Effects on Sexuality
The sex-related impact of T in men has been demonstrated in two groups: (a) those who have been deprived of this hormone in a significant manner and who are hypogonadal as a result (the most extreme example of which is men who have been castrated—physically or chemically—for any reason and in varying degrees) and (b) those who are generally healthy (including their hormone levels, otherwise referred to as “eugonadal”).
The influence of androgens on sexual desire is particularly prominent and was summarized by Bancroft (26; pp. 92 – 93). From his studies on hypogonadal men, he concluded that within 3 – 4 weeks of androgen withdrawl: (i) sexual inter- est declines as measured by the frequency of sexual thoughts (ii) sexual activity appears to diminish (as a result of decreased sexual desire) but is more difficult to assess because of the confounding effects of a sexual partner, and (iii) the capacity for ejaculation disappears. When androgen replacement is given, these phenomena are reversed within 7 – 10 days. As well, the impact of androgen replacement on sexual desire is dose-related.
Fantasy (or imagery)-associated erections and nocturnal erections are both androgen-dependent, and cease as a result of androgen withdrawal. The fact that only certain aspects of erectile function are affected suggests that the impact in this area is indirect, that is, on the man’s central nervous system rather than directly on his genitalia. Segraves suggests that when a man experiences erectile dysfunction in the context of T deprivation, the origin of the difficulty can be described as “performance anxiety” superimposed on a biogenic desire disorder (27; p. 278).
Segraves and Balon summarize the impact of the therapeutic use of T in eugonadal men by saying that “a relatively low level … is sufficient to maintain normal sexual activity, and that there is no demonstrable relationship between sexual function and variations of testosterone above this threshold value” (22; p. 215).
Changes in Effects with Age
The mystery of what happens to T as men age is not easy to unravel and possibly involves three separate issues: changes in production, carrier proteins, and recep- tor sensitivity.
The decrease in normal levels of T with age (described previously) seems partly explained by a decrease in function of both testicular tissue (Leydig cells) and the pituitary-hypothalamic axis. However, a second factor explaining the diminution may be that the protein SHBG increases with age and therefore, more T is bound and less is free. A third issue is the possible decline in the level of sensitivity of T receptors (especially those in the central nervous system) which might explain both reduced sexual desire in the aging male and the need for large doses of T in treating hypogonadal states in older men.
Segraves and Balon summarized results of the changes in T that accom- pany aging as follows (22):
Decreased: Production; the number of Leydig cells in the testis; the levels of bound and free hormone; testicular response to LH.
Increased: SHBG; estradiol; FSH; LH.
Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are androgens that originate in the adrenal glands. “To date, no carefully controlled study of dehy- droepiandrosterone’s effect on libido has been studied” despite observations on the benefits of DHEA on erections (22).
PRL derives from the anterior pituitary gland and its secretion is tonically inhibited by the hypothalamus through a balance of hypothalamic prolactin- inhibiting hormone (PIH) and putative prolactin-releasing hormone (PRH) (28). PIH is actually dopamine; so, anything that interferes with dopamine production results in increased PRL (the most common pathological reason being the use of many drugs used in psychiatry, e.g., risperidone and the phenothiazines).
Elevated PRL in men (and women) results in diminished sexual desire, as well as the possibility of erection and/or ejaculatory problems in the form of
diminished volume. In a very informative study of men presenting to a clinic because of sexual disorders and who were later found to be hyperprolactinemic, Schwartz et al. (29) concluded that it was generally futile to attempt to separate “psychogenic” and “organic” sexual problems, because many of the men pre- sented with a situational pattern that seemed to be exacerbated by psychological factors and that improved at times of increased arousal. Even more striking (and a sobering lesson to those who are not flexible in their approach to treating sexual problems in men), sex therapy administered before the hyperprolactinemia was discovered, actually resulted in improvement!
