46: Sexual Health & Dysfunction

Although older men and women are still interested in sex, sexual activity declines with age. In the Massachusetts Male Aging Study, more than 60% of men age 70 years reported erectile dysfunction and in the Rancho Bernardo Study, 32% of women age 65 years or older reported sexual activity in the previous 4 weeks but only 13% of women age 80 years or older reported being sexually active. This decrease in sexual activity may negatively impact quality of life. Fortunately, there are effective treatments for sexual dysfunction in men and women.

In men, age-related physiologic changes impact sexual function. Alterations in the pituitary–hypothalamic–gonadal axis may result in hypogonadism and decreased libido. Changes in penile innervation make it more difficult to achieve an erection, increase the time it takes to have an orgasm, and prolong the refractory period (the time it takes to have an erection after ejaculation). The increased time to ejaculate may actually improve sexual function in men who are premature ejaculators.

In women, the 4 phases of sexual response (excitement, plateau, orgasm, and resolution) change with aging. During the excitement phase, there is decreased genital engorgement. Vaginal lubrication is decreased and the woman may need longer foreplay and gentle stimulation to achieve sufficient lubrication for intercourse. During the plateau phase, there is less expansion and vasocongestion of the vagina. During orgasm, there are fewer and weaker contractions, although older women can still achieve multiple orgasms. During the resolution phase, vasocongestion is lost more rapidly. As in younger women, the 4 phases may vary in sequence, overlap, or some may be absent. For example, desire does not always precede arousal. An older woman may engage in sexual activity not out of desire for sex but out of desire for closeness with her partner. If the stimulation is appropriate and she stays focused, her arousal and sexual desire intensifies. A positive experience increases her motivation for future encounters whereas a negative one (eg, from dyspareunia) may decrease her interest in sex.

In addition to the physiologic changes that occur with aging, lifestyle choices, psychological factors, and aging-related diseases and their treatment may affect sexual function in both men and women.

Men

The most common cause of sexual dysfunction in older men is erectile dysfunction (ED). The National Institutes of Health (NIH) defines ED as the consistent inability to achieve and/or maintain an erection sufficient for satisfactory sexual activity. As noted above, more than 60% of men age 70 years are unable to achieve a rigid erection. ED is the most common chronic disease in men, and vascular disease is the most common cause of ED.

Risk factors for vascular disease include lack of exercise, diabetes mellitus, hyperlipidemia, hypertension, and smoking. In many cases, these diseases are preventable by dietary and lifestyle changes. Because of the correlation between ED and vascular disease, ED is a marker for future vascular events, such as myocardial infarction and stroke. However, ED may be a more powerful predictor of cardiovascular disease in men younger than 60 years of age and in patients with diabetes.

Diabetes mellitus (DM) has the greatest impact on sexual function in men. The risk of ED in DM is directly related to the duration of diabetes, the A1c level, and increasing age. Early aggressive control of DM may prevent ED or delay its onset.

The second most common causes of ED are neurogenic. The autonomic dysfunction seen in DM and Parkinson disease prevents penile vasodilatation and erection. DM may cause both vascular and neurogenic ED. Neurogenic ED is frequently seen after prostatectomy or radiation therapy for prostate cancer. Nerve sparing surgery reduces this risk.

Another common cause of ED is medications. Anticholinergics, such as antipsychotics and oxybutynin, block parasympathetic-mediated vasodilatation. Antihypertensives, including beta blockers and thiazides, also increase the risk of ED. Angiotensin-converting enzyme inhibitors and calcium channel blockers do not have an adverse impact on erections.

Psychogenic ED is the least-common etiology. Patients with psychogenic ED usually describe the sudden onset of ED related to an event in their lives (argument with their partner, losing a job, etc). Of note, patients with ED caused by a nonpsychogenic etiology may have anxiety and/or depression because of the ED.

Testosterone’s role in ED is controversial. Low testosterone is associated with decreased libido, but hypogonadal men can still achieve an erection and most men with ED have normal testosterone levels. Studies in animals suggest that testosterone is needed for a rigid erection. Studies also show that testosterone replacement in hypogonadal men improves their response to phosphodiesterase type 5 inhibitors.

