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Effects of Acute Prolactin Manipulation on Sexual Drive and Function in Males

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Effects of Acute Prolactin Manipulation on Sexual Drive and Function in Males 357 Effects of acute prolactin manipulation on sexual drive and function in males T H C Krüger, P Haake, J Haverkamp, M Krämer, M S Exton, B Saller1, N Leygraf2, U Hartmann3 and M Schedlowski Department of Medical Psychology, University of Essen, Hufelandstrasse 55, 45122 Essen, Germany 1Division of Endocrinology, Department of Medicine, University of Essen, 45122 Essen, Germany 2Department of Forensic Psychiatry, University of Essen, 45122 Essen, Germany 3Department of Clinical Psychiatry, Hanover Medical School, 30625 Hanover, Germany (Requests for offprints should be addressed toTHCKrüger; Email: [email protected]) Abstract The neuroendocrine response to sexual activity in humans Administration of cabergoline decreased prolactin levels is characterized by a pronounced orgasm-dependent and significantly enhanced all parameters of sexual drive increase of plasma levels of prolactin. In contrast to (P,0·05), function (P,0·01) and positive perception of the well-known inhibitory effects of chronic hyperpro- the refractory period (P,0·01). Administration of pro- lactinemia on sexual drive and function, the impact of tirelin increased prolactin concentrations and produced acute prolactin alterations on human sexual physiology is small, but not significant reductions of sexual parameters. unknown. Therefore, this study was designed to investi- The sexual effects observed from cabergoline were gate the effects of acute manipulation of plasma prolactin completely abrogated by coadministration of protirelin. on sexual behavior. Although different pharmacological sites of action of Ten healthy males participated in a single-blind, prolactin-altering drugs have to be considered, these data placebo-controlled, balanced cross-over design. Prolactin demonstrate that acute changes in prolactin plasma levels levels were pharmacologically increased to high levels may be one factor modulating sexual drive and function. (protirelin, 50 µg i.v.) or reduced to low physiological Therefore, besides a neuroendocrine reproductive reflex, a concentrations (cabergoline, 0·5 mg p.o.). Sexual arousal post-orgasmic prolactin increase may represent one factor and orgasm were then induced by an erotic film and modulating central nervous system centers controlling masturbation. In addition to continuous neuroendocrine sexual drive and behavior. These findings may offer a new and cardiovascular recordings, the quality and intensity of pharmacological approach for the treatment of sexual the acute sexual drive, arousal, orgasm and refractory disorders. period were assessed by extensive psychometric measures. Journal of Endocrinology (2003) 179, 357–365 Introduction of sexual stimulation, including films, masturbation and coitus in both men and women. This series of studies have The characterization and relevance of the neuroendocrine consistently demonstrated that plasma prolactin concen- response to human sexual activity has received little trations are substantially increased following orgasm in scientific attention. Previously, large methodological dif- both men and women, but unchanged following sexual ferences in inducing sexual activity (viewing of stimulating arousal without orgasm (Krüger et al. 1998, 2003, films, imagery of fantasies, masturbation, coitus), collecting M S Exton et al. 1999, 2001a, N G Exton et al. 2000). blood samples (blood sampling at single discrete time Furthermore, elevations of prolactin following orgasm points) and the experimental setting (examination cabin, remain increased over the experimental session, and investigator entering the room) have resulted in hetero- remain raised 60 min following sexual arousal. geneous data regarding the acute neuroendocrine response There is clinical and experimental evidence suggest- pattern to sexual arousal, thereby ensuring that this ing that the prolactin response to orgasm may not only phenomenon is poorly understood (Meston & Frolich affect reproductive organs (Outhit et al. 1993, Bole-Feysot 2000, Krüger et al. 2002). et al. 1998, Goffin et al. 1999), but also play a role in Therefore, we developed a model to record continu- the control of acute sexual arousal following orgasm. ously the neuroendocrine response to various forms Supporting this position, chronic elevations of prolactin Journal of Endocrinology (2003) 179, 357–365 Online version via http://www.endocrinology.org 0022–0795/03/0179–357 2003 Society for Endocrinology Printed in Great Britain Downloaded from Bioscientifica.com at 09/29/2021 01:01:23AM via free access 358 THCKRU}GER and others · Prolactin and sexual behavior (hyperprolactinemia), induced by prolactin-secreting questionnaire to exclude individuals taking