprolactinemia-related infertility.
For women with a microadenoma, the treatment plan typically involves stopping the dopamine agonist once pregnancy is confirmed. The risk of the small tumor growing large enough to cause symptoms during pregnancy is very low, estimated at two to three percent. Both Cabergoline and Bromocriptine have safety data demonstrating no increased risk of miscarriage or congenital malformations when exposure is limited to the period leading up to conception and the very early weeks of pregnancy.
Management is more cautious for women with a macroadenoma, as the risk of symptomatic tumor enlargement during pregnancy is higher, potentially reaching 20 to 32 percent if the tumor was not previously treated. In these cases, the dopamine agonist may be continued throughout the pregnancy to control tumor growth, or the patient will be closely monitored with regular visual field testing. Bromocriptine has traditionally been the preferred agent for use throughout pregnancy due to its larger historical safety database, though Cabergoline is increasingly recognized as a safe and effective option when continued use is needed.