Theoretical Perspectives: Biological, Psychological, and Social
Not only are there multiple origins for HSDD in men, but the theoretical perspec- tive of the observer regarding sexual issues as a whole make understanding sexual problems like HSDD even more difficult.
One might look first at differing points of view about sexuality in general. Some view sexual difficulties from primarily a biomedical perspective and regard “sex” as “natural.” Kolodny et al. wrote: “to define sex as natural means just as an individual cannot be taught to sweat or how to digest food, a man cannot be taught to have an erection, nor can a woman be taught to lubricate vaginally. Because the reflex pathways of sexual functioning are inborn does not mean that they are immune from disruption due to impaired health, cultural condition- ing, or interpersonal stress” (30; p. 479) “Some have reworded ‘naturally’ to mean ‘automatically, without purpose or without effort’ ” (31).
Others look at sexuality and see the absence of intimacy as being crucial to understanding the psychological origins of many sexual difficulties (11,32). One can particularly appreciate (and learn from) the implications of the absence of intimacy for sexual relationships generally, and sexual desire in particular, when considering the plight of those with a serious mental illness who, by the very nature of the disorder, also have substantial intimacy difficulties (33). “The roots of intimacy difficulties are in the patient’s past … this … needs to be thoroughly explored because it may well have included turmoil in his or her family-of-origin, as well as a dearth of love and nurturing connections which are so often a rehearsal for love relationships later in life. Likewise, the patient’s past may not have included the experimental love and sexual relationships of adolescence in which so much learning takes place about oneself and others.”
Still others look at sexual matters from a “social constructionist” point of veiw. Tiefer wrote that “the primary influences on women’s sexuality are the norms of the culture, those internalized by women themselves and those enforced by institutions and enacted by significant others in women’s lives” (5; p. 2)
It may well be that these viewpoints do not apply equally to men and women, and that sexuality in men is, for example, more “natural.” However,
even as the word “natural” is applied to men, it does not explain the contribution to sexual problems of either intimacy issues or cultural variations in sexual behavior.
“During development and growth, there is interaction with the environment
that builds up experience and potentiation of ‘sexual’ stimuli. The social and cul- tural environment determines sexual expression and the meaning of sexual experience” (31).
See “Theoretical Perspectives” immediately above (11,32,33).
Little endocrine research has been done on men with HSDD.
Schiavi et al. compared 17 physically healthy men with HSDD to 17 age- matched non-dysfunctional volunteers (34). All were 25 – 55 years old. The HSDD men were described as having a generalized and persistent lack of sexual desire. Men with HSDD who did and did not have accompanying erectile problems, were also compared. The authors found that men with HSDD had sig- nificantly lower plasma total T levels (but not FT, PRL, LH, or estradiol) measured hourly throughout the night, when compared with controls. As well, they also reported that the men with secondary erectile problems had a different nocturnal penile tumescence (NPT) pattern than those whose erections were not problematic. The authors concluded that there was a relation between the decrease in T and the diminution in sexual drive and speculated that NPT findings may reflect a central biological abnormality. In support of the latter idea, they cited another study in which they found that men with HSDD had a higher preva- lence of mood disorders on a lifetime basis (but not at the time of evaluation) and wondered if both mood and sexual desire disorders might represent some neuro- biologic abnormality (35).
Presence of Another Sexual or Gender Disorder in a Patient or Partner
Three studies demonstrate that it is common for HSDD to be associated (or comorbid or correlated) with another sexual dysfunction. However, correlation is not the same as causation. The same factor(s) may result in both disorders. Nevertheless, the observation is at least noteworthy, and beyond that, may be etiologically meaningful.
1. Segraves and Segraves reported on 906 subjects (including 374 men) who had been recruited for a pharmaceutical company study of sexual disorders (20). Only the men will be discussed in this chapter. They were described as age 51 (SD ¼ 10.1), and 30% (n ¼ 113) had a primary diagnosis of HSDD. Almost half (47%) had a secondary diagnosis of erectile impairment and a few (n ¼ 3) had retarded ejaculation (patients with premature ejaculation were excluded from the study).
