Minding Psychotropics vs. ?

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What you need to know now

Louann Brizendine, MD sychiatrists are suddenly viewed as experts in treating menopause-related Clinical professor of psychiatry Director, Women’s Mood and Clinic Pmood problems because of our expertise with using Langley Porter Psychiatric Institute psychotropics. Practically overnight, the Women’s University of California, San Francisco Health Initiative studies1,2 have made women and their doctors think twice about using estrogen. Instead, many are turning to psychiatric medica- tions that have been shown to improve both mood and hot flashes—without estrogen’s potential risks. Chances are good that after an Ob/Gyn has tried one or two psychotropics without success or with too many side effects, he or she will ask a psychiatrist to consult for certain patients. How Psychotropics have become well-prepared are you to assume this role? If your recall of female reproductive physiol- a first-line therapy for hot flashes ogy from medical school is incomplete, read on about one approach to a perimenopausal patient and in perimenopause. with depressed mood. This review can help you: Will you be ready when Ob/Gyns • discuss menopause knowledgeably when other physicians refer their patients to you call you for help? • provide effective, up-to-date treatments for menopause-related mood and sexual problems, using psychotropics or , alone or in combination.

Irritable, with no interest in sex Anne, age 51, has been referred to you for complaints of depressed mood and low . She says she has become irri- table and snaps easily at her two children and her

VOL. 2, NO. 10 / OCTOBER 2003 13 Menopause

Table 1 factors, or they may result Why mood problems may occur during menopause from a domino effect trig- gered by declining estro- Hypothesis Explanation gen levels (Table 1). Psychodynamic Onset of menopause is a critical life event and a Women who experience readjustment of self-concept vasomotor symptoms such Sociologic Mood changes are caused by changing life as hot flashes are at 4.6 circumstances at menopause (‘empty nest,’ aging times greater risk for parents, health changes) depression than those who 5 Domino Depressed mood is caused by hot flashes due to are -free. declining estrogen levels, which cause chronic Hot flashes begin on sleep deprivation with subsequent and average at age 51, which is memory and mood changes also the average age when Biochemical Decreasing estrogen leads to neurochemical natural menopause begins. changes in the brain (serotonin, dopamine, During menopause, most cholinergic, GABA, norepinephrine) women (82%) experience hot flashes (suddenly feel- ing hot and sweating dur- husband. She has no interest in sex, no urge to ing the day), warm flushes (a sensation of warmth masturbate, and has had no for 6 or heat spreading over the skin), and months. (Table 2). All women who undergo surgical meno- Anne also complains of , dry hair and pause experience hot flashes. skin, warm flushes, and painful joints. She has no Hot flashes are moderate to severe for 40% of personal or family history of depression. She is not women who experience them and persist for 5 to suicidal but states that she really doesn't want to 15 years. By definition, moderate to severe hot live anymore if “this is it.” flashes occur 6 to 10 or more times daily, last 6 to 10 minutes each, and are often preceded by anxi- HOT FLASHES: A SPARK FOR DEPRESSION ety, , irritability, nervousness, or panic. Women who experience their first depression after age 50 do not fit the usual DSM-IV diag- A marriage under stress Anne says that her hus- nostic criteria for depression. The Massachusetts band is angry about the lack of sexual intercourse, Women’s Health Study3 found that 52% of and she feels the stress in their marriage. She also women who experience depressed mood in the is worrying about her children leaving for college perimenopause have never had a depression and about her mother's ill health. before. This study also found a correlation She scores 20 on the Beck Depression between a longer perimenopause (>27 months) Inventory, which indicates that she has mild to mod- and increased risk of depressed mood. At the erate depression. Her menstrual periods remain reg- same time, women who have had a prior depres- ular, but her cycle has shortened from 29 to 24 days. sion are 4 to 9 times more likely to experience She reports experiencing some hot flashes that depressive symptoms during perimenopause than wake her at night and says she hasn't those who have never had a depression before.4 had a good night’s sleep in months. The increased mood symptoms may be relat- Laboratory tests show FSH of 25 mIU/mL and ed to psychodynamic, sociologic, or biochemical inhibin B <45 pg/mL. Her estradiol is 80 pg/mL, continued on page 16

