Ask the Expert: Sexual Dysfunction Medication, Hormones, and Nutrition

Sexual dysfunction is a very common and distressing problem caused by diverse physical, psychological, lifestyle, and medication-related factors. When men and women seek treatment for sexual dysfunction at any age but particularly at midlife and beyond, what medications, hormonal and nutritional factors should the clinician consider and why?

When a patient presents with a sexual problem, the clinician first must attempt to determine the specific nature of the problem and its potential cause(s). Is the patient taking any of the numerous medications that may contribute to sexual dysfunction, such as antihypertensives, mood stabilizers, antidepressants, birth control pills, antipsychotics, cytotoxic agents, nonsteroidal anti-inflammatory medications, hormones, and antihistamines? Does the patient have a history of psychiatric illness or any medical conditions that may play a role, including hormonal imbalances and nutritional deficiencies? Below I review some of the evidence for sexual dysfunction related to hormonal and micronutrient deficiencies and discuss the potential relevance of hormone replacement and micronutrient supplementation.

Much has been written about the sexual side effects of the widely used selective serotonin reuptake inhibitor (SSRI) antidepressants (1). They cause sexual dysfunction through several mechanisms, including inhibition of cholinergic activity, inhibition of nitric oxide synthetase, reduction of dopaminergic activity, and increased release of prolactin (1). Sexual arousal is linked to cholinergic arousal activity. Nitric oxide synthetase is the enzyme responsible for the conversion of l-arginine to nitric oxide (NO), which, in turn, is critical for vasodilation in the genitals and other areas of the body. Dopamine (DA) is a neurotransmitter closely associated with sexual function. Prolactin is a pituitary hormone that causes sexual dysfunction when secreted in excess.

It is well known that adequate levels of testosterone (T) are critical for healthy sexual functioning in men and to a lesser degree in women (2, 3). T enhances NO activity and genital tissue engorgement. Although female erectile tissue responds to T and medications such as sildenafil (Viagra), which modulate NO, results for women treated with these medications are less clear.

Individuals who experience chronic insomnia have diminished T, in part because they spend insufficient time in the deep stages of sleep, when gonadotropin-releasing factor, which stimulates the release of sex hormones, is secreted. T deficiency may contribute to some psychiatric problems such as anxiety and depression, particularly with aging, although the data are not definitive (4–7).

Hypothyroidism is another common cause of sexual dysfunction, as well as psychiatric illness. Underactive thyroid glands in many patients are not diagnosed because they either are not tested for thyroid hormone levels or their laboratory tests are not comprehensive enough. Although a common practice, it is not adequate to obtain only thyroid-stimulating hormone and thyroxine levels to rule out thyroid dysfunction. Many patients have low levels of triiodothyronine (T3), the active form of thyroid hormone; therefore, a T3 and/or a free T3 level should be obtained.

Vitamin, mineral, and other nutritional deficiencies may contribute directly or indirectly to sexual dysfunction; the list, with putative mechanisms of action, is too long to consider here, and includes magnesium, zinc, iron, vitamins D and B complex, omega-3 fatty acids, amino acid precursors to neurotransmitters, and many others. As people age they absorb nutrients more poorly, which also could partially contribute to increasing sexual dysfunction with age.

Foods having poor nutritional quality that are consumed too often may have an indirect negative impact on sexual function. For example, too much fructose in the diet may deplete NO. Diets high in processed foods and low in beneficial grains, fruits, and vegetables contribute to obesity, metabolic syndrome, and systemic inflammation, all of which are associated with sexual, mood-related, and other medical problems (8).

Environmental toxins that act as endocrine disruptors (e.g., environmental estrogens) may be one reason for some types of sexual problems occurring in men at younger ages.

Thus, there are many new factors to consider when one is assessing sexual function and there is far too little definitive research to date and few treatment algorithms that will help all patients, although some exist (9). The potential relevance of nutritional deficiencies to sexual function over the longer term should not be discounted. Here, only a few examples of the mechanisms by which these substances may affect sexual functioning are highlighted:

• Magnesium. Magnesium deficiency impairs penile engorgement, because it is required for the production of NO and acetylcholine and necessary for smooth muscle relaxation in the corpus cavernosum, which enables erection.

• Magnesium also is a cofactor in the synthesis of the sex-positive neurotransmitter DA. Magnesium deficiency is associated with insomnia, which can impair sexual functioning indirectly by interfering with testosterone production. Magnesium deficiency also is associated with anxiety and depression, because magnesium is a cofactor in serotonin (5-HT) production. Patients who are anxious and depressed often experience sexual dysfunction, even when they are not taking antidepressant medication.