2. Schiavi reviewed 2500 charts of individuals and couples referred between 1974 and 1991. This survey included 1775 men, of which 13.3% (n ¼ 236) were 60 years old or older (range 60 – 84). Most of the men (66%) were diagnosed with erectile disorder but 28% had HSDD either alone [3% (n ¼ 8)] or associated with another sex- related diagnosis [ED—14% (n ¼ 34); PE—11% (n ¼ 27)]. In some, ED was the cause while in others it was the result. In most “it was not possible to determine the primary dysfunction” (36: p. 115).
3. Together with colleagues, Schiavi also examined the psychobiology of a group of sexually healthy men aged 45 – 74 living in stable sexual relationships (36; pp. 41 – 53). Seventy-seven couples were studied. One of the issues considered was a comparison of men with and without a sexual dysfunction. Seventeen men met their criteria for erectile dysfunction and five for HSDD (22% and 6.5%, respectively, of the total group). They found a significant difference in the age of the HSDD men who did and did not have accompanying ED (70.8 and 58.6 years, respectively). They added that the number of men with HSDD was too small to do any statistical comparisons with men who were not experiencing this disorder.
Sexual Difficulties in a Partner
Sexual difficulties in a partner, for example, intercourse-related pain experienced by a woman, may result in profound change in the level of sexual desire in the other person.
Rob and Melissa (not their real names), both 23 years old and university stu- dents, were referred because intercourse had not yet occurred in their 3- month-old marriage. With relish, they regularly engaged in other sexual activi- ties. History from both, plus her pelvic exam, revealed a diagnosis of vaginismus uncomplicated by vaginal pathology. Conventional treatment of vaginismus was successful in a technical sense (intercourse took place), but Melissa was cha- grined to find that it was not as pleasurable as she anticipated (12). From the time of Rob’s initial attempt to insert even part of his penis, he was concerned over her report of intercourse-related pain, and found that his sexual desire had diminished considerably when compared with the pre-treatment level. He found that in general, he was thinking much less about sexual matters, and when he and Melissa were sexual together, his erections were less than full and he was unable to ejaculate in her vagina. Moreover, he reported that his desire
to masturbate had plummeted. His sexual desire slowly returned (but not to the pre-treatment level) as he accepted her reassurance that her intercourse pain was progressively diminishing. Her continuing lack of physical pleasure in intercourse (she looked forward to the closeness) seemed to impede the recovery of his own desire.
Child Sexual Abuse (CSA)
The results of investigations on the sex-related impact of CSA on adult men are unclear. One study indicated that did not predict sexual dysfunction in a clinical sample of adult men asking for treatment of this disorder (37). However, in a different study that reviewed the sexual consequences of CSA on adolescents and adults, the authors described a wide variety of effects on adult men (although HSDD was not reported) (38).
Paraphilias (PAs) and Paraphilia-Related Disorders (PRDs)
PAs and their cousins, PRDs, usually manifest with a high level of sexual desire
(39). However, from the perspective of a partner, the opposite is usually the case.
Alan and Amy (not their real names), both 32 years old; were referred by their family physician because of Alan’s low level of sexual desire which had been a problem for most of the 7 years of their marriage. They lived alone. Alan was a university professor and Amy was a primary school teacher. Their first 6 months together (they had lived in separate cities before marrying) were sexually harmonious but difficulties became apparent after that time. They explained that nowadays they would go to bed at different times, and that he would hardly touch her. Six months prior to the first visit, she discovered magazines in the back of his car which depicted men dressed as women. Alan asked Amy if he could do the same when they were sexual together, that is, be dressed as a woman. She tried on a few occasions but eventually found the idea to be repellant.