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continued from page 14 Table 2 their doctors may choose to use it Symptoms of menopause related to decreased estrogen briefly (18 to 24 months). For oth- ers, psychotropics are becoming Brain Irritability, mood swings, depressed mood, forgetfulness, the drugs of choice for mood dis- low sex interest, sleep problems, decreased well-being orders with moderate to severe Body Hot flashes, vaginal dryness, painful intercourse, fatigue, hot flashes. joint pain, pain with , bladder dysfunction The serotonin and norepi- nephrine reuptake inhibitor (SNRI) , 75 or 150 which is not yet in the menopausal range of 10 to 20 mg/d, has been shown to reduce hot flashes by 60 pg/mL. Her stimulating hormone (TSH) is to 70%.10 A new trial is investigating whether normal. Her endocrinologic and reproductive diag- duloxetine—an SNRI awaiting FDA approval— nosis is perimenopause. also reduces hot flashes. Other useful agents that have been shown to reduce hot flashes by 50% or TREATING HOT FLASHES IMPROVES MOOD more include: Until July 2002, estrogen was standard treatment • selective serotonin reuptake inhibitors for controlling hot flashes in patients such as (SSRIs) CR, 12.5 mg/d to 25 mg/d,11 Anne. Then the Women’s Health Initiative trial citalopram, 20 to 60 mg/d,12 and fluoxetine, 20 reported that estrogen’s health risks—heart attack, mg/d13 , cancer, and blood clots—exceeded • , 900 mg/d.14 potential benefits during 5 years of therapy. As a For hot flashes and moderate to major depres- result, fewer women want to take estrogen,6 and sion, try an SNRI or SSRI first (see Algorithm, page many Ob/Gyns are advising patients to get 22), but consider the possible effects on sexual func- through menopause without hormones if they can. tion. All SNRIs and SSRIs have sexual side effects, For mild hot flashes—one to three per day— including and loss of libido in women patients may only need vitamin E, 800 mg/d, and men. Among the psychotropics that improve and deep relaxation breathing to “rev down” the hot flashes and mood, gabapentin is the only one sympathetic nervous system when a hot flash that does not interfere with sexual function. occurs. For moderate to severe hot flashes—four to 10 Mood improves, but still no libido You and Ann or more per day—estrogen replacement is the decide on a trial of the SNRI venlafaxine, 75 mg/d, most effective therapy. , 1 mg/d, reduces to treat her hot flashes and depressed mood. Four hot flashes by approximately 80 to 90%.7 Many weeks later, her hot flashes are reduced by 50% in small studies have shown that patients’ mood frequency and her mood has improved (Beck often improves as estrogen reduces their hot Depression Inventory score is now 10). She is feel- flashes.8 The recent Women’s Health Initiative ing much better and wishes to continue taking the Quality-of-Life study, however, reported that . estrogen plus progestin did not improve mood in She and her husband attempted intercourse women ages 50 to 54 with moderate-to-severe once during the past month, although she wasn’t vasomotor symptoms, even though hot flashes very interested. She did not achieve orgasm, were reduced and sleep may have improved.9 despite adequate , and she did not New drugs of choice. Because of estrogen’s effec- enjoy the experience. “I still have no libido—zero, or tiveness in controlling hot flashes, some women and even less,” she says.