• Magnesium deficiency is very prevalent in the general population, for reasons too numerous to detail here. Obesity is associated with magnesium deficiency, systemic inflammation, and sometimes sexual dysfunction and its prevalence is increasing. Common dietary habits such as drinking alcohol and coffee and consuming too much salt can remove magnesium from the body, as can the use of diuretics.

• Vitamin D. Vitamin D aids the synthesis of brain neurotrophic factors necessary for the synthesis of tyrosine hydroxylase, the limiting enzyme in catecholamine synthesis (10). DA, along with epinephrine and norepinephrine, is a catecholamine. Hence, vitamin D deficiency may contribute to sexual problems by limiting DA availability. It also may contribute to depression in a more general way by limiting catecholamine availability. Vitamin D also aids in absorption of magnesium.

• B-Complex Vitamins. Vitamin B₆ is a cofactor both for DA and 5-HT synthesis. Vitamin B₆ also supports sex hormone production and aids in magnesium absorption.

• Vitamin B₁₂ is a cofactor in the synthesis of S-adenosyl methionine, which is synthesized from folate, and is a necessary cofactor in the synthesis of DA, epinephrine, and other catecholamines. Thus, vitamin B₁₂ and folate deficiencies may also contribute to lack of adequate DA and sexual dysfunction. Vitamin B₁₂ deficiency is widespread and often related to malabsorption.

Below I summarize what the above suggests for treatment:

• Antidepressants. Patients with SSRI-induced sexual dysfunction may do well when switched to bupropion, an antidepressant known for not causing sexual dysfunction. However, some patients cannot tolerate its side effects. An alternative would be the addition of an oral medication used to treat erectile disorder.

• Testosterone supplementation. In cases of deficiency, T supplementation mitigates sexual and possibly psychiatric problems. T supplementation in depressed men and women may help alleviate depression as well as sexual dysfunction (11–13), but the picture is complicated. T is available in intramuscular injections of testosterone cypionate, as well as in topical creams, gels, and patches in the United States for men only. It is available for women in Europe in the form of a patch.

• Magnesium. Magnesium may be supplemented as readily absorbable magnesium glycinate, 200–500 mg/day. It also can be absorbed via Epsom salt baths and topical cream preparations. Levels may be best monitored via red blood cell magnesium levels, as opposed to serum levels, which are less sensitive for detecting deficiencies.

• Vitamin D. Vitamin D supplementation can range from 800 to 4,000 IU b.i.d., orally, depending upon the severity of the deficiency. Levels should be monitored and maintained between 50 and 100 ng/ml.

• B-Complex Vitamins. Vitamin B₆ may be taken alone, 50–100 mg/day, or in combination with other B vitamins, as an oral B complex tablet or sublingual liquid. Vitamin B₁₂ may be taken intramuscularly and sublingually or supplied in the form of a patch.

• Other supplements.

• Some supplements mentioned in the literature as enhancing sexual function include kava kava, Rhodiola rosea, phosphatidyl serine, phosphatidyl choline, l-arginine, Pycnogenol, and acetyl-l-carnitine. The scientific evidence for these is still minimal or conflicting.

In conclusion, when patients present with sexual dysfunction, it is important to consider their medical conditions, medications, and hormones and also their overall nutritional and micronutrient status. Counseling or psychotherapy also may be warranted. Evaluating and supplementing for hormonal (T and thyroid) and micronutrient deficiencies may help patients with sexual dysfunction and also may reduce symptoms of depression and anxiety, improve health, and promote greater well-being and vitality, which in turn can improve sexual function. Attention to nutritional recommendations is sensible, mostly evidence-based, and safe.

Patients should be strongly encouraged to improve their diet (toward a Mediterranean-type diet) and lifestyle (stop smoking, exercise more, lose weight, sleep 7 hours minimum, and reduce stress) to reduce the burden of systemic inflammation and to improve general, mental, and probably sexual health. These lifestyle changes also may reduce hypertension, closely associated with erectile dysfunction (14). Ultimately these healthful practices also may reduce the need for drugs and supplements.

Medical school nutrition curricula often are acknowledged to be insufficient and out-of-date (15). Many physicians now recognize the need to increase their knowledge of nutritional interventions to improve many aspects of their patients' health. High-quality CME and online nutrition courses geared toward practicing physicians are available. My growing experience with observable benefits of a multifaceted integrative treatment approach leads me to recommend it to other physicians for their patients' improved sexual and mental health.