15 Mar Hyperprolactinemia & Infertility
Prolactin is a hormone secreted by the pituitary gland and its function is to enhance breast development and initiate lactation. Prolactin levels get normally elevated in pregnancy and during nursing. Prolactin-secreting adenomas (prolactinomas) are the most common functioning pituitary tumor. Most of these prolactinomas are microadenomas (<10 mm). In women, hypersecretion of prolactin leads to amenorrhea, galactorrhea, and infertility. In men, hyperprolactinemia leads to hypogonadism and infertility; the latter fertility resulting from suppression of gonadotropin secretion.
Hyperprolactinemia affects the fertility potential by impairing pulsatile secretion of GnRH. IN women, this interferes with the action of gonadotropins at the ovarian level, which then interferes with ovulation. Hyperprolactinemia also causes galactorrhea in addition to menstrual and ovulatory issues. If there is a patient with unexplained infertility, menstrual irregularity with or without hirsutism, galactorrhea with or without amenorrhea, then their serum prolactin levels should be tested. Mild hyperprolactinemia can cause infertility even if there is regular menstruation. Although, other hormonal reason for galactorrhea and hyperprolactinemia can be hypothyroidism. This is because hypothyroidism causes an increased secretion of TRH which stimulates thyrotrophs and lactotrophs, causing an increase in the levels of both TSH & prolactin.
Elevated prolactin levels are thought to inhibit the secretion of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In addition, prolactin may act directly on GnRH neurons to suppress GnRH secretion.
There are two main reasons why patients with hyperprolactinemia need to be treated: existing or new neurologic symptoms (because of impingement of the adenoma on the surrounding structures), and hypogonadism or other complications such as infertility. Women with mild hyperprolactinemia and normal cycles who are trying to conceive should also be treated.
Of all the pituitary adenomas, prolactinomas are one of the most amenable ones to pharmacologic treatment. This is because of the availability of dopamine agonists, which usually decrease both the secretion and size of these tumors. The treatment is based on normalizing prolactin, reducing tumor size, reversing hypogonadism, and restoring fertility. The most commonly used agents for that purpose are dopamine receptor agonists, bromocriptine and cabergoline. Bromocriptine inhibits prolactin activity and decreases tumor size in 80%–90% of patients with microadenomas, but its side effects include nausea, orthostatic hypotension, headache, and fatigue. Cabergoline is a more selective D2 receptor agonist, and that makes it more effective and with fewer side effects. About 10-20% of the patients show intolerance toward dopamine antagonists leading to discontinuation. Hyperprolactinemia due to nonadenoma causes should also be treated with these medications if there is evidence of hypogonadism.
Prolactinomas that are 1 cm or more in size are called a macroadenoma. These are the ones that typically cause neurologic symptoms, such as visual impairment or headache. Treatment for them tends to be surgical.
These patients need to be properly assessed for hyperprolactinemia and further testing (lab testing and sometimes imaging is needed to choose appropriate treatment and further steps of management.