continued on page 21

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continued from page 16 TREATING LOW INTEREST IN SEX their cycles—than they had when they were in Being angry with one’s partner is the number- their 30s.17 The percentage of women reporting one reason for decreased in all stud- low libido increases with age until menopause, ies. Therefore, consider couples therapy for any from 30% at age 30 to about 50% at age 50. Then complaining of loss of interest in sex. In the rate declines to 27% in women age 50 to 59.18 addition, eliminate—if possible—any medica- After natural menopause, tions she may be taking that have known sexual (LH) continues to stimulate the ovarian hilar cells side effects, such as SSRIs or beta blockers. and interstitial cells to produce , which If the patient complains of slow or no arousal, is why many women at age 50 have adequate vaginal estrogen and/or sildenafil, 25 to 50 mg 1 levels to sustain sexual desire. hour before intercourse, may be beneficial.15 Oral estrogen replacement therapy reduces Other agents the FDA is reviewing for erectile bioavailable testosterone by 42% on average, dysfunction—such as tadalafil and vardenafil— which can induce deficiency in a may also help arousal problems in women. menopausal woman.19 The increased estrogen Understanding how hormones affect female inhibits pituitary LH and decreases stimulation of sexual desire also may help you decide what the androgen-producing cells in the .20 advice to give Anne and how you and her Female androgen deficiency. A number of papers Ob/Gyn coordinate her care. For example, you have been published on female androgen defi- might treat her sexual complaints and relation- ciency syndrome (FADS).21 Its diagnosis requires ship problems while the Ob/Gyn manages symp- symptoms of thinning pubic and axillary hair, toms of the , , and breast. decreased body odor, lethargy, low mood, dimin- ished well-being, and declining libido and HOW TESTOSTERONE AFFECTS SEXUAL DESIRE orgasm, despite adequate estrogen but low levels Testosterone is the hormone of sexual desire in of testosterone and DHEA. men and women. Other female androgens include , , 5 - TREATING TESTOSTERONE DEFICIENCY dihydrotestosterone (DHT), dihydroepiandros- Benefits of replacement therapy. Replacing testos- terone (DHEA), and its sulfate (DHEA-S). terone in women with FADS can improve mood, Premenopausal women produce these androgens well-being, motivation, cognition, sexual func- in the (25%), adrenal glands (25%), and tion related to libido, orgasm, sexual fantasies, peripheral tissues (50%). desire to masturbate, and nipple and clitoral sen- Average daily serum testosterone concentra- sitivity.22 Muscle and stimulation and tions decline in women between ages 20 and 50. decreased hot flashes are also reported.23 Women Lower levels are also seen with estrogen replace- with androgen deficiency symptoms and low ment therapy or oral contraceptives, , testosterone at menopause should at least be con- anorexia nervosa, and conditions that reduce ovar- sidered for physiologic testosterone replacement. ian function. Women who undergo total hysterec- Risks of replacement therapy. Androgen replace- tomy with bilateral experience a ment therapy does carry some risks, which need sudden 50% loss of testosterone and an 80% decline to be discussed with the patient. Testosterone in estradiol.16 may lower levels of beneficial HDL cholesterol, Regularly menstruating women in their 40s so get the cardiologist’s clearance before you give and early 50s can have very low testosterone lev- testosterone to a woman with heart disease or an els—at least 50% lower in the first 5 to 7 days of HDL cholesterol level <45 mg/dL.

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Algorithm Managing mood and libido problems during perimenopause Female patient age 45 to 55 with depressed mood (Baseline Beck Depression Inventory score >15) Hot flashes moderate to severe (4 to 10 or more daily)

YES ▼ YES Wishes to take systemic estrogen? NO ▼ ▼ Estrogen (patch, pill or gel) + progestin SNRI or SSRI antidepressant plus if patient has intact uterus and not menstruating vaginal estrogen if needed for vaginal dryness ▼ ▼ YES Hot flash frequency reduced? NO YES Hot flash frequency reduced? ▼ NO ▼ Increase SNRI/SSRI dosage, Increased estrogen and/or add add estrogen, or switch SNRI, SSRI, or gabapentin to gabapentin ▼ ▼ ▼ ▼ YES Mood improved? NO YES Mood improved?

