Drug-Induced Sexual Dysfunction

Sexual dysfunction tends to be under reported since patients are often reluctant to discuss sexual health-related issues. Fortunately, as sexual health becomes less of a taboo subject, recognition that it is integral to one’s overall well-being, and that drug therapy can adversely affect it, is becoming more widespread.

While not life-threatening as such, sexual dysfunction can afect one’s personal relationships and ability to conceive. And since it has been shown that patients with depression, schizophrenia and hypertension often discontinue taking their medication due to sex-related side effects, sexual dysfunction is also a factor in prescription non-compliance.

Factors that can affect sexual function include age, smoking, drugs and alcohol abuse, over-the-counter medicines, prescription drugs, and exposure to environmental toxins. Many diseases can also affect sexual function, so direct causality with a drug is difficult to establish. It is even more difficult to do so with female patients since most published literature on the adverse effects of drugs on sexual function deals with males. There is a wide range of drugs, however, that is known to affect the sexual function of patients regardless of their sex, notably antidepressants, antipsychotics, and antihypertensives.

Sexual dysfunctions can be generally categorized as those relating to:

• Lack of libido or sexual desire – libido is affected by reproductive hormones and physical and emotional health.
• Arousal problems (reduced vaginal lubrication in women, erectile dysfunction in men)
• Release (failure to achieve orgasm in women, ejaculation in men)
• Priapism, a prolonged penile erection usually unrelated to sexual stimulation

Generally, dopamine tends to increase sexual behavior, serotonin tends to inhibit it, and testosterone is necessary for normal sexual arousal in both men and women. Testosterone deficiency in men is associated with impotence.

Erectile dysfunction (ED) is the most common form of male sexual dysfunction. Its prevalence is up to ten percent across all ages and increases to over 50 percent in men 50 to 70 years of age. Causes include vascular factors, endocrine disease, neurological dysfunction and drug therapy. It often occurs in those with heart disease, hypertension,diabetes and peripheral vascular disease. Ejaculatory disorders are comprised of ejaculatory failure and retrograde ejaculation (in which semen passes into the bladder). Approximately 25 percent of cases are estimated to be drug-induced.

In women, the most commonly reported form of sexual dysfunction is loss of libido. But women are rarely questioned about how medication affects their sexual function, so case reports tend to be anecdotal. Drugs that have been implicated in affecting the sexual function of either or both sexes include:

• Antihypertensives – while it was thought that all antihypertensive drugs increase the incidence of ejaculatory disorders and erectile dysfunction, recent studies suggest that this depends on the class of such drug used. The importance of selecting the appropriate drug to treat hypertension is highlighted by additional evidence that suggests that patients who experience sexual side effects will discontinue taking their medication.
• Anti-androgens – these are used to treat excessive sexual desire, sexual deviation, prostate cancer, prostate enlargement, certain types of acne, male pattern baldness, excessive hairiness and as a male contraceptive. They include drugs such as finasteride (Propecia, Proscar), spironolactone (Spiritone, Aldactone), cyproterone acetate (Androcur, Diane 35, Climen, Ginette 35), flutamide (Eulexin), nilutamide (Nilandron, Anandron), bicalutamide (Casodex), and ketoconazole (Nizoral), and have a potential for causing ED, decreased libido, decreased volume of ejaculation, impotence, and breast tenderness or enlargement, among other side effects. Alpha-adrenergic blockers such as prazosin and indoramin can also cause retrograde ejaculation. Guanethidine and reserpine, which are no longer used, are associated with high rates of erectile dysfunction and ejaculatory failure.
• Adrenegic agents – primarily used to treat hypertension. Methyldopa and clonidine have been known to cause loss of libido in both men and women, erectile dysfunction, ejaculatory failure and anorgasmia in women.
• Beta-blockers – these are a class of adrenegic agent. ED is well documented with propranolol (Inderal, Avlocardyl, Dociton, Inderalici, Sumial) and has been reported with atenolol (Tenormin) and ophthalmic timolol (Timoptic, Timoptol), although it can occur with other beta-blockers, especially those that are lipid soluble.
• Thiazide diuretics – are also used to teat hypertension and may cause decreased libido, ED, and problems with ejaculation.
• Other diuretics – the incidence of sexual dysfunction seems to be greater for men taking diuretics in general. Spironolactone (Aldactone, Berlactone , Novo-Spiroton, Spirotone, Spiractin, Verospiron), a potassium-sparing diuretic, has been associated with impotence, breast enlargement in men, decreased libido in both men and women, and menstrual irregularities.
• Calcium channel blockers – used for hypertension and epilepsy. Although there are some case reports of ED from the use of these drugs, they seem to cause fewer difficulties with sexual function than beta-blockers or diuretics.
• Psychotropic drugs (selective serotonin reuptake inhibitors [SSRIs], tricyclics [TCAs], monoamine oxidase inhibitors [MAOIs]) – both antidepressant and antipsychotic drugs adversely affect sexual function in men and women to some degree. While not definitively established, several case reports have implicated TCAs in ED. Trazodone has been known to increase sex drive in both men and women. There are also case reports of spontaneous orgasm in women induced by clomipramine when yawning. Serotonergic antidepressants such as SSRIs, MAOIs and clomipramine are associated with high rates of ejaculatory disturbance, delayed orgasm, anorgasmia (inability to reach orgasm), and decreased libido. With SSRIs, decreased libido is possibly due to its indirect effect on dopamine levels. SSRIs, in fact, are sometimes used to treat premature ejaculation. Olanzapine and other newer antipsychotics may be less likely to cause ejaculatory problems. Delayed orgasm and anorgasmia have  been reported by women treated with clozapine and risperidone, and spontaneous, in some cases multiple, orgasms have been reported by women treated with fluoxetine (Prozac).
• Omeprazole (Losec, Prilosec, Zegerid, Omez) – a proton pump inhibitor that is used to treat dyspepsia (indigestion), peptic ulcer disease (PUD) (erosion in the lining of the stomach or duodenum), gastroesophageal reflux disease (GERD/GORD) and Zollinger-Ellison syndrome (tumors in the pancreas that produce large amounts of a hormone that leads to excess acid and a possible ulcer of the stomach or upper part of the small intestine). There are some reports of users experiencing ED.
• Anxiolytics – there are case reports of decreased libido, probably due to its centrally-mediated sedation and muscle relaxation.
• Protase inhibitors – used to prevent viral infections such as HIV and Hepatitis C, preliminary data links protease inhibitors with loss of libido, ED and problems with ejaculation.
• Others – see following table:

Drug	Trade names include	What used for	Possible sexual dysfunction
Anticholinergics	Hyoscine, Hyoscyamine, Benadryl, Dramamine, Dicyclomine, Spiriva, Detrusitol, Vesicare, Enablex, Cogentin, Inversine	Numerous, including gastrointestinal disorders, Parkinson’s, asthma, COPD…	Decreased libido, delayed ejaculation, anorgasmia
Benzodiazepines: alprazolam, chlordiazepoxide, diazepam, lorazepam, triazolam, etc.	Xanax, Librium, Valium, Ativan, Halcion, etc.	Anxiety, agitation, insomnia, seizures, muscle spasms, alcohol/drug withdrawal	Decreased libido. Delayed orgasm or anorgasmia in women
Carbamazepine (CBZ)	Tegretol, Biston, Carbatrol, Calepsin, Equetro, Epitol, Finlepsin, Stazepine, Sirtal, Telesmin, Teril, Trimonil, Timonil, Epimaz, Degranol	Epilepsy	ED
Cimetidine	Tagamet	Peptic ulcers, acid reflux disease	ED, loss of libido
Digoxin	Lanoxin, Digitek, Lanoxicaps	Atrial fibrillation, atrial flutter, heart failure	Decreased libido, ED
Estrogen	TACE, Cenestin, Premarin, DV, Ortho Dienestrol, Diethylstilbestrol, Estratab, Menest Tablets, Estrace, Estraderm, Ogen, Ortho-Est, Estinyl, Feminone Tablets, Estrovis	Menopause symptoms, osteoporosis, ovarian failure, breast cancer, advanced cancer of the prostate, abnormal bleeding of the uterus, vaginal irritation, birth control, female castration, Tumers syndrome	Changes in menstruation, increased sex drive in women, decreased sex drive in men
Gonadorelin analogues	De-capeptyl, Prostap, Suprecur, Synarel, Zoladex	Endometriosis, precocious puberty, uterine leiomyoma,  prostate and breast cancers	Decreased libido, vaginal dryness
Metoclopramide	Maxolon, Reglan, Degan, Maxeran, Primperan, Pylomid	Nausea and vomiting	Decreased libido, ED
Phenothiazines: chlorpromazine, thioridazine, promazine, triflupromazine, methotrimeprazine, mesoridazine, fluphenazine, perphenazine, flupentixol, prochlorperazine, trifluoperazine	Thorazine, Sparine, Stelazine, Nozinan, Serentil, Mellaril, Prolixin, Trilafon, Depixol, Compazine	Psychotic illness	Decreased libido, ED, ejaculatory disturbances (Thioridazine has been reported to  cause inhibition of female orgasm)
Phenytoin	Phenytek, Dilantin,  Kapseals, Dilantin, Infatabs, Eptoin, Epanutin	Epilepsy, trigeminal neuralgia, cardiac arrhythmia	ED
Levodopa	Symmetrel	Parkinson’s disease	Hypersexuality in men

Priapism, a prolonged penile erection usually unrelated to sexual stimulation occurs when venous drainage from the corpora cavernosa (spongy vascular tissue that makes up most of the penis) is obstructed. This can happen when the regulatory mechanisms that initiate and maintain flaccidity of the penis are disturbed. If the condition is not treated promptly, it can lead to permanent scarring, inability to have a normal erection, and even gangrene.

Up to 40 percent of priapism cases are drug induced. Prazosin (Minipress, Hypovase) and other alpha-androreceptor antagonists used to treat hypertension are most frequently associated with priapism. Phenothiazines and trazodone are the most commonly implicated psychotropic drugs. Papaverine, alprostadil, phentolamine and similar drugs administered by intracavernosal injection to treat ED may also cause priapism and patients should be warned beforehand. Other drugs that may cause priapism include nifedipine, hydralazine, risperidone, haloperidol, hydralazine and anticoagulants.

Management and treatment of drug-induced sexual dysfunction may range from dose reduction, to changing drug therapy, to the prescription of an additional drug that directly treats the underlying physical cause, although this last option is rarely indicated. In some cases, there may not be an effective or acceptable alternative. In others, the problem may remit spontaneously.

Sexual dysfunction involves sensitive and complex issues. If you suspect that a sexual problem may be drug related, it is usually advisable to consult with your general practitioner.