When Alan was seen alone, he explained that his low level of sexual interest was only in relation to his wife but that whenever possible, he would get dressed as a woman, found himself sexually aroused in the process, and masturbate. They were referred for care to a psychiatrist who specialized in treating couples where one partner had a paraphilia.
Medical conditions in which all sexual dysfunctions occur, and more specifically loss of sexual desire, result from biological, psychological and/or social, or inter- personal factors, and most often from a combination of these elements (40). Examples of biological factors include: direct physiological effects of the
illness or its treatment, physical debilitation, and bowel and/or bladder inconti- nence. Examples of psychological factors include: adopting the “patient role” as an asexual person, altered body image, mood difficulties, and fear of death or rejection by a partner. Examples of social and interpersonal factors include: com- munication difficulties regarding feelings or sexuality, difficulties initiating a sexual encounter after a period of abstinence, lack of partner, and lack of privacy.
Cardiovascular Diseases (22)
These include disorders of the heart (myocardial infarction, angina pectoris, cor- onary artery disease, conduction problems), hypertension, and atherosclerosis. Cardiac problems may cause sexual difficulties on their own or as a result of their treatment (see later). Likewise, just experiencing the disorder may cause mood or body image problems. Some cardiovascular diseases may result in avoidance of sexual activity and therefore its limitation. Whenever a sexual dys- function occurs in the context of a cardiovascular disease, the clinician should attempt to separate the various etiological factors.
The “general comments” made earlier are particularly applicable in any discus- sion of cancer.
Of all types of epilepsy, that which affects the temporal lobe (TLE) has been the most frequently studied in relation to sexual consequences. TLE is particularly linked with low sexual desire in patients undergoing temporal lobe surgery (an admittedly unrepresentative group afflicted with this disorder) (41). The associ- ation between other kinds of epilepsy and low sexual desire is unclear.
Kleinfelter’s syndrome (47 XXY).
Trauma; mumps orchitis, undescended testes.
Secondary Hypogonadism (Resulting from
Pituitary tumors (especially prolactinoma); and iron overload disorders (e.g., hemochromatosis and thalassemia).
Cushing’s syndrome, diabetes.
Chronic renal failure, chronic liver disease, AIDS.
Sexuality is commonly affected by mood disorders. Specifically, diminished sexual desire is often seen as a feature of depression (42). Schreiner-Engel and Schiavi looked at the relationship between HSDD and depression using an uncon- ventional strategy (35). They examined couples where one partner reported gen- eralized HSDD (22 of the men and 24 of the women—all of whom were euthymic at the time) and compared them to a control group. Interestingly, they found that those with sexual desire difficulties had a significantly higher lifetime rate of affective disorder—almost twice as high as the control group. Furthermore, the authors theorized that there may be a common biological etiology to the two dis- orders, or, that affective psychopathology may contribute to the pathogenesis of the desire disorder.
There is little information on sexual dysfunctions in untreated euthymic patients who have a bipolar disorder. However, manic patients are often described as “hypersexual” but the meaning is often not clear. “Hypersexual” could refer either to either an increase in sexual desire, or an increase in sexual activity (which may result from factors other than sexual desire such as having an exag- gerated opinion of one’s desirability).
Finding an untreated population of people with this disorder is unusual as is any attempt to establish the nature of sexual desire in this condition that is separate from medications.
In a study of sexual dysfunctions and posttraumatic stress disorder (PTSD) in men, three groups were compared: (i) untreated patients (n ¼ 15), (ii) PTSD patients treated with selective serotonin reuptake inhibitors (SSRIs) (n ¼ 27), and (iii) normal controls (43). Untreated and treated PTSD patients had signifi- cantly poorer sexual functioning in all domains examined, including sexual desire.
Unfortunately, few double-blind placebo-controlled trials exist to guide clini- cians in understanding the sexual impact of medications. As a result, much of the information that follows is based on less refined information as, for example, case reports. Caution in interpretation is therefore advisable.