Premature ejaculation (PE) occurs in approximately 30% of men. These patients are also referred to as “rapid ejaculators.” PE is defined as orgasm with minimal stimulation. The most common cause is neurophysiologic. PE may also be psychogenic. Most PE is chronic. Patients with acute onset of PE may have a prostate infection (prostatitis). As men age, PE becomes less of a problem because of changes in penile innervation resulting in decreased penile sensation.

Retrograde ejaculation is a common complaint in men who have DM or have undergone transurethral prostatic resection. In both cases, the proximal sphincter does not close during ejaculation and semen goes into the bladder.

Orgasmic failure is uncommon in men. When it does occur, it may be a result of nerve damage (prostate cancer, radical prostatectomy, or DM) or may be medication-induced (gabapentin). With the exception of stopping gabapentin, treatment is usually unsuccessful.

Women

A decrease in estrogen levels with menopause can have a negative effect on sexuality by causing vaginal dryness. The normal vaginal pH is 3.5–4.5; after menopause it increases up to 7.0–7.39. A pH higher than 5 increases the risk of urogenital atrophy and bladder infections.

Women with poor self-reported physical health and women with diabetes are less likely to be sexually active than healthy older women.

These sexual difficulties constitute a “dysfunction” only if they cause significant distress to the woman, so if lack of interest in sex does not bother the woman, she cannot be diagnosed as having sexual dysfunction. Female sexual dysfunction is classified depending on whether the main problem is in one of these 4 areas: arousal, orgasm, desire, or pain.

Like in men, libido in women is thought to be dependent on testosterone. Estrogen replacement can improve vulvovaginal atrophy symptoms, but it has little effect on libido or sexual satisfaction. The ovaries and adrenals are the main sources of androgens in women. The effects of lack of testosterone in women were originally identified in women treated for advanced breast cancer with oophorectomy and adrenalectomy. When deprived of androgens, these women reported loss of libido. As there are no normative data on plasma total and free testosterone in women and there is no well-defined clinical syndrome of androgen deficiency, the Endocrine Society does not recommend making a diagnosis of androgen deficiency in women.

In older women, the etiology of sexual dysfunction depends on whether the patient presents with decreased desire, decreased lubrication, delayed or absent orgasm, or pain with intercourse (Table 46–1), but often the cause is multifactorial. For example, the patient may have decreased desire because of poor health and medication side effects and at the same time have painful intercourse.

Painful intercourse or “dyspareunia” can be caused by psychological or organic factors or a combination thereof. The most common cause of dyspareunia is vaginal atrophy caused by postmenopausal estrogen deficiency. The fear of experiencing pain may perpetuate the dyspareunia as it limits the woman’s ability to become aroused and have adequate lubrication. Other causes of dyspareunia include lack of lubrication, vaginismus, localized vaginal infections, cystitis, Bartholin cyst, or even poor male technique. Pain can occur from pelvic thrusting and can be attributable to the woman’s position during intercourse, retroverted uterus, postoperative adhesions, pelvic tumors, endometriosis, pelvic inflammatory disease, ovarian cysts, or urinary tract infections.

Symptoms & Signs

Men—

The evaluation of sexual dysfunction in men includes taking a good sexual history, physical exam, and a few lab tests. Patients may be reluctant to talk about their sexual function and the International Index of Erectile Dysfunction (IIEF-5) can be used to start this discussion. The IIEF-5 is self-administered and consists of 5 questions about sexual function during the past month. The IIEF-5 can be given to male patients to complete before the visit.

Obtaining a thorough history is the most important part of the evaluation of sexual dysfunction. The first step is to determine the specific nature of the problem. Does the patient have decreased libido, difficulty obtaining and/or maintaining an erection, PE, retrograde ejaculation, or anorgasmia?

The patient should be then asked about the onset (gradual vs. sudden) of the problem, the presence or absence of sleep-associated erections, and about any treatments that he has tried (both prescription and nonprescription). In men with ED, the onset and presence or absence of sleep-associated erections (SAEs) can help distinguish between psychogenic, medication-induced, and organic ED. Patients with psychogenic ED will describe a sudden onset but will still have SAEs. Men with medication-induced ED will also report a sudden onset, but will deny having SAEs. Finally, patients with organic ED will have a gradual onset and absent SAEs.