▼ NO ▼ Add or replace with SNRI or SSRI Increase SNRI/SSRI or gabapentin dosage ▼ ▼ and/or add estrogen

Low libido complaints? ▼

▼ (Sexual Energy Scale <5)

YES NO ▼ ▼

Patient reports distress Monitor mood and libido ▼ NO

because of low sexual interest? ▼ during follow-up visits ▼

YES ▼ Measure serum testosterone and SHBG and calculate Free Androgen Index ▼ NO Consider couples therapy Low free androgen index? ▼

YES ▼ Discuss testosterone replacement Not recommended with patient ▼

▼ Recommended ▼ Begin low-dose testosterone (pill, gel or ) • Instruct patient to monitor libido daily with Sexual Energy Scale (SES) • Adjust dosage based on SES and monthly free androgen index until desired result is reached • Consider couples therapy

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A meta-analysis of eight clinical trials found Table 3 no changes in liver function in menopausal Free androgen index (FAI) values women taking 1.25 to 2.5 mg/d of methyl testos- in women, by age terone. Liver toxicity has been reported in men Replacing a woman’s bioactive testosterone 24 using 10-fold higher testosterone dosages. to the normal free androgen index range for At the normal level of testosterone, darkening her age may improve low libido. and thickening of facial hair are rare in light- How to calculate FAI skinned, light-haired women but can occur in Total testosterone in nmol/L (total testosterone dark-skinned, dark-haired women. Increased in ng/ml X 0.0347 X 100), divided by sex irritability, excess energy, argumentativeness, and hormone-binding globulin (SHBG) in nmol/L. aggressive behavior have been noted if testos- Age Normal range terone levels exceed the physiologic range. 20 to 29 3.72 to 4.96 Controlled, randomized studies are needed 30 to 39 2.04 to 2.96 to assess the effects of long-term use (more than 40 to 49 1.98 to 2.94 24 months) of testosterone replacement in women. 50 to 59+ 1.78 to 2.86 Challenges in measuring testosterone levels. Serum Source: Guay et al, reference 28. free testosterone is the most reliable indicator of a woman’s androgen status, but accurately measur- testosterone, free testosterone, DHEA, and ing testosterone levels is tricky: DHEAS. Measuring SHBG will help you deter- • Only 2% of circulating testosterone is mine the free, biologically active testosterone unbound and biologically active; the rest is level and calculate the Free Androgen Index bound to sex hormone-binding globulin (SHBG) (FAI) for women (Table 3).28 or albumin. • In ovulating women, serum testosterone A candidate for testosterone therapy? Now that levels are higher in the morning than later in the Anne’s mood, sleep, and hot flashes have improved day and vary greatly within the . with venlafaxine, she wants help with her lack of • Levels of androgens and estrogen are high- sexual interest. You measure her testosterone and est during the middle one-third of the cycle—on SHBG levels and find that her free androgen index days 10 to 16, counting the first day of menstrual is very low at 0.51 (normal range, 1.78 to 2.86). as day 1.25 In collaboration with her Ob/Gyn, you and Anne • Oral contraceptives also decrease andro- decide to start her on testosterone replacement gen production by the ovary and can result in low therapy. You prescribe Androgel, starting at 1/7th of libido in some women.26 a 2.5-mg foil packet (0.35 mg/d of testosterone), Tests developed to measure testosterone lev- and instruct her to rate her sexual energy daily, els in men are not sensitive enough to accurately using a Sexual Energy Scale. measure women’s naturally lower serum concen- trations, let alone the even lower levels character- TESTOSTERONE CHOICES FOR WOMEN istic of female androgen or testosterone deficien- Replacing a woman’s bioactive testosterone level cy. New measurements and standardization of to the normal free androgen index range for her normal reference ranges have been developed for age group may improve low libido. Some low- women complaining of low libido.27 dose testosterone replacement options include: Tests for androgen deficiency include total • methyl testosterone sublingual pills, 0.5 mg/d, continued on page 27