Unless otherwise referenced, information in this section has been taken from Segraves and Balon (22) and Kaufman and Vermeulen (23).
In general, there is often great difficulty in differentiating the sexual conse- quences of a disorder from side effects of the medication used in treatment. When thinking about a sexual desire problem, attempting this separation requires care in determining that it did not exist before drug treatment began (i.e., making sure that it is, in fact, acquired rather than lifelong). Likewise, one would expect drug-related sexual problems to occur under all circumstances rather than some (i.e., to be generalized rather than situational), and that the desire problem would disappear if the drug is stopped but reappear if resumed. Last, one would want to determine that the diminished sexual desire would not be better explained by the onset of an illness or exposure to an environmental stress.
This group includes those which are “typical” (also called “neuroleptics” and “traditional,” for example, phenothiazines, thioxanthenes, and butyrophenones), as well as “atypical” (e.g., risperidone, olanzapine, quetiapine, and clozapine). Men who are taking antipsychotic drugs generally complain of various sexual side effects including loss of sexual desire (although interference with ejaculation seems particularly common). One factor that seems especially noteworthy is that many of the typical antipsychotics, as well as risperidone in the atypical group, result in an elevation in PRL which, in turn, has significant sexual consequences including a lessening of sexual desire (see below).
Alprazolam (Xanax) was reported to sometimes result in diminished sexual desire in both men and women (44). In that SSRIs are often used to treat anxiety, the information on “antidepressants” immediately below is of relevance.
The incidence of sexual dysfunction generally with antidepressants is estimated at 30 – 50%. All types of antidepressants (TCAs, MAOIs, SSRIs) are linked to decreased sexual desire. Sexual dysfunctions generally are said to be less with bupropion, mirtazapine, moclobemide, and maybe reboxetine.
Lithium may result in diminished sexual desire in a minority of patients.
Drugs Used in Urological Practice
Finasteride is used in the treatment of benign prostatic hypertrophy (BPH); its mode of action is to block the conversion of T to DHT by inhibiting the enzyme 5-alpha reductase. Diminished sexual desire is commonly reported.
Several drugs are used in the treatment of prostate cancer, a disease which is often androgen-dependent. The treatment strategy is therefore to lower or
eliminate the effect of androgens which, in turn, has a predictable markedly nega- tive impact on sexual desire. Flutamide interferes with the binding of T and DHT to the androgen receptor. Flutamide is used both alone and in combination with either leutinizing-hormone releasing hormone (LHRH) or finasteride. Drugs used to treat metastatic prostate cancer include LHRH agonists (synthetic analogues of LHRH including leuprolide, flutamide, nafarelin, and nilutamide), and androgen receptor blockers. LHRH agonists act by blocking the pituitary release of gonadotropins thereby decreasing the production of androgens (Fig. 4.3).
Substances that are known to be associated with lowering of sexual desire include: chlorthalidone, clofibrate, clonidine, gemfibrozil, hydrochlorthiazide, methyldopa, propanolol, reserpine, spironolactone, and timolol.
Cancer Chemotherapy Drugs
Cytotoxic drugs often have substantial effects on the gonads. Loss of sexual desire often accompanies their use and may be, at least in part, a result of hormo- nal changes. The treatment of some cancers in men might involve the use of anti- androgenic drugs resulting in a substantial decrease in T. Bone marrow transplant (BMT) in men may cause a substantially lower level of sexual desire. Androgen replacement therapy is often suggested to men who have received high-dose chemotherapy with BMT.
Carbamazepine, clonazepam, gabapentin, phenobarbital, phenytoin, and primi- done have been linked to sexual dysfunction (including, but not limited to, low sexual desire). The picture is often confounded by the appearance of sexual disorders associated with epilepsy itself as well as with the paucity of published information on this entire subject. Sexual effects seem related to enzyme induc- tion as well as changes in sex hormone levels (via SHBG), and possibly, neurotransmitters.