The physical exam targets signs of hypogonadism, vascular, and neurologic disease. Signs of hypogonadism include gynecomastia, decreased body hair, scant pubic hair or a female escutcheon. The vascular exam involves checking for bruits and palpating pedal pulses. The neurologic exam includes rectal sphincter tone, bulbocavernosus reflex and deep tendon reflexes. During the rectal exam the prostate should be checked for nodules. Finally, the penis should be examined for plaques (Peyronie’s disease).

Women—

As for men, the most important part of the evaluation is a careful history but the older woman might be reluctant to talk about her sexual function. There are several self-reported and interview-based screening tools, a simple screen comprises just 3 questions:

1. Are you sexually active?

2. Are there any problems?

3. Do you have pain with intercourse?

If the woman is not satisfied with her sexual life, further questioning is necessary to understand whether the problem is mainly with arousal, desire, orgasm, or pain or a combination of these areas. The woman should be asked about duration and consistency of the problem, quality of relationship and sexual communication between the couple, thoughts during sexual activity, amount and adequacy of vaginal lubrication, symptoms of depression and history of negative experiences, like rape, child abuse, or domestic violence.

The medical history is important as several chronic illnesses can cause sexual dysfunction: diabetes and other conditions that cause debility and poor function like rheumatic diseases, conditions that cause poor self-image like mastectomy, the presence of stoma, advanced pelvic organ prolapse, or incontinence. In 1 study, 22% of women with urinary incontinence feared that intercourse would cause urine loss.

The clinician should elicit a complete drug history as several drugs can contribute to sexual dysfunction, including selective serotonin-reuptake inhibitors, antipsychotics, antihypertensives, antiestrogens, antiandrogens, alcohol, and illicit/recreational drugs. Chronic use of opioids can affect sexual function by causing opioid-induced androgen deficiency. Anticholinergic drugs decrease normal vaginal lubrication.

In the older woman, the physical exam is directed by symptoms elicited during the history and is particularly important in older women who have not received regular medical care. A pelvic examination should be done if the patient complains of vaginal dryness and/or dyspareunia. The exam should also include blood pressure and peripheral pulses as vascular disease affects arousal, a musculoskeletal exam as rheumatologic disorders can cause pain and difficulty with sexual activity, thyroid exam as hypothyroidism can cause decreased desire or arousal, and screening for neuropathy as neurological disorders can cause decreased desire, arousal or anorgasmy.

Laboratory Findings

Men—

The laboratory evaluation of men with sexual dysfunction should include a hemoglobin A1c, a lipid panel and total testosterone. Because of its diurnal secretory pattern, testosterone should be obtained between 8 AM and 10 AM. If the testosterone is low, it should be repeated and luteinizing hormone (LH) level obtained. If the testosterone is low and the LH is high, the problem is at the level of the testes. If the testosterone is low and LH is low or normal, the patient has a hypothalamic or pituitary disorder and will need further testing.

Women—

Routine laboratory testing is not necessary to evaluate female sexual dysfunction. Testosterone levels do not correlate with sexual function. Prolactin and thyroid-stimulating hormone levels should be done only if the history or physical exam suggest possible abnormalities.

Men—

The choice of treatment in men depends on the etiology of the sexual dysfunction. In men with psychogenic ED, discussion and reassurance are frequently effective. If the patient continues to have ED, referral to a sex therapist may be necessary.

In men with decreased libido who are hypogonadal, testosterone replacement therapy may improve their sex drive. Contraindications to testosterone treatment include a history of prostate or breast cancer, polycythemia, severe lower urinary tract symptoms, or obstructive sleep apnea.

Neurophysiologic PE is treated with medications that delay ejaculation. These include the serotonin reuptake inhibitors, alpha blockers, and topical anesthetics. If a patient has prostatitis, an antibiotic usually cures the PE. In men with psychogenic PE, psychotherapy may help.

Retrograde ejaculation is a benign condition. Reassurance is the main treatment. The patient should be reminded that even without visible ejaculate, impregnation is still possible (if his partner is fertile).

