What is the workup for a 23-year-old woman with hyperprolactinemia (elevated prolactin), normal estradiol, Follicle-Stimulating Hormone (FSH), thyroid function, and Luteinizing Hormone (LH) levels, presenting with irregular menstrual periods?

From the Guidelines

For a 23-year-old woman with hyperprolactinemia and irregular menstrual periods, I strongly recommend a comprehensive workup starting with a repeat prolactin measurement, preferably in the morning after fasting and avoiding breast stimulation, as a single prolactin measurement taken at any time of the day is sufficient to assess hyperprolactinaemia 1. The next step should be to investigate the cause of hyperprolactinemia, considering that prolactin secretion also rises in response to stress, and sampling can be repeated on a different day with two or three samples at 20–60 min intervals, using an indwelling cannula, to differentiate stress-related hyperprolactinaemia from organic disease 1. Key considerations in the workup include:

• Pituitary MRI with contrast to evaluate for prolactinoma, which is the most common cause of pathologic hyperprolactinemia in young women
• Medication review, as many drugs can elevate prolactin, including antipsychotics, certain antidepressants, metoclopramide, and some antihypertensives 1
• Pregnancy test, renal and liver function tests, and assessment for polycystic ovary syndrome
• Assessment for macroprolactin levels where serum prolactin is found to be mildly or incidentally elevated, as macroprolactinaemia can be present in 10–40% of individuals with hyperprolactinaemia 1 If no obvious cause is found and prolactin remains elevated, a trial of cabergoline (starting at 0.25mg twice weekly) may be appropriate both as treatment and to help confirm diagnosis, as prolactinomas typically respond well to dopamine agonists 1. It is essential to note that hyperprolactinemia can cause irregular periods by interfering with GnRH pulsatility, leading to reduced FSH/LH secretion and subsequent anovulation, even when gonadotropin levels appear normal on single measurements 1. The diagnosis of hyperprolactinaemia requires age-specific and sex-specific prolactin reference ranges and the exclusion of confounding conditions such as hypothyroidism, renal and/or hepatic impairment, and use of medications that cause hyperprolactinaemia 1.

From the Research

Diagnostic Evaluation

The diagnostic evaluation for a 23-year-old woman with hyperprolactinemia, normal estradiol, Follicle-Stimulating Hormone (FSH), thyroid function, and Luteinizing Hormone (LH) levels, presenting with irregular menstrual periods, involves several steps:

• Exclusion of other causes of hyperprolactinemia, such as pregnancy, primary hypothyroidism, numerous medications, and miscellaneous causes 2
• Performance of a head scan, preferably an MRI, to exclude a "pseudoprolactinoma" which would require surgery 2
• Measurement of prolactin levels, with levels of 100 to 200 micrograms/L commonly considered diagnostic for the presence of a prolactinoma, although prolactinoma cannot be excluded in the presence of lower levels 3

Treatment Options

The treatment of choice for nearly all patients with hyperprolactinemic disorders is medical, with dopamine agonists (bromocriptine, pergolide, cabergoline) being extremely effective in lowering serum prolactin, restoring gonadal function, decreasing tumor size, and improving visual fields 2, 4

• Bromocriptine is usually given once or twice daily, while cabergoline has a long duration of action and is given once or twice weekly 4
• Cabergoline is clearly superior to bromocriptine in efficacy (PRL suppression, restoration of gonadal function) and tolerability 4
• For the infrequent patient unable to tolerate, or resistant to, medical therapy, neurosurgical transsphenoidal resection may be necessary, particularly if the patient has a large lesion jeopardizing the optic chiasm 2

Management of Hyperprolactinemia

Hyperprolactinemia can be treated very effectively with bromocriptine, and this drug appears to have become the favorite form of treatment 5

• In the case of obvious tumors, hypophysectomy is indicated 5
• When there are smaller tumors, irradiation of the pituitary gland previous to bromocriptine treatment may prevent expansion of the gland during subsequent pregnancy 5
• The mainstay of treatment of hyperprolactinemia is to improve bothersome galactorrhea or hypogonadism by using dopamine agonists and/or replacement of sex hormone(s) 6