Recreational drugs include nicotine, marijuana, alcohol, heroin, methadone, and MDMA. Given the connection between cigarette smoking and ED as well as the apparent link between ED and HSDD, nicotine can be considered as an indirect cause of sexual desire disorders in men. Many who use marijuana frequently also report low sexual desire. The sexual effects of chronic use of alcohol are legion and include ED (possibly due to peripheral neuropathy), testicular atrophy, low T, and high SHBH in those with cirrhosis, and hyperestrogenism also associated with alcohol-related liver disease. Any of these difficulties may also result in low sexual desire. Chronic use of heroin and all other opiates results in diminished sexual desire, possibly related to low T levels.
Drugs Used in Gastrointestinal Practice
Cimetidine has been reported to result in diminished libido in men and to have an antiandrogenic effect.
Freud described a man choosing one woman for love and another for sexual activity and seemingly unable to fuse the two (45). He referred to this idea as the Madonna/Prostitute Syndrome. This notion seems especially applicable today to some young men who also relate experiences consistent with a lifelong and situational form of HSDD (12; and see Case Study in the “Lifelong and Situational” section of the “Classification” section).
Severe medical and psychiatric illness can alter partner-related sexual desire.
Tanya and Phillip (not their real names) were each 27 years old and married for the first time for 3 years. They did not have children, did not smoke or use street drugs, and neither had had major health problems in the past. They described themselves as Christian and although they did not have intercourse before marriage, they “could not keep their hands off each other” during that time and enthusiastically engaged in a variety of sexual activities. Their sexual experiences in the early years of their marriage were uncomplicated and highly pleasurable to both. In the second year of their marriage Tanya developed an episode of mania. When they were initially referred (because of lack of sexual desire on Phillip’s part), she had been taking maintenance medication for the previous 12 months.
When Phillip was seen alone (they were initially seen together), he pro- fessed his continuing love for Tanya but at the same time said that she was not the same person whom he married. He hoped that their active and pleasurable sexual experiences would return and was puzzled by his own diminished sexual desire. He found himself thinking about sexual matters and fantasizing about old girlfriends. He had masturbated regularly before he and Tanya met but not through their courtship and early part of their marriage. He had begun mastur- bating again in recent months and contrary to his expectations, the frequency had not diminished. He had no idea why his sexual desire for Tanya had seemingly disappeared.
Although little exists in the literature on the sexual impact on partners when one of them becomes ill, the syndrome of diminished sexual interest in the well partner is familiar to sexuality professionals who work with the physically ill in rehabilitation centers (B. Lawrie, personal communication, 2004). The change seems much more evident in men than women, perhaps because men are
generally perceived as perpetually sexually interested and ready in a way that is ordinarily unaffected by environmental circumstances. The very fact that men are so influenced by severe illness in a partner suggests that this general perception is exaggerated. In the context of Levine’s tripartite definition of sexual desire, men in this instance lose the “motive” to engage in sexual activity with their partner (even though the drive may continue to exist) (2).
From both the point of view of clinical impression as well as clinical research, anger resulting from relationship discord seems to have a different effect on sexual desire in men compared with women. An experimental study may bear this out. Twenty-four men and an equal number of women, all university stu- dents, were asked to indicate their level of sexual desire in relation to audiotapes describing different sexual events (46). When subjects were presented with a stimulus that provoked anger, the authors found that significantly fewer men (21%) than women (79%), indicated that they would have terminated the sexual encounter.
Examples of psychosocial issues include: religious orthodoxy, anhedonic or obsessive-compulsive personality traits (accompanied by difficulties displaying emotion as well as discomfort with close body contact), widower’s syndrome (found in a man after his partner has died and resulting from attachment to his partner or the unfamiliarity of sexual activity with a new person), lack of attrac- tion to partner, and primary sexual interest in other men (47).