Minding menopause: Psychotropics vs. estrogen? What you need to know now

TREATING HOT FLASHES IMPROVES MOOD

Until July 2002, estrogen was standard treatment for controlling hot flashes in patients such as Anne. Then the Women’s Health Initiative trial reported that estrogen’s health risks—heart attack, stroke, breast cancer, and blood clots—exceeded potential benefits during 5 years of therapy. As a result, fewer women want to take estrogen,⁶ and many Ob/Gyns are advising patients to get through menopause without hormones if they can.

For mild hot flashes—one to three per day—patients may only need vitamin E, 800 mg/d, and deep relaxation breathing to “rev down” the sympathetic nervous system when a hot flash occurs.

For moderate to severe hot flashes—four to 10 or more per day—estrogen replacement is the most effective therapy. Estradiol, 1 mg/d, reduces hot flashes by approximately 80 to 90%.⁷ Many small studies have shown that patients’ mood often improves as estrogen reduces their hot flashes.⁸ The recent Women’s Health Initiative Quality-of-Life study, however, reported that estrogen plus progestin did not improve mood in women ages 50 to 54 with moderate-to-severe vasomotor symptoms, even though hot flashes were reduced and sleep may have improved.⁹

New drugs of choice. Because of estrogen’s effectiveness in controlling hot flashes, some women and their doctors may choose to use it briefly (18 to 24 months). For others, psychotropics are becoming the drugs of choice for mood disorders with moderate to severe hot flashes.

The serotonin and norepinephrine reuptake inhibitor (SNRI) venlafaxine, 75 or 150 mg/d, has been shown to reduce hot flashes by 60 to 70%.¹⁰ A new trial is investigating whether duloxetine—an SNRI awaiting FDA approval—also reduces hot flashes. Other useful agents that have been shown to reduce hot flashes by 50% or more include:

• selective serotonin reuptake inhibitors (SSRIs) paroxetine CR, 12.5 mg/d to 25 mg/d,¹¹ citalopram, 20 to 60 mg/d,¹² and fluoxetine, 20 mg/d¹³
• gabapentin, 900 mg/d.¹⁴

For hot flashes and moderate to major depression, try an SNRI or SSRI first (see Algorithm), but consider the possible effects on sexual function. All SNRIs and SSRIs have sexual side effects, including anorgasmia and loss of libido in women and men. Among the psychotropics that improve hot flashes and mood, gabapentin is the only one that does not interfere with sexual function.

Mood improves, but still no libido

You and Ann decide on a trial of the SNRI venlafaxine, 75 mg/d, to treat her hot flashes and depressed mood. Four weeks later, her hot flashes are reduced by 50% in frequency and her mood has improved (Beck Depression Inventory score is now 10). She is feeling much better and wishes to continue taking the antidepressant.

She and her husband attempted intercourse once during the past month, although she wasn’t very interested. She did not achieve orgasm, despite adequate vaginal lubrication, and she did not enjoy the experience. “I still have no libido—zero, or even less,” she says.

TREATING LOW INTEREST IN SEX

Being angry with one’s partner is the number-one reason for decreased sexual desire in all studies. Therefore, consider couples therapy for any woman complaining of loss of interest in sex. In addition, eliminate—if possible—any medications she may be taking that have known sexual side effects, such as SSRIs or beta blockers.

If the patient complains of slow or no arousal, vaginal estrogen and/or sildenafil, 25 to 50 mg 1 hour before intercourse, may be beneficial.¹⁵ Other agents the FDA is reviewing for erectile dysfunction—such as tadalafil and vardenafil—may also help arousal problems in women.

Understanding how hormones affect female sexual desire also may help you decide what advice to give Anne and how you and her Ob/Gyn coordinate her care. For example, you might treat her sexual complaints and relationship problems while the Ob/Gyn manages symptoms of the vagina, uterus, and breast.

HOW TESTOSTERONE AFFECTS SEXUAL DESIRE

Testosterone is the hormone of sexual desire in men and women. Other female androgens include androstenedione, androstenediol, 5 α-dihydrotestosterone (DHT), dihydroepiandrosterone (DHEA), and its sulfate (DHEA-S). Premenopausal women produce these androgens in the ovaries (25%), adrenal glands (25%), and peripheral tissues (50%).

Average daily serum testosterone concentrations decline in women between ages 20 and 50. Lower levels are also seen with estrogen replacement therapy or oral contraceptives, lactation, anorexia nervosa, and conditions that reduce ovarian function. Women who undergo total hysterectomy with bilateral oophorectomy experience a sudden 50% loss of testosterone and an 80% decline in estradiol.¹⁶

Regularly menstruating women in their 40s and early 50s can have very low testosterone levels—at least 50% lower in the first 5 to 7 days of their cycles—than they had when they were in their 30s.¹⁷ The percentage of women reporting low libido increases with age until menopause, from 30% at age 30 to about 50% at age 50. Then the rate declines to 27% in women age 50 to 59.¹⁸ After natural menopause, luteinizing hormone (LH) continues to stimulate the ovarian hilar cells and interstitial cells to produce androgens, which is why many women at age 50 have adequate testosterone levels to sustain sexual desire.