Hyperprolactinemia and Polycystic Ovary Syndrome

Peter Kovacs, MD, PhD


April 10, 2003


It has been described by some authors that women with polycystic ovary syndrome (PCOS) may have elevated levels of prolactin. However, a diagnostic criterion is to rule out other possible causes, including hyperprolactinemia. For research purposes, and in a given patient, how can we establish that hyperprolactinemia is a part of the syndrome or that it excludes a diagnosis of PCOS?

Carlos Andres Valverde, MD

Response from Peter Kovacs, MD, PhD

PCOS occurs in up to 10% of reproductive-age women. It is the most common etiology underlying ovulatory problems. Several diagnostic criteria are used, but the most widely accepted definition of the syndrome is chronic anovulation or oligoovulation and clinical or laboratory hyperandrogenemia in the absence of other sources of androgen excess. Hyperprolactinemia is a less common cause for menstrual irregularities; its incidence has been reported to be between 0.4% and 17%. Higher prevalence has been reported among women with PCOS. As elevated androgen levels can occur with hyperprolactinemia, it has to be ruled out in order to establish the diagnosis of PCOS.

Prolactin is the only anterior pituitary hormone that is under constant suppression. Dopamine, produced in the hypothalamus, reaches the anterior pituitary via the pituitary portal circulation and suppresses prolactin release. Hyperprolactinemia results when this suppression is inhibited. Prolactin secretion has a circadian rhythm, and it changes throughout the menstrual cycle; therefore, it should be measured on at least 2 occasions. Pregnancy, nipple stimulation, lactation, stress, eating, thyroid abnormalities, and certain drugs can all result in hyperprolactinemia, so they need to be considered when hyperprolactinemia is evaluated. Pituitary adenomas are the most common cause of chronic hyperprolactinemia and need to be ruled out. Prolactin suppresses gonadotropin-releasing hormone agonist (GnRH) output and therefore can induce various ovulatory problems. In extreme cases -- that is, at significantly elevated levels -- prolactin can induce amenorrhea.

Several theories have been proposed to explain the etiology of PCOS. One of the theories posits that PCOS results from central neurotransmitter dysregulation, which leads to abnormal gonadotropin output and abnormal ovarian function. Altered dopamine turnover could result in hyperprolactinemia, could also affect GnRH output, and therefore could be a common cause for both PCOS and hyperprolactinemia. However, the incidence of hyperprolactinemia among women with PCOS should be higher if there is a common underlying neurotransmitter abnormality. So, it is more likely that hyperprolactinemia and PCOS are independent disorders.

Estrogen stimulates prolactin production. Persistently elevated estradiol levels are often found in women with PCOS and could result in mild prolactin elevation.

Several studies have reported higher incidence of hyperprolactinemia among PCOS patients. Most of these studies, however, were based on small numbers of patients and few serum measurements. In addition, various diagnostic criteria were used to define PCOS.

Hyperprolactinemia has to be ruled out to make the diagnosis of PCOS. Therefore, work-up of persistent hyperprolactinemia is necessary. Physiologic causes, drug effects, and pituitary lesions need to be considered. Once the evaluation is complete, treatment needs to be aimed at the clinical problem. If the problem is infertility, the course of action is to induce ovulation with the addition of dopamine agonist. If the problem is hyperandrogenemia or irregular bleeding, then estrogen-progesterone preparations can be used, but one needs to be aware of their effect on prolactin secretion. A similar approach should be followed in the research setting. PCOS patients with mild hyperprolactinemia should only be included in studies when other possible etiologies have been ruled out.


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