The most common cause of sexual dysfunction in men is ED. However, before treating ED clinicians need to determine if it is safe for the patient to engage in sexual intercourse. The person on top during intercourse expends the equivalent of the energy needed to climb 2 flights of stairs. If a patient is sedentary and has cardiac risk factors (hypertension, DM, hyperlipidemia, or tobacco use) and/or known cardiovascular disease, a cardiac evaluation including a stress test may be needed before starting treatment for ED.

In patients with drug-induced ED, if possible the offending drug should be discontinued or changed to another agent/different drug class. For example, replace a beta-blocker with an erection-sparing agent, such as a calcium channel blocker. Of note, patients with drug-induced ED frequently have underlying vascular disease, now unmasked by the drug. If the ED is longstanding, patients may not see improvement in their erectile function with the change in agents.

However, in the majority of cases, ED is caused by vascular and/or neurologic disease. The only Food and Drug Administration (FDA)-approved treatments for ED are vacuum devices, phosphodiesterase type 5 inhibitors, intraurethral suppositories, and intracavernosal injection of a vasodilator (Table 46–2).

Vacuum constrictive device—

The vacuum constrictive device (VCD) was patented in 1917! It works by having the patient insert his penis in a plastic tube that is connected to a pump. He then pumps the air out of the tube and the resultant vacuum pulls blood into the penis and makes it erect. A rubber ring is slipped off the tube onto the base of the penis. The ring traps the blood in the penis and thereby maintains the erection. Patients or their partners may be reluctant to try VCDs because they are mechanical and take the spontaneity out of sex. However, VCDs are successful in 70% to 80% of patients who try them. Men should be warned not to leave the ring on for more than 30 minutes because the rings act like a tourniquet. VCDs with a battery powered pump are available for patients who have arthritis or another condition that limits their ability to use a manual pump.

Phosphodiesterase type 5 inhibitors—

When a man becomes aroused, there is stimulation of the penile nerve that results in the activation of nitric oxide synthase. Nitric oxide synthase catalyzes the production of nitric oxide from L-arginine. Nitric oxide diffuses into penile smooth muscle cells and activates guanyl cyclase which produces cyclic guanosine monophosphate (cGMP). cGMP relaxes smooth muscle resulting in vasodilatation and erection. cGMP is metabolized by phosphodiesterase type 5 (PDE5). PDE5 inhibitors prevent the breakdown of cGMP thereby increasing vasodilation and erection.

There are 4 FDA-approved PDE5 inhibitors in the United States: avanafil (Stendra®), sildenafil (Viagra®), tadalafil (Cialis®), and vardenafil (Levitra®). Avanafil, sildenafil and vardenafil are taken “on demand.” Tadalafil has both “on demand” and daily dosing. With the exception of the daily tadalafil, these medications are taken at least 30 minutes before initiation of sexual activity. The starting doses are 100 mg for avanafil, 25 mg for sildenafil, 10 mg for tadalafil, and 5 mg for vardenafil. The starting daily dose of tadalafil is 2.5 mg.

Side effects are usually mild and related to smooth muscle relaxation. They include headache, flushing, esophageal reflux and rhinitis. Sildenafil may cause “blue haze,” a transient disturbance in color vision, because of its effect on retinal PDE6. Tadalafil may cause muscle aches and back pain from its effect on PDE11. Vision loss, from nonarteritic anterior ischemic optic neuropathy, and sudden hearing loss have been reported in a small number of men taking PDE5 inhibitors. The relationship between these events and PDE5 inhibitors is unclear. However, patients should be warned to stop taking PDE5 inhibitors and seek immediate medical attention for sudden decreases or loss of vision or hearing.

Because of their mechanism of action, PDE5 inhibitors potentiate the effects of nitrates and may cause profound hypotension and death. Use of PDE5 inhibitors with any form of nitrates is contraindicated. Also, because PDE5 inhibitors are vasodilators, they may augment the hypotensive effects of antihypertensives. Patients should be warned about possible orthostatic symptoms. Doses of PDE5 inhibitors should be decreased in patients with significant liver or kidney disease, or in men taking P450 inhibitors.