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continued from page 23 made by a compounding pharmacy or Figure 1 reduced dosages of oral pills made for men. How to use the Sexual Energy Scale If you prescribe methyl testosterone, rou- to monitor response to therapy tine lab tests will not accurately measure This scale is designed for screening patients experiencing serum testosterone levels—unless you substance-induced or sexual dysfunction due order the very expensive test that is specific to a general medical condition. It can be given at every visit, for methyl testosterone. including at baseline, to evaluate a patient’s sexual energy level, which includes ease of arousal, sexual pleasure, , interest • 2% vaginal cream, applied topically to in sex, sexual fantasies, and sexual fulfillment. increase clitoral and genital sensitivity. It Patient instructions: On a scale of 1 to 10, circle the number that may increase blood levels moderately indicates your current sexual energy level. through absorption Lowest sexual energy Highest sexual energy • Androgel, a topical testosterone level in life level in adult life approved for men. As in Anne’s case, start with 0.35 mg/d or one-seventh of the 2.5 12345678910 mg packet (ask the pharmacist to place this Source: Reprinted with permission. Copyright 1997 JK Warnock, Department of amount in a syringe). Instruct the patient to Psychiatry. University of Oklahoma Health Sciences Center, Tulsa. apply the gel to hairless skin, such as inside the forearm. Effects last about 24 hours, and you can measure serum levels accurately A vaginal lubricant is not sufficient to avoid age- after 14 days. Vaginal throbbing—a normal related vaginal , which may make inter- response—may occur within 30 minutes of course difficult or impossible. testosterone application. The FDA is considering other testosterone Libido improves modestly Ann returns in 4 weeks preparations—including a testosterone patch for with gradually improving sex drive (Sexual Energy women and a gel in female-sized doses. Score is now 5). She had sexual intercourse twice in Using the Sexual Energy Scale. To monitor for a the past month and didn’t “dread” it, but also did therapeutic response, ask the patient to use the not enjoy it or reach orgasm. You have told her that Sexual Energy Scale (Figure 1).29,30 Instruct her to venlafaxine may slow or prevent orgasm, but she define her “10” as the time in life when she had wants to keep taking it. She reports that her marital the most fulfilling sexual life, was the most easily relationship is improving. aroused, had the most sexual pleasure, and the You order repeat testosterone and SHBG blood best orgasms. Her “1” would be when she felt the levels and find her free androgen index has worst sexually and had the least desire. improved to 1.10, which is still low. You increase the Giving supplemental estrogen. If you prescribe Androgel dosage to 1/5th of a 2.5 mg packet (0.5 estrogen plus testosterone (Estratest), start with mg/day) and continue to monitor Anne’s Sexual Estratest HS, which contains 0.625 mg esterified Energy Scale ratings at monthly follow-up visits. and 1.25 mg of methyl testosterone. She has set a Sexual Energy Scale rating of 7 to 8 Add a progestin if the patient is postmenopausal as her target. Anne says she appreciates your help and has not had a , to protect the with—as she puts it—“this embarrassing problem.” uterus from endometrial hyperplasia. Women with vaginal dryness also need sup- For additional information, see “Physiology 101: plemental estrogen, which can be applied vagi- How endocrine changes affect mood and libido nally (such as Premarin cream or Estrace cream). during menopause,” pages 28-30.

