Choline Associated Hypersexuality in a 79-Year-Old Man
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- Calabrò, R.S., Cordici, F., Genovese, C. et al. Arch Sex Behav (2014) 43: 187. doi:10.1007/s10508-013-0137-6
Hypersexuality, also referred to as sexually inappropriate behavior and sexual disinhibition, involves persistent, uninhibited sexual behaviors directed at oneself or at others, sometimes associated with neurodegenerative disorders. Choline is a water-soluble essential nutrient, used as a dietary supplement in different diseases. This report was aimed at considering choline intake as a possible cause of iatrogenic hypersexuality. After an evaluation, a 79-year-old man affected by memory loss was diagnosed with mild cognitive impairment and treated with oral choline. After 6 weeks of regular choline assumption, the patient showed a pathological increase in libido with sexual urges. As choline was withdrawn, the hypersexuality disappeared within 5 days. Since hypersexuality may be an underreported and overlooked adverse effect of drugs and dietary supplements acting on the cholinergic pathway, this should be considered when treating and counselling patients with inappropriate sexual behavior.
KeywordsCholineHypersexualityMild cognitive impairmentNeurodegenerative disorders
Sexuality is dependent on many factors, including individual and relationship variables, societal values, cultural mores, ethnic and religious beliefs, and biological factors. Although there is no universally accepted definition of hypersexuality, health professionals working in this area have emphasized the concepts of frequency and sudden change as important characteristics. Additional ways of assessing hypersexuality might include social appropriateness of expressed behavior and the degree to which the altered sexuality is within or outside of 2 SDs from age-controlled norms.
To this end, Kafka (2010) proposed to refer to “Hypersexual Disorder” as a sexual desire disorder characterized by an increased frequency and intensity of sexually motivated fantasies, arousal, urges, and enacted normophilic behavior in association with an impulsivity component, i.e., a maladaptive behavioral response with adverse consequences. Although hypersexual behaviors are typically associated with dysphoric affects, such as anxious or depressive mood, irritability, and boredom, hypersexuality may be associated with neurodegenerative disorders or with brain injury (Kaplan & Krueger, 2010).
The most commonly documented physiological findings associated with hypersexual behavior are frontal and temporal lobe lesions and trauma. Indeed, frontal lobe dysfunction impairs inhibitory sexual self-control mechanisms, whereas temporal lobe dysfunction impairs emotional and intellectual understanding of sexual arousal (Nagaratnam & Gayagay, 2002; Wallace & Safer, 2009).
Choline is a water-soluble essential nutrient, grouped within the B-complex vitamins, used as a dietary supplement in different diseases, including liver, psychiatric, and neurological disorders (Ueland, 2011). Mild cognitive impairment (MCI) refers to the transitional state between the cognitive changes of normal aging and very early dementia. Indeed, several population and community-based studies have documented an accelerated rate of progression to dementia and Alzheimer’s disease (AD) in individuals diagnosed with MCI. Initiating treatment and care management in the MCI phase could improve the health and well-being of patients and caregivers. Thus, different treatment strategies, including choline precursors and cholinesterase inhibitors, have been used to prevent this possible transition (Petersen & Negash, 2008).
Herein, we report on an elderly male patient affected by MCI, who experienced a pathological increase in libido after choline intake.
An otherwise healthy 79-year-old man came to our clinic for memory loss. Neurological examination, hematochemical tests, including blood cell count, coagulation, autoimmunity markers, thyroid hormones, homocysteine, vitamins and folate and brain CT were within the normal range. Neuropsychological evaluation showed an isolated deficit in short term memory with no functional impact on daily activity: the Mini-mental State Examination (MMSE) showed a 28/30 score. Thus, MCI diagnosis was supposed and oral choline supplementation (i.e., choline alphoscerate, a precursor of the phosphatidylcholine) was prescribed at a dosage of 1200 mg/day.
After 6 weeks of regular choline ingestion, the patient showed a significant increase in libido with sexual urges, even in inappropriate places. His wife, a healthy 70-year-old woman, said that her husband had unexpectedly changed his sexual behavior: they usually had regular sexual intercourse no more than once a month, but, in the last weeks, he wanted to engage her in sexual activity at least three times a day and often asked her for oral sex.
Moreover, the patient was very annoyed and nervous when his wife refused sexual contacts; thus, he started masturbating “to alleviate his psychological discomfort.”
Interestingly, while on choline, the patient and his wife reported a significant improvement in erectile function. Because of this abnormal sexual behavior, choline was withdrawn and hypersexuality receded after about 5 days.
