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It is unlikely that such mild HPRLs were the real cause of ED, since very few cases had a low T level or pituitary tumors [238] However two microadenomas were found in such cases by Johri et al [241] In addition, only 40% of such patients improved as regards their erectile function following treatment with bromocriptine [18] This rate approximates the placebo effect and the 40% success rate reported with bromocriptine in normoprolactinemic ED patients [242] Conversely bromocriptine restored normal erectile function in eight of 12 ED cases (67%) with serum PRL >35 ng/ml [18], which suggests a causative effect of HPRL in this category Every one of the four other patients, although still unable to penetrate their partners after restoration of normal PRL levels, reported improved libido and morning erections Two of them subsequently recovered normal erectile capacity following additional sexual counseling
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The macroprolactin problem
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When evaluating the association between HPRL and sexual dysfunction, it should also be considered that biologically inactive or biologically inert variants of PRL may be assayed by immunological assays It is
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Hormones, Metabolism, Aging, and Men s Health especially the case of the big and big big PRLs that have high molecular weights [243] With immunological assays, excessive secretion of macroprolactins resembles a classical HPRL, while it has in fact generally no pathological consequence Macroprolactinemias account for 10% [244] to 22% [245] of all HPRLs and are typically observed in otherwise normal individuals, mostly women with normal reproductive function despite high PRL levels, but also some ED patients in whom they seem coincidental [246,247] Many of these cases suffered from psychogenic impotence In such cases serum T is usually normal, as are computerized tomography (CT) scans and magnetic resonance imaging (MRI) of the hypothalamic pituitary area PRL-lowering agents are ineffective in improving sexual function, although the PRL level can be normalized Such a discrepancy should lead to PRL chromatographic analysis, or precipitation of the macromolecules with polyethylene glycol, in a laboratory which specializes in endocrinology, allowing identi cation of the macroprolactin However a diagnosis of macroprolactinemia in an ED patient should preclude neither MRI testing, since some cases are associated with pituitary adenomas, nor a trial of a PRL-lowering agent, since a biologic activity of the macroprolactin has been demonstrated at least in some women, including reversal of amenorrhea and infertility on dopamine-agonist therapy [221]
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Diagnosis of hyperprolactinemia in men with sexual dysfunction
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Some precautions are critical to avoid false HPRLs resulting from stress (especially from venepuncture) and meals Blood sampling must be performed fasting, following a 20-minute rest in a quiet place Any elevated PRL level must be checked again, if possible following catheter insertion 20 minutes before sampling, and after discontinuation of any drug likely to increase PRL (Table 186) In case of discrepancy between high serum PRL and a pattern of nonendocrine sexual dysfunction, the patient may be referred to an endocrinologist who will decide about the usefulness of a PRL chromatography As already discussed, the responsibility of mild HPRLs (20 35 ng/mL) in sexual dysfunction is questionable In this respect, the threshold of signi cant HPRL is probably in the region of 35 ng/mL or 550 U/mL (1 ng/mL = 21 U/mL)
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Etiologic diagnosis
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Drug-induced HPRL is the rst etiology to consider It is responsible for a signi cant proportion of HPRLs in men Many drugs may increase PRL (Table 186) The most common are antipsychotic agents Other medications include antidepressants, some antihypertensive agents, and drugs that increase bowel motility [251] HPRL may also be secondary to hypothyroidism, renal insuf ciency, cirrhosis, and chest injury (mild or moderate in all four conditions), and to any process compressing or interrupting the hypothalamic pituitary dopaminergic transmission This includes many types of hypothalamic and pituitary tumors Primary HPRL results from a primary defect of the dopaminergic inhibitory control of PRL secretion It may be idiopathic, but in many cases it is associated with PRL-secreting pituitary adenomas These, as the other types of hypothalamic or pituitary tumors, are likely to result in tumoral complications (visual disturbances or even blindness due to compression of the optic chiasma, and hypopituitarism, which may become life-threatening if decompensated) Consequently, any man with non-drug-induced HPRL, con rmed by a repeat PRL determination after blood sampling in appropriate conditions, must bene t from morphologic investigations of the
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