There are many oral, nonprescription, non-FDA approved treatments for ED. Yohimbine is one of the most commonly used nonprescription treatments for ED. It blocks presynaptic α₂ receptors and may improve libido and increase blood flow into the penis. Based on reports from the authors’ patients, yohimbine is not an effective treatment of ED.

If patients fail VCDs and PDE5 inhibitors, the next step may be transurethral alprostadil (Medicated Urethral System for Erection or MUSE®). Alprostadil (prostaglandin E₁) increases cyclic adenosine monophosphate, resulting in vasodilatation and erection. Alprostadil can be given as an intraurethral pellet or by penile injection. The pellet is inserted into the urethra using a plastic applicator. It dissolves and is absorbed into the surrounding tissue producing an erection. It works in approximately 50% of older patients. Side effects include urethral burning, prolonged erections (priapism), and hypotension.

Alprostadil (Caverject® or Edex®) given as an intracavernosal injection (ICI) is a very effective treatment for ED. Unfortunately, it is the least-popular treatment because it requires an injection into the penis each time the patient wants to have intercourse. Penile pain, priapism, and penile fibrosis (Peyronie disease) are some of the side effects seen with ICI.

The first step is to assess goals and establish reasonable expectations. Medical conditions that contribute to sexual dysfunction should be addressed and medications reviewed to minimize sexual side effects.

Dyspareunia from atrophic vaginitis and decreased lubrication responds well to low-dose topical estrogen therapy (Table 46–3). The absorption of vaginal estrogen creams depends on the dose. In 2008, the FDA approved a low-dose conjugated estrogen cream regimen (0.3 mg twice weekly) as it does not cause significant proliferation of the endometrial lining. Vaginal estradiol rings or tablets deliver low-dose estrogen locally with low systemic absorption. In a Cochrane review, women favored the vaginal ring because of ease of use and comfort. According to the 2012 American Geriatrics Society Beers Criteria, low-dose vaginal estrogens are safe even in women with breast cancer, especially at dosages of estradiol <25 mcg twice weekly. Nonhormonal vaginal moisturizers with additional lubricants during intercourse are helpful for vaginal dryness, but they do not reverse the atrophic changes. Additionally, local stimulation through regular intercourse helps maintain a healthy vaginal mucosa. Longer foreplay allows more time for vaginal lubrication, just as older men often need longer and more direct stimulation to achieve an adequate erection.

Hypoactive sexual desire disorder with decreased libido may respond to a low-dose testosterone patch. Several randomized trials have demonstrated that low-dose testosterone patch improves sexual desire in women with decreased libido, taking systemic estrogen with or without progestin and either surgically induced or natural menopause. Androgenic side effects such as acne and hirsutism were uncommon and there was no decrease in high-density lipoprotein-cholesterol as seen in studies using oral methyltestosterone. More recently, it was demonstrated that the testosterone patch is also effective in women with natural or surgically induced menopause who have decreased libido and are not concurrent users of estrogens/progestin. The side-effect profile (hair growth) was acceptable to the women and did not make them discontinue the medication. Although testosterone patch seems effective, there is limited data on its long-term safety: 1 follow-up study demonstrated a good safety profile after 4 years of use in women taking estrogens (Nachtigall et al, 2011). A 300-mcg testosterone patch (Intrinsa®, Procter & Gamble Pharmaceutical) for postmenopausal women is available in Europe. In the United States, no testosterone formulation is FDA approved for women, pending more long-term safety data.

Treatment of urinary incontinence can improve sexual functioning, especially in patients with coital incontinence. If the coital incontinence is caused by detrusor overactivity, it can be cured in approximately 60% of patients with an antimuscarinic agent.

As the cause of sexual dysfunction in the older woman is often multifactorial, a team approach may be the most helpful. The primary care provider addresses medical issues and medication review. Physical/occupational therapists can improve function in the older woman with limited mobility. A gynecologic referral may be needed if dyspareunia is not caused by genital atrophy or does not respond to topical estrogens. A sex therapist can educate the older couple about sexuality and changes with aging. A couples therapist can address conflicts or poor communication between the couple and if there is underlying depression, anxiety or substance abuse other mental health referrals may be appropriate.