Hypersexuality in men with prolactinomas treated with dopamine agonists

Abstract

Prolactinoma is the most common hypersecreting tumor of pituitary gland [1] and medical therapy with dopamine agonists (DAs) is recommended as first line intervention. DA therapy is effective in reversing hyperprolactinemia and its consequences-secondary hypogonadism and galactor-rhea and may induce tumor shrinkage [2]. DA, such as cabergoline and bromocriptine, lead to prolactin normal-ization by acting through D2 receptors on the lactotroph cells. In many cases DA therapy is necessary for extended period of time, even lifelong. While more common side effects of DAs such as headaches, dizziness and gastro-intestinal disturbance are well known, a less recognized side effect of DA therapy is development of impulse control disorders (ICDs). ICDs include hypersexuality, gambling, punding, compulsive shopping and binge eating and are thought to be mediated through dopamine receptors in the reward pathways of the mesolimbic system [3]. In a case-control study of 77 patients with DA treated prolactinomas and 70 patients with non-functioning pituitary tumors, prevalence of ICDs was reported to be 25 and 17%, respectively [4]. However, striking differences were observed only for men in the DA treated-prolactinoma group who were almost 10 times more likely to develop an ICD when compared to men with non-functioning pituitary adenomas [4]. Moreover, authors noted a between-group significant difference only for hypersexuality which affected 10 patients (7 men) [4]. In the current report, De Souza et al. describe findings in 8 men with DA treated prolactinomas identified from their clinics who developed hypersexuality. Authors suggest that a synergy between DA therapy and restoration of eugonadal state may contribute to development of hypersexuality and propose the term "dopa-testotoxicosis" to describe these occurrences [5]. In their case series, men developed hypersexuality within days to years after commencing DA therapy and this coincided with normalization of prolactin and improvement of testosterone concentrations. Interestingly , though hypersexuality was a predominant ICD, both Bancos et al. and De Souza et al. reported that a third of patients in their cohort (7/19 and 2/8, respectively) developed multiple ICDs [4, 5]. The term "dopa-testotoxicosis" does not account for ICD development other than hyper-sexuality, or the development of hypersexuality in women. In addition, it is difficult to draw conclusions that a relative increase in testosterone concentrations (as none of the patients had supraphysiological testosterone concentrations) played a major contribution to developing hypersexuality, especially, given the design of both studies. Prospective studies are needed to reveal any temporal relationship to testosterone concentrations and to define any other predis-posing factors to developing hypersexuality and other ICDs. Based on the published case reports of hypersexuality reported in patients with DA treated prolactinomas, severity of presentation varies, but can be devastating to patients and their families....

Dopamine agonist therapy for prolactinomas: do we need to rethink the place of surgery in prolactinoma management?

“…In one of the early case series of DA-induced ICDs in hyperprolactinaemic patients, we proposed the term ‘dopa-testotoxicosis’ to highlight the male predilection and hypersexuality predominance in DA-induced ICDs in the prolactinoma setting ( De Sousa et al 2017 ). This prompted debate in the literature as to the role of testosterone in contributing to hypersexuality in this context ( Bancos et al 2017 , Athanasoulia-Kaspar et al 2018 , Barake et al 2018 , Celik et al 2018 , Dogansen et al 2019 , Ioachimescu et al 2019 ). We subsequently explored this association and other potential risk factors in a large cross-sectional analysis of 113 hyperprolactinaemic patients vs 99 healthy controls.…”

“…However, aripiprazole also has agonist activity at the D3 receptor, and the aforementioned FDA study found an increased risk of ICDs in aripiprazole-treated individuals ( Moore et al 2014 ). Dose reduction or switching to another DA has also been suggested in the management of DA-induced ICDs as lowering the dose in particular may reduce ICD symptoms ( Bancos et al 2014 , 2017 , De Sousa et al 2017 , Celik et al 2018 , Dogansen et al 2019 ). However, this is not substantiated by other data showing that the risk of ICD development is not associated with DA type or dose ( Martinkova et al 2011 , Bancos et al 2014 , De Sousa et al 2017 , 2019 a , Celik et al 2018 , Dogansen et al 2019 ).…”

Compulsive sexual behaviour in Iranian married women: Prevalence, sociodemographic, sexual, and psychological predictors across-country

“…Irina and Garnik's study supports this, linking joblessness and increased free time to excessive sexual behaviors. Moreover, unemployment may contribute to depression and reduced self-esteem, further elevating the risk of engaging in hypersexuality as a coping mechanism (Bancos, Nippoldt, & Erickson, 2017;Коcharyan, 2019). Among sexual history characteristics, the use of pornography, paraphilic behaviours, and conflict in sex frequency have a positive relationship with CSBD.…”

Hypersexuality as a tip of the iceberg of a primary psychopathology: a joined position statement of the Italian Society of Andrology and Sexual Medicine (SIAMS) and of the Italian Society of Psychopathology (SOPSI)

“…Several risk factors have been identified, such as male gender, young age, and presence of psychiatric comorbidities. Dopamine agonists are also commonly used in the endocrinological setting as a first-line treatment for PRL-secreting adenomas (prolactinomas), although at a much lower dosage (Table 1), [86]. Even at such dosages, however, impulse control disorders may appear: while their prevalence is debated due to different measurement tools, impulse control disorders are significantly more common in prolactinoma/hyperprolactinemia patients treated with dopamine agonists than healthy controls [87].…”