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PHYSIOLOGY 101 How endocrine changes affect mood and libido during menopause Louann Brizendine, MD edicine’s understanding of menopause’s their early 40s are exposed to high levels of estro- Mphysiologic and psychological conse- gen in some menstrual cycles and low levels in quences is changing, just as the “baby-boom” others. Excess estrogen thickens the endometri- generation is navigating this passage called the um—causing heavier bleeding—and stimulates change of life. Many midlife women are unaware fibroid growth, which is the leading reason for that the menopause transition does not begin . around age 50 but spans 30 years—from ages 35 One in four American women undergoes to 65. Natural menopause begins 15 years before surgical menopause. The average age of the and ends 15 years after ceases—as 700,000 U.S. women who undergo hysterectomy the brain and tissues adjust to first fluctuating each year is 40 to 44. Women who have had a hys- then decreased estrogen levels. It occurs in three terectomy and have mood symptoms and sexual phases—early menopause, perimenopause, and adjustment problems are likely to see psychia- late menopause—that reflect a progression of trists earlier than women who undergo a more hormone changes. gradual natural menopause.

EARLY MENOPAUSE: ACCELERATES PERIMENOPAUSE: HOT FLASHES, DRY VAGINA At approximately age 35, the ovaries start produc- At ages 45 to 55, most women (90%) who have ing lower levels of inhibin—a glycoprotein that not had a hysterectomy start to cycle irregularly, inhibits pituitary production of follicle-stimulat- tending at first toward shorter cycles and then ing hormone (FSH) (Figure 2). Less inhibin skipping periods. Some periods are heavier and means less negative feedback to the pituitary and some lighter than usual. The remaining 10% of an increase in pituitary FSH production. More women continue to cycle regularly until their FSH means more activin—an ovarian glycopro- menstrual periods stop abruptly. tein that stimulates ripening of —and so Many women notice temperature dysregula- ovulation begins to accelerate at approximately tion during perimenopause. When they exercise, age 36. Activin stimulates more and more eggs in their cool-down times may double. Menopausal the ovary to develop faster and faster. symptoms such as hot flashes occur when estro- By age 37, the ovarian reserve starts to gen levels drop below the point that some decline, and—because FSH has increased—the researchers call a woman’s “estrogen set point.” follicle is driven to produce greater amounts of Screening for estrogen decline. When you see estrogen. Estrogen serum levels in fertile women a patient in your office, you can often determine average 100 pg/mL. During perimenopause, whether her affective symptoms—irritability, estrogen levels sometimes soar to 300, 400, or mood swings, depressed mood, and forgetful- even 500 pg/mL, then may crash down to 50 to 80 ness—might be related to estrogen decline by pg/mL.These wild fluctuations are thought to asking two screening questions: trigger , sleep disturbance, mood • Are you having any warm flushes or hot swings, and sexual complaints in some women. flashes? Hysterectomy and mood symptoms. Women in • Do you have vaginal dryness?

28 VOL. 2, NO. 10 / OCTOBER 2003 MENOPAUSE Figure 2 Normal female reproductive cycle: The rhythm of the hypothalamic-pituitary-ovarian axis

INTERNAL & ENVIRONMENTAL STIMULI PHYSIOLOGY 101 1 1 Hypothalamic neurons produce pulses of luteinizing hormone releasing hormone (LHRH)— HYPOTHALAMUS formerly called -releasing hormone (GnRH)—under the influence of internal and environmental stimuli and circulating levels of Neuronal input estrogen and .

5 5 2 LHRH passes through the hypophyseal portal + – – system and stimulates the to secrete follicle stimulating hormone (FSH) and luteinizing hormone (LH). Hypophyseal 2 LHRH portal system 3 Circulating levels of FSH and LH stimulate (+) the ovary to produce activin, a glycoprotein that PITUITARY activates eggs in the follicle and promotes GLAND ovulation. FSH and LH also stimulate the 5 5 secretion of estrogen (estradiol), progesterone, and testosterone. – + – – 4 At the same time, inhibin—another glycoprotein produced by the ovary—inhibits (-) the production of FSH by the pituitary gland. Inhibin 4 LH FSH 5 Through a feedback loop, circulating estrogen and progesterone act on LHRH in the + hypothalamus to increase (+) or decrease (-) the 3 pulsatility (rhythm) of the hormones controlling OVARY + the menstrual cycle. They also modulate the production of FSH and LH by the pituitary gland. Estrogen Activin Progesterone Illustration for CURRENT PSYCHIATRY by Jennifer Fairman

