Hyperprolactinemia/Prolactinomas in the Postmenopausal Period: Challenges in Diagnosis and Management

Abstract

Hyperprolactinemia is not a common finding in postmenopausal women. Prolactinomas detected after menopause are usually macroadenomas. Due to atypical clinical features they may remain unrecognized for a long period of time. Interestingly the growth potential of prolactinomas remains after menopause. Most tumors are invasive and present with high prolactin levels. They respond to medical treatment with dopamine agonists in terms of prolactin normalization, tumor shrinkage, and improvement in pituitary function. Treatment with dopamine agonists is usually long term. Reducing doses of cabergoline to the lowest that keeps prolactin levels normal prior to withdrawal is proposed to patients with macroprolactinomas who normalize prolactin after > 5 years of treatment and who do not have cavernous sinus invasion. Cabergoline can achieve a high percentage of remission maintenance in the first years after withdrawal. However, the percentage of relapse-free patients 5 years after withdrawal is significantly lower. Besides recurrent hyper­prolactinemia in a subgroup of macroprolactinomas after a long-interval tumor regrowth may be detected. Menopause cannot ensure remission of the tumor so long-term surveillance is suggested. In patients with microadenomas data on long-term remission rates (normalization of prolactin and disappearance of the tumor) after suspension of treatment with dopamine agonists are highly variable. The current strategy for microprolactinomas is not to treat hyperprolactinemia in menopause if it recurrs after discontinuation of dopamine agonists. This is based on: (1) reports that elevated prolactin levels may normalize in some women after menopause, (2) the fact that the association between prolactin levels and breast cancer is inconsistent in postmenopausal women, (3) the lack of clinical evidence that normalization of prolactin levels in postmenopausal women improves bone mineral density or reduces the risk of fracture, and (4) the fact that, concerning the metabolic syndrome, no data are available on metabolic parameters after suspension of treatment with dopamine agonists. For a change in strategy, i.e., for the potential benefits from treatment of hyperprolactinemia in the postmenopausal period with dopamine agonists concerning weight loss, improved insulin sensitivity, decreased fracture risk, and improved sexuality, more evidence is needed.

Pituitary Hyperplasia, Hormonal Changes and Prolactinoma Development in Males Exposed to Estrogens—An Insight From Translational Studies

“…Similar prevalence, but a higher incidence of pituitary prolactinoma formation is observed in women at a younger age in comparison with men [7,8] and disappears after menopause [9]. Moreover, male patients have a higher serum PRL level and larger tumor volume in comparison with female patients with prolactinoma [10,11].…”

Hyperprolactinemia in the postmenopause: versions and contraversions

“…Большинство женщин с существующим диагнозом пролактиномы после менопаузы не предъявляли специфических жалоб. Надо признать, что обследование анализа крови на ПРЛ регламентируется клиническими симптомами (нарушения менструальной и репродуктивной функции, галакторея), и, соответственно, вероятность такого скрининга присутствует у женщин с менструальной функцией [9]. Тем не менее во многих случаях длительная задержка диагностики пролактином и ГПРЛ у женщин может быть связана с использованием гормональных контрацептивов (регулярные циклы, несмотря на ГПРЛ) или внутриматочных устройств с левоноргестрелом, поэтому врачи не всегда могут полагаться на гонадные эффекты ГПРЛ [10][11][12].…”

“…Задержка в диагностике гигантских пролактином у женщин составляла от 2 до более 30 лет [11]. И еще одна непостоянная находка у женщин с макропролактиномами -галакторея (37,5%) [9,12]. Однако данные относительно галактореи могут быть недооценены, поскольку многими врачами не регистрируются.…”

Glucose Abnormalities Associated to Prolactin Secreting Pituitary Adenomas

“…In such patients, the treatment with dopamine agonists might induce a direct remarkable improvement of gluco-insulinemic profile. The amelioration of glucose homeostasis abnormalities and metabolic syndrome could be even more relevant in women in the postmenopausal period, when weight loss and improved insulin sensitivity might contribute to reduce cardiovascular risk (72). Therefore, the treatment with cabergoline might be maintained in menopausal women regardless from PRL levels in order to retain the beneficial action of dopamine agonists on metabolic profile.…”