Is Low Testosterone the Cause of Declining Sexual Function?

A 51-year-old woman presents to you with low libido for the past 1 year. She is monogamous with her husband and reports vaginal dryness and pain with penetrative sex. In the past 12 months, she has had three or four very light periods, and she suspects that she's in menopause because of increasing fatigue and weight gain, though she hasn't experienced significant hot flashes. Her medication list comprises only a daily multivitamin. Physical exam is notable for mild atrophy of the introitus and is otherwise unremarkable. Laboratory data are significant for low estradiol, elevated luteinizing hormone, and elevated follicle-stimulating hormone. Total testosterone, free testosterone, thyroid-stimulating hormone, prolactin, A1c, comprehensive metabolic panel, complete blood count, urinalysis, and sexually transmitted disease screening are normal. She would like to know what she can do to improve her sex life.

The female sexual response is a complex hormonal and psychological milieu that can't be effectively treated with just one modality. Some may think an issue like low libido is curable with only testosterone replacement, but other hormones like serotonin, dopamine, and norepinephrine may be at play.

Jessica R. Starr, MD

Prior to hormone optimization, it's important to address any psychological or physical concerns. Referral to a sex therapist or consultation with a psychiatrist is a recommended safe and effective first-step. A genitourinary exam, which may require coordination with the patient's ob/gyn, is necessary to rule out any structural issues.

This patient reported vaginal dryness and dyspareunia, which are common symptoms in perimenopause and contribute to an unpleasant sexual experience. We recommend treatment with vaginal estrogen applications as first-line therapy for genitourinary symptoms of menopause. A couple of common vaginal estrogen options include:

Estradiol cream (eg, Estrace)
Estradiol insert (eg, Vagifem, Estring, Imvexxy)

Be sure to instruct the patient to apply the medication to all affected areas (ie, the introitus, the labia, and inside the vaginal canal). Systemic hormone-replacement therapy, normally consisting of an estrogen and a progesterone, can be considered if the patient also has significant hot flashes.

Beverly G. Tchang, MD

Testosterone can be used off-label as a second-line agent if women are having disabling symptoms of sexual dysfunction despite estrogen therapy. Many women have low testosterone levels postmenopause, but these levels are not 100% correlated to their symptoms; most women have normal testosterone levels and can still experience a change in sexual function.

For hypoactive sexual desire disorder (HSDD), testosterone is an evidence-based therapy that has been shown to improve sexual function (eg, satisfactory sexual event frequency, sexual desire, pleasure, arousal, orgasm, and responsiveness).

Unfortunately, in the United States, there is no testosterone formulation approved for sexual dysfunction in women. Instead, we prescribe a 1% testosterone gel (eg, Vogelxo, Testim, Androgel), which delivers 12.5 mg of testosterone in one full pump. Because normal testosterone levels in women are about 10% of that in men, we instruct women to apply one tenth of the "male dose" (one full pump), which we often describe as a pea-sized amount. Caution should be used around younger children, female partners, and pets because the testosterone can transfer.

We strongly advise against compounded testosterone formulations, individually or alongside estrogen and progesterone preparations, particularly implantable pellets that release testosterone. None of these options are recommended by medical guidelines due to concerns regarding the lack of safety and efficacy data in these formulations.

Off-label testosterone therapy in women requires careful monitoring because even short-term supraphysiologic levels of testosterone can cause irreversible changes (eg, voice deepening). Physicians should:

Check total testosterone levels after 3-6 weeks of use and every 4-6 months thereafter
Check liver function tests every 6-12 months
Check cholesterol levels every 6-12 months
Ask about voice changes, acne, and hair growth

Oral testosterone formulations have been associated with riskier cardiometabolic profiles: higher low-density lipoprotein (LDL), the "bad" cholesterol; lower high-density lipoprotein (HDL), the "good" cholesterol; and increased weight. Transdermal testosterone preparations (eg, gels, patches) have not demonstrated this risk.

The biochemical goal of therapy is to improve total testosterone levels to the physiologic premenopause range. The clinical goal of therapy is to improve sexual functioning (eg, desire, arousal), which can take anywhere from 4-12 weeks from when therapy is initiated. Women with naturally higher levels of sex hormone–binding globulin (a protein that binds to testosterone in the blood) may not experience significant benefit from testosterone therapy.

Though testosterone is a commonly discussed female androgen, the dominant androgen in postmenopausal women is not in fact testosterone but rather an adrenal hormone: dehydroepiandrosterone sulfate (DHEA-S) The use of systemic DHEA therapy is not endorsed by any professional societies due to lack of efficacy in terms of improving sexual function or libido. However, an intravaginal product, Intrarosa, is a form of vaginal DHEA that has been proven to improve sexual desire, arousal, orgasm, satisfaction, dyspareunia, and vaginal dryness. It increases levels of DHEA, testosterone, and estrone in the blood. It has never been directly compared to vaginal estrogen, but it is a safe local androgen replacement for female patients with genitourinary symptoms of menopause.

This patient was prescribed vaginal estrogen per manufacturer instructions. She returned 3 months later reporting improvement in vaginal dryness and painful intercourse but still described the same lack of desire and arousal. After a discussion of the risks and benefits of off-label topical testosterone therapy, 1% testosterone gel was prescribed, and she was instructed to apply a pea-sized amount to her upper outer thigh once daily. Total testosterone levels 1 month later increased to normal premenopausal levels, and the patient reported improvement in her libido. Both vaginal estrogen and topical testosterone were continued as long-term medications along with appropriate monitoring.

For more diabetes and endocrinology news, follow us on Twitter and on Facebook

Follow Medscape on Facebook, Twitter, Instagram, and YouTube

Comments

Commenting is limited to medical professionals. To comment please Log-in.

Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.