medication, tumors or as a side effect of typical neuroleptics, produce abusing drugs/alcohol, exhibiting endocrinological or pronounced reductions of sexual drive and gonadal func- psychological disorders or fulfilling any contraindication tions in animals (Doherty et al. 1986) and humans (Yazigi for the administration of protirelin or cabergoline. et al. 1997, Hummer et al. 1999, Knegtering et al. 2003). Additionally, a questionnaire for the evaluation of sexual Importantly, these effects are reversed upon pharmaco- problems/dysfunctions in males was employed. Further- logical or surgical restoration of normal prolactin levels more, subjects were screened for psychogenic erectile (Verhelst et al. 1999). We therefore proposed a theoretical dysfunction by questionnaire of the dual control model of model suggesting that orgasm-induced prolactin release male sexual response (Bancroft & Janssen 2000). Subjects may modify dopaminergic systems within the central did not show any significant differences in the specific nervous system (CNS) that are responsible for controlling subscales (sexual inhibitory and excitatory scale) in sexual drive and refractoriness (Krüger et al. 2002). Besides comparison with a normative sample of healthy males. a short-loop feedback to tuberoinfundibular dopaminergic Subjects underwent a semi-structured interview and a neurons regulating pituitary prolactin release (DeMaria physical examination by a research physician. All partici- et al. 1999), peripheral prolactin may be able to affect pants were sexually active and reported an exclusively dopaminergic neurons in the nigrostriatal and mesolimbo- heterosexual orientation and a relaxed attitude towards cortical system and the medial preoptic area. Animal masturbation and erotic films. Subjects reported an average studies have demonstrated that these sites are responsible refractory period of 18·432·30 min. for the regulation of genital responses, appetitive behavior and motor activity (Hull et al. 1999, Krüger et al. 2002). Although prolactin is not able to pass the blood–brain Design and procedure barrier due to its size (199 amino acid peptide), it may The investigation was performed using a single-blind, reach these areas via the blood–CSF barrier and the placebo-controlled, balanced cross-over design. A circumventricular organs (Gangong 2000, Sobrinho repeated measures design was used so that each subject 1993). participated in four experimental sessions in a different To elucidate the function of orgasm-induced prolactin order, experiencing the conditions of: lowered prolactin, secretion in humans, we here analyzed the effects of acute elevated prolactin, blunted prolactin (coadministration of pharmacological manipulations of prolactin plasma levels both drugs), and unaltered prolactin (placebo); further, on sexual arousal, orgasm and the refractory period in subjects participated in a control session where a docu- healthy young males, utilizing a single-blind, placebo- mentary film was shown. In total, each subject participated controlled cross-over study design. Using the established in five examinations. All sessions took place at 1600 h experimental paradigm (Krüger et al. 2002), prolactin (Fig. 1). A one week interval separated each session, with levels were altered to either high or low physiological the exception of the low-prolactin session, which was concentrations. Additionally, immediately after the 60 min followed by an interval of one month due to long-lasting session a second orgasm was induced by a pornographic effects of the prolactin-lowering drug cabergoline in few film. This allowed examination of the subjects’ refractory persons (Andreotti et al. 1995). period and the ability to reinitiate sexual activity. In Experiments were conducted in a separate sound- addition to measurement of cardiovascular and neuro- attenuated room equipped with a reclining armchair, a endocrine parameters, variables of sexual drive and func- color television and a video cassette player. All leads, tion were evaluated using a questionnaire that has been including the blood line, passed through the wall into the specifically developed for the assessment of acute sexual adjacent room where the cardiovascular data and blood experiences in a laboratory setting. samples were collected, allowing subjects to be completely isolated throughout the entire experiment. At the begin- ning of the experiments subjects positioned themselves in Materials and Methods the armchair in front of the screen. The cardiovascular monitor was then engaged 20 min prior to the film and a Subjects steady baseline reading was obtained before the cannula Ten healthy males (mean age 25·92·5 years, age range was inserted (15 min before the film). Depending on the 22–31 years) participated in this study after providing condition, prolactin-altering drugs or NaCl were then written informed
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