ORIGINAL RESEARCH
ORIGINAL RESEARCH–ENDOCRINOLOGY: Hypoprolactinemia: A New Clinical Syndrome in Patients with Sexual Dysfunction

https://doi.org/10.1111/j.1743-6109.2008.01206.xGet rights and content

ABSTRACT

Introduction

The physiological role of prolactin (PRL) in male sexual behavior is poorly understood. Conversely, the association between PRL pathological elevation in both reproductive and sexual behavior is well defined.

Aim

The aim of the present study is to assess the correlates of normal PRL (PRL < 735 mU/L or 35 ng/mL), in male subjects consulting for sexual dysfunction.

Methods

A consecutive series of 2,531 (mean age 52.0 ± 12.9 years) subjects was investigated. Patients were interviewed using the structured interview on erectile dysfunction (SIEDY), a 13-item tool for the assessment of erectile dysfunction (ED)-related morbidities. Middlesex Hospital Questionnaire was used for the evaluation of psychological symptoms.

Main Outcome Measures

Several hormonal (testosterone, thyroid stimulation hormone, and PRL) and biochemical parameters (glycemia and lipid profile) were studied, along with penile Doppler ultrasound (PDU) and SIEDY items.

Results

After adjustment for confounders anxiety symptoms decreased across PRL quartiles (I: <113 mU/L or 5 ng/mL; II: 113–156 mU/L or 5.1–7 ng/mL; III: 157–229 mU/L or 7.1–11 ng/mL; IV: 229–734 mU/L or 11.1–34.9 ng/mL). Patients in the lowest PRL quartile showed a higher risk of metabolic syndrome (MetS; odds ratio [OR] = 1.74 [1.01–2.99], P < 0.05), arteriogenic ED (peak systolic velocity at PDU < 35 cm/sec; OR = 1.43 [1.01–2.03], P < 0.05), and premature ejaculation (PE; OR = 1.38 [1.02–1.85]; P < 0.05). Conversely, comparing subjects with PRL-secreting pituitary adenomas (N = 13) with matched controls, no significant difference was observed, except for a higher prevalence of hypoactive sexual desire in hyperprolactinemia.

Conclusions

Our findings demonstrate that, in subjects consulting for sexual dysfunction, PRL in the lowest quartile levels are associated with MetS and arteriogenic ED, as well as with PE and anxiety symptoms. Further studies are advisable in order to confirm our preliminary results in different populations. Corona G, Mannucci E, Jannini EA, Lotti F, Ricca V, Monami M, Boddi V, Bandini E, Balercia G, Forti G, and Maggi M. Hypoprolactinemia: A new clinical syndrome in patients with sexual dysfunction. J Sex Med 2009;6:1457–1466.

Introduction

Prolactin (PRL) is a 23 kDa-polypeptide secreted by pituitary lactotroph cells, under negative dopaminergic and positive serotoninergic control [1]. PRL was first discovered in 1933 by Riddle et al. [2]. Quite surprisingly, 75 years later, the physiological role of PRL in males is still poorly understood. Conversely, the association between PRL pathological elevation and derangements in both reproductive and sexual behavior is well defined 3, 4, 5. The prevalence of mild hyperprolactinemia (PRL > 420 mU/L or 20 ng/mL) in male subjects with sexual dysfunction is quite variable, ranging from more than 13% [6] to less than 2% 3, 7. In these subjects, severe hyperprolactinemia (SHPRL; PRL > 735 mU/L or 35 ng/mL) is a relatively rare event (less than 1%; 3, 5). Milder forms of hyperprolactinemia do not play a significant role in the pathogenesis of male sexual dysfunction 3, 5. Conversely, SHPRL has a negative impact on sexual function, impairing sexual desire—as well as erectile function—and testosterone production 3, 4, 5, 8, 9. We previously demonstrated that in subjects with sexual dysfunction, a severely reduced libido is associated with a 10-fold increase in the prevalence of SHPRL [5]. A PRL-induced hypogonadism could explain, at least partially, this association [5]. PRL plays also a direct role in the control of male sexual desire. Among hypogonadal subjects with hyperprolactinemia, PRL-lowering drugs are able to restore both testosterone levels and libido 5, 9, while testosterone replacement therapy is not as effective [10].

The relationship between hyperprolactinemia and erectile function is under debate. Some authors have suggested a possible pathogenetic link between severe erectile dysfunction (ED) and SHPRL 4, 11. However, in agreement with others [6], we were not able to confirm this finding, after adjustment for confounders [5]. In addition, controlled studies evaluating the effect of dopamine agonists on ED subjects with hyperprolactinemia were inconclusive [9].

Finally, even a perturbation of ejaculatory control has been reported in subjects with hyperprolactinemia. In particular, El-Sakka et al. [6] reported a significantly higher prevalence of premature ejaculation (PE) in subjects with mild hyperprolactinemia. The reasons of such association are unclear.

Section snippets

Aim

The aim of the present study is to assess the role of low-to-normal levels of PRL in subjects consulting for sexual dysfunction. Furthermore, a direct comparison of the clinical and biochemical features of subjects with PRL-secreting pituitary adenomas with those of matched controls will also be provided.

Methods

A consecutive series of 2,531 male patients attending the outpatient clinic for sexual dysfunction for the first time (from January 2001 to April 2008) was studied. Patients with mental retardation, or not fluent in Italian, were excluded. The socio-demographic and clinical characteristics of the sample are summarized in Table 1. An informed consent for the study was obtained from all patients. All patients enrolled underwent the usual diagnostic protocol applied to newly referred subjects at

Main Outcome Measures

All patients underwent a complete physical examination, with measurement of blood pressure (mean of three measurements 5 minutes apart, in sitting position, with a standard sphygmomanometer), height, weight, waist, and testis volume (Prader orchidometer). Blood samples were drawn in the morning, after an overnight fast, for determination of blood glucose (by glucose oxidase method, Aeroset Abbott, Rome, Italy) total and high density lipoprotein cholesterol, and triglycerides (by automated

Results

Among patients studied, 2,265 (89.5%) reported ED, 929 (36.7%) HSD, 658 (26.0%) PE, and 165 (6.5%) DE. Among patients with PE, 241 (36.6%) reported an acquired problem (present for at least 3 months) while 417 (63.4%) reported a lifelong problem. Hyperprolactinemia (PRL > 720 mU/L or 35 ng/mL) was detected in 35 cases (1.4%). Among patients with hyperprolactinemia, three showed macroprolactinemia. Of the other 32 subjects, nine were affected by microprolactinoma, six by macroprolactinoma, six

Discussion

We report here, for the first time, that among males consulting for sexual dysfunction, hypoprolactinemia (i.e., PRL levels in the lowest quartile) is associated with particular psychobiological features, including a higher prevalence of MetS and arteriogenic ED, as well as PE and anxiety symptoms. Different central and peripheral mechanisms could be advocated to explain these associations. In fact, low PRL could mirror an increase of central dopaminergic tone or an impaired central

Conclusions

Our findings demonstrate that, in subjects consulting for sexual dysfunction, low PRL levels are associated with MetS and arteriogenic ED, as well as with PE and anxiety symptoms. Further studies are advisable in order to confirm our preliminary results in different populations.

Acknowledgments

We would like to thank Angela Magini, Riccardo Mansani, Csilla Krausz, and Luisa Petrone of the Andrology Unit of the University of Florence.

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