Before choline discontinuation, the patient’s sex hormone levels, including total (7 ng/ml) and free testosterone (0.14 ng/ml), were within the normal range. Intriguingly, since the patient was “proud” of his sexual potency while on choline, he spontaneously and secretively ingested oral choline for about another month with a consequent hypersexuality.
The patient resumed his “normal” sexual behavior after complete withdrawal of choline intake.
The prevalence of sexual activity declines with age, yet a substantial number of men and women engage in vaginal intercourse, oral sex, and masturbation even in the eighth and ninth decades of life. A study by Lindau et al. (2007) reported that the frequency of sex was lower among U.S. adults between 75 and 85 years old than among younger persons (73 % among participants who were 57–64 years of age, 53 % among participants who were 65–74 years of age, and 26 % among participants who were 75–85 years of age); women were significantly less likely than men to report sexual activity at all ages. However, even in the oldest age group, 54 % of sexually active persons reported having sex at least two to three times per month, and 23 % reported having sex once a week or more.
Hypersexuality, also referred to as sexually inappropriate behavior and sexual disinhibition, involves persistent, uninhibited sexual behaviors directed at oneself or at others. The literature generally attributes the abnormal behavior of older adults to biochemical or physiological changes that accompany cognitive impairment, specifically dementia. Although less common than other behavioral issues associated with dementia, such as aggression and agitation, hypersexuality may manifest itself through a change in an individual’s sexual appetite, preferences, and capabilities (Nagaratnam & Gayagay, 2002). However, limited research and inconsistent definitions have resulted in large variations in the prevalence of reported hypersexual behaviors among cognitively impaired older adults, ranging between 2 and 30 % (Wallace & Safer, 2009).
Although hypersexuality is a relatively common side effect of dopamine agonists (Kelley, Duker, & Chiu, 2012), only sporadic cases of other drug-induced hypersexuality, suggesting an important role of norepinephrine in sexual function, have been described so far (Lai, 2010; Shapiro, Chang, Munson, Okun, & Fernandez, 2006).
To the best of our knowledge, this is the first report on choline-related hypersexuality. Because of its wide-ranging roles in human metabolism, from cell structure to neurotransmitter synthesis, choline-deficiency is now thought to have an impact on diseases such as liver disease, atherosclerosis, and, possibly, neurological disorders (Ueland, 2011). Indeed, the observation of a loss of cholinergic function in neocortex and hippocampus in AD formulated the hypothesis that replacement of cholinergic function may be of therapeutic benefit to AD patients.
The different approaches proposed or tested included intervention with acetylcholine (ACh) precursors, stimulation of ACh release, use of muscarinic or nicotinic receptor agonists and acetylcholinesterase (AChE) inhibition (Amenta, Parnetti, Gallai, & Wallin, 2001). In particular, as a modest improvement of cognitive dysfunction in dementia of neurodegenerative and vascular origin after treatment with phospholipids involved in choline biosynthetic pathways, such as cytidine 5′-diphosphocholine (CDP-choline) and choline alphoscerate is documented (Parnetti, Mignini, Tomassoni, Traini, & Amenta, 2007), we decided to treat our patient with oral choline.
Choline adverse effects, including variation in blood pressure, nausea, and dizziness, are extremely rare and mostly due to an overdose; no sexual side effects have been reported so far.
Choline is the precursor of acetylcholine, a parasympathetic neurotransmitter that facilitates genital blood flow engorgement: this peripheral mechanism of action may partially explain the patient’s improvement in erectile function. Nevertheless, it is also known that citicholine, a choline-derivate, helps the release of the neurotransmitter dopamine, which is directly involved in increasing libido (Agut, Ortiz, & Wurtman, 2000).
Interestingly, choline may be converted in trimethylglicyne (TMG) and dimethylglycine (DMG), which may be considered as “libido boosters” since they are involved, as methyl donors, in the metabolism of various hormones and neurotransmitters implicated in mood and sexual pleasure. Thus, this complex centrally-acting mechanism might play a key role in inducing hypersexuality in predisposed individuals. Indeed, as it becomes evident that single nucleotide polymorphisms (SNPs) in humans can create metabolic inefficiencies (Zeisel, 2011), it is possible that SNPs genes involved in acetylcholine (and/or other neurotransmitters) metabolism may have altered our patient’s choline response. Moreover, since testosterone levels were normal while the patient was on choline, a possible role of this sexual hormone in inducing the hypersexual behavior may be ruled out.
In conclusion, as hypersexuality may be an underreported and overlooked adverse effect of drugs and dietary supplements acting on the cholinergic and aminergic pathways in predisposed individuals, this should be considered when treating and counseling older patients with inappropriate sexual behaviors.