LATE MENOPAUSE: ESTROGEN LOW, MOOD UP often will open a discussion of the couple’s sexu- During late menopause, approximately age 55 al and emotional relationship. and older, women commonly complain of vaginal Other physiologic changes caused by estro- dryness, hot flashes, night sweats, sleep problems, gen and androgen deficiency include thinning and fatigue. Sexual interest may decrease, and a —including pubic, auxiliary, and leg decline in sexual activity can become a problem hair—decreased body odor, thinning skin, wrin- for some couples. Asking “How is your ?” kling skin, and decreasing . continued

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Table 4 Three phases of menopause: A 30-year process

Early Middle (perimenopause) Late Ages 35 to 45 Ages 46 to 55 Ages 56 to 65+

PHYSIOLOGY 101 Physiologic changes Ovary starts producing less Irregular menstrual cycles, Depletion of eggs and follicle inhibin 15 years before with shorter cycles, skipping menses stop periods for 90% of women Decreased inhibin increases Some periods heavier, some MENOPAUSE FSH and stimulates follicle lighter than usual to produce more estrogen Increased estrogen thickens and leads to heavier menstrual bleeding and increased risk of fibroids Increased FSH produces more activin, which makes eggs develop faster and accelerates egg depletion

Lab values Menses: Normal Cycle shorter (24-26 days) None for >12 months FSH day 3: 10-25 mIU/mL 20-30 mIU/mL 50-90 mIU/mL Estradiol day 3: 40-200 pg/mL 40-200 pg/mL 10-20 pg/mL Inhibin B day 3: Varies <45 pg/mL 0

Symptoms Headaches, sleep Warm flushes, hot flashes, Vaginal dryness, hot flashes, disturbances, mood swings, night sweats in 82% of night sweats, sleep problems, urinary problems, sexual women (moderate to severe fatigue, sexual interest changes, complaints in 40%) thinning body hair (pubic, legs, axillary), decreased body odor, thinning skin, wrinkling skin, decreasing bone density, BUT mood starts to stabilize FSH: follicle-stimulating hormone

Urinary symptoms. Bladder problems and uri- Despite sometimes-difficult physiologic nary symptoms are persistent symptoms of changes, the good news for many women is that menopause for 75% of women. Although we psy- mood symptoms start to stabilize after peri- chiatrists don’t review the , it is menopause (Table 4). Women whose moods are important to remember that embarrassment very responsive to hormonal fluctuations—such because of during sex may as those with severe or have a lot to do with a woman’s “loss of interest” premenstrual dysphoric disorder—sometimes get in sexual intercourse. much better after menopause.

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References 1. Burger H. Hormone replacement therapy in the post-Women's Related resources Health Initiative era. Climacteric 2003;6(suppl 1):11-36. The Women’s Health Site. Duke Academic Program in Women’s 2. Grodstein F, Clarkson TB, Manson JE. Understanding the diver- Health. www.thewomenshealthsite.org gent data on postmenopausal hormone replacement therapy. N Engl J Med 2003;348-645-50. Massachusetts General Hospital Center for Women’s Mental 3. Joffe H, Hall JE, Soares CN, et al. Vasomotor symptoms are associ- Health. www.womensmentalhealth.org ated with depression in perimenopausal women seeking primary care. Menopause 2002;9(6):392-8. DRUG BRAND NAMES Citalopram • Celexa Paroxetine • Paxil 4. Soares CN, Almeida OP, Joffe H, Cohen LS. Efficacy of estradiol Fluoxetine • Prozac Sildenafil • Viagra for the treatment of depressive disorders in perimenopausal women: Gabapentin • Neurontin Venlafaxine • Effexor a double-blind, randomized, -controlled trial. 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