Spanish consensus on the risks and detection of antipsychotic drug-related hyperprolactinaemia: Is there convergence with other clinical guidelines for the management of hyperprolactinaemia?

In a recently published expert consensus on hyperprolactinaemia,¹ treating levels of prolactin higher than 50 ng/ml or levels with clinical impact is recommended. For levels higher than 100 ng/ml, it is specified that these cases should always receive intervention even though there is no amenorrhea-galactorrhea, because of the medium/long-term risk of osteoporosis, cardiovascular disease and possible increase in factors of risk for breast or endometrial cancer.

It is surprising to see that some recommendations depart from other national and international clinical guidelines that recommend treating only symptomatic hyperprolactinaemia. For example, other clinical guidelines for managing hyperprolactinaemia that include drug-related hyperprolactinaemia, such as those of the expert consensus from the Endocrine Society² and the Spanish Society of Endocrinology and Nutrition (Spanish acronym: SEEN),³ recommend not treating asymptomatic hyperprolactinaemia. The indication for treatment based on the choice of a cut-off point in the analytical analyses, as recommended in this recent consensus,¹ departs from other clinical guidelines developed by endocrinology societies.

An important aspect of managing antipsychotic-drug-related hyperprolactinaemia is controlling bone mass and establishing preventative measures to avoid the risk of osteoporosis. A strategy that should be evaluated in cases with chronic hypogonadism (symptoms of hypogonadism or decreased bone mass) is administration of estrogen or testosterone supplements. This therapeutic option (recommended in the guidelines of both the la Endocrine Society² and the SEEN³) has only been developed slightly in the Spanish consensus, which focuses more on intervening in the antipsychotic treatment.

As for the role of hyperprolactinemia in the risk of some cancers, such as breast cancer, this is a controversial matter. Although in vitro studies suggest that prolactin stimulates cellular proliferation, survival and migration of cancerous breast cells,^4,5 systematic reviews and meta-analyses of human-based studies suggest that there is no relationship between hyperprolactinaemia and breast cancer risk.^6,7 Given that there is a local secretion of paracrine-form prolactin (dopamine independent), the studies that have explored prognostic aspects of breast cancer at tissue level cannot be extrapolated to the effects of systemic hyperprolactinaemia (plasma levels of elevated prolactin). Besides, in some of the studies reporting associations between prolactin levels and breast cancer, such as in the EPIC cohort,⁸ the relationship is limited to the women receiving hormone replacement therapy (RHT) at the time of the study. Because RHT is a known risk factor for breast cancer,⁹ it is consequently a poor idea to generalize the results on prolactin figures in a subsample of patients receiving this treatment to the population of patients with schizophrenia that receive antipsychotic treatment. As some authors defend,⁷ other risk factors for breast cancer such as nulliparity, obesity, diabetes mellitus and an unhealthy life style (drug, alcohol or tobacco use, limited physical activity) probably play a more relevant role than prolactin if we focus on the risk of breast cancer in women with schizophrenia.

I completely agree with the consensus on the importance of controlling complications of chronic hyperprolactinaemia, such as hypogonadism, the risk of osteoporosis (by performing bone densitometries) and sexual dysfunction. In many cases, these adverse effects are present but not evident unless they are explored in detail. For this reason, it is important to act at the therapeutic point of view considering the impact of hyperprolactinaemia on each patient (especially in the case of symptomatic hyperprolactinaemia) instead of placing a prolactin plasma value above this. Considering the current scientific evidence, we should be prudent when generating conclusions about some risks such as the association between antipsychotic drug-related hyperprolactinaemia and the risk of cancer, because the studies on this matter show inconsistent results.

Conflicts of interest

Dr. Javier Labad has been a consultant for or has received fees or research funding from Otsuka, Lundbeck and Janssen-Cilag.