Sexual Medicine Update and Therapies for Menopausal Symptoms

From The 64th Annual Obstetrical And Gynecological Assembly Of Southern California

Educational Objectives

The goal of this program is to improve management of sexual disorders and of vasomotor symptoms in menopause. After hearing and assimilating this program, the clinician will be better able to:

1.   Apply the biopsychosocial model when evaluating patients with sexual dysfunction.

2.   List current treatments for sexual disorders.

3.   Implement sensate focus exercises in sexual therapy for couples.

4.   Describe current theories about underlying mechanisms of vasomotor symptoms in menopause.

5.   Assess risks and benefits of treatments for vasomotor symptoms in menopause.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the plan­ning committee to disclose relevant financial relationships within the past 12 months that might create any personal con­flicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Ishak has received research funding from Pfizer. Dr. Nathan and the planning committee reported nothing to disclose. In his lecture, Dr. Ishak presents information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgments

Drs. Ishak and Nathan were recorded at 64th Annual Obstetrical and Gynecological Assembly of Southern California, held April 3-4, 2009, in Marina Del Ray, CA, and sponsored by the Obstetrical and Gynecological Assembly of Southern Cali­fornia. The Audio-Digest Foundation thanks the speakers and the Obstetrical and Gynecological Assembly of Southern California for their cooperation in the production of this program.

Sexual Medicine Update

Waguih William Ishak, MD, Associate Clinical Professor of Psychiatry, David Geffen School of Medicine, Uni­versity of California, Los Angeles, and Program Director, Psychiatry Residence Training Program, Cedars-Si­nai, Los Angeles

Historical milestones: Sigmund Freud  —  first to talk about sexual issues and drive; first known sex therapist; Richard von Krafft-Ebing  —  wrote book on sexual disorders (Psychopathia Sexualis); treatment with sex hormones and concept of synthetic hormones developed between World War I and II; Alfred Kinsey  —  professor who performed survey of sexual habits; Masters and Johnson  —  witnessed »11,000 live sexual encounters in laboratory; examined physiologic and psychologic impact of sexual intercourse; established that vaginal and clitoral orgasm physiologi­cally identical; introduced sexual response cycle (arousal, plateau, orgasm, and resolution); developed intervention of sexual therapy; Helen Kaplan Singer  —  introduced desire as first phase of sexual response cycle; trained thera­pists who educated and brought patients to treatment; Ruth Westheimer ("Dr. Ruth")  —  sex education; Lou Ignarro  —  published research on nitric oxide, which led to introduction of sildenafil (eg, Viagra) in 1998; Berman sisters  —  focus on education and women’s health; Rosemary Basson  —  showed that male model of sexual response cycle not applicable to women (for women, desire and arousal intermix)

Biopsychosocial model: evaluation of biologic, psychologic, and social factors; biologic factors  —  genetic loading; impact of substances (eg, recreational drugs, alcohol, prescription drugs, over-the-counter drugs, herbal prepara­tions); medical conditions; genetic predisposition; evaluation of couple  —  infrequently done, but necessary for full evaluation of sexual disorders

Bringing up sexual issues: Journal of American Medical Association (Marwick 1999) survey  —  71% of patients thought physician would dismiss concerns; 68% afraid of embarrassing physician; speaker  —  asks patients about sexual history; moves into questions about sexual function; can take direct approach, or ask first how patient feels about answering such questions

Sexual Dysfