Director’s Note: Beyond prolactin’s role in lactation and menstruation, this hormone may play a key role in some uterine conditions. Below is the brief summary of a review article titled, “The Interplay Between Prolactin and Reproductive System: Focus on Uterine Pathophysiology.” [1] The article was published in 2020 by Auriemma et al and summarized by Dr. Spencer Ward while on the FACTS elective. The authors address implications of prolactin as a biomarker for uterine malignancy and discuss the impact of hyperprolactinemic states on fertility. For clinicians trained in fertility awareness-based methods (FABMs), this information highlights an additional tool in exploring potential root causes of infertility.
Introduction
In the article, “The Interplay Between Prolactin and Reproductive System: Focus on Uterine Pathophysiology,” Auriemma et al review recent research on the role of prolactin as both a potential biomarker and a therapeutic target for uterine malignancies, premalignancies, and benign uterine conditions. [1] This has broad implications for women’s health and may also play an important role in the diagnosis and treatment of infertility.
Clinical Implications of Prolactin’s Diverse Actions
Prolactin has widespread effects on many organ systems (its receptor is nearly ubiquitously expressed), but its greatest effects are on lactation and menstrual cycle inhibition. Although prolactin is primarily synthesized and secreted by lactotrophic cells of the anterior pituitary gland under inhibitory regulation by dopamine, it is also produced in peripheral sites like the endometrium and myometrium. This peripheral secretion has clinical applications, as uterine malignancies and premalignant lesions often increase serum prolactin levels. In these settings, prolactin can serve as a biomarker for malignancy.
“Although prolactin is primarily synthesized and secreted by … the anterior pituitary gland under inhibitory regulation by dopamine, it is also produced in peripheral sites like the endometrium and myometrium.”
Beyond the elevation of serum prolactin levels detected with some malignancies, prolactin has been implicated in the pathogenesis of uterine and cervical cancers. Prolactin receptors are highly expressed in uterine tumors and premalignant lesions; in rodents, prolactin has been shown to promote mammary tumor growth. Human ovarian epithelial cells have been shown to grow clones and lead to malignant transformation when exposed to chronic prolactin. For these reasons, prolactin has been hypothesized as a potential target when treating uterine malignancies. One method to reduce serum prolactin is by regulating its synthesis in the pituitary. Dopamine has an inhibitory effect on prolactin secretion, so medications like bromocriptine, a dopamine agonist, have been used in treatment. In one study, 18 patients with cervical carcinoma were treated with bromocriptine, and 45% showed cancer remission or stabilization.
Although studies show mixed results, prolactin has also been implicated in the pathogenesis of benign conditions like endometriosis and endometriosis-caused infertility. According to the authors, one study showed no correlation between prolactin and severity of endometriosis, while another showed the level of prolactinemia could discriminate both the presence and severity of the condition.
While current research is not adequate to determine the significance of this hormone in the pathogenesis of endometriosis, prolactin has been clearly shown to play a role in endometriosis-induced infertility. Dopamine agonists like bromocriptine may prove useful in the treatment of infertility secondary to endometriosis. Another medication, cabergoline, is useful in the treatment of endometriosis by reducing angiogenesis.
“Prolactin has been clearly shown to play a role in endometriosis-induced infertility. Dopamine agonists like bromocriptine may prove useful in the treatment of infertility secondary to endometriosis.”
Impact of Hyperprolactinemia
Auriemma et al also discuss hyperprolactinemic states and their implications on fertility. Prolactin release inhibits gonadotropin-releasing hormone (GnRH) secretion by the pituitary gland and decreases luteinizing hormone (LH) pulse frequency. It also has direct inhibitory effects on the ovaries, leading to decreased estrogen and progesterone synthesis. These effects can be beneficial, as in the case of breastfeeding postpartum mothers, but hyperprolactinemic states are also a cause of infertility. Whether from a prolactin-secreting adenoma or another source, hyperprolactinemia leads to cycle irregularities. Dopamine agonists are also beneficial in this setting. In fact, control of hyperprolactinemia via dopamine agonists has led to the return of ovulation and fertility in up to 90% of women treated.
“Prolactin release inhibits gonadotropin-releasing hormone (GnRH) secretion by the pituitary gland and decreases luteinizing hormone (LH) pulse frequency… These effects can be beneficial, … but hyperprolactinemic states are also a cause of infertility.”
Conclusion
Auriemma et al wrote a compelling review of the different sources and effects of prolactin in various disease states and their implications for fertility. Hyperprolactinemia leading to anovulation has a clear impact on fertility, but this article highlighted many other causes of infertility that are sometimes overlooked. Malignancies not only affect a person’s overall health and mortality but can also impact fertility, which can be just as important to a patient. Endometriosis can be a huge burden for a woman both in terms of pain and how it affects her fertility.
Fertility awareness-based methods (FABMs) can help determine the cause of infertility, and this article provides some potential solutions. While they do not directly target uterine malignancies or other uterine conditions, dopamine agonists like bromocriptine seem to show strong promise in the treatment of disease. More research into the efficacy of these treatments and the pathophysiologic effects of prolactin could prove beneficial in the lives of many struggling with infertility and other women’s health issues.
Editor’s Note: Learn more about the relationship between prolactin and reproductive health in these summaries written by students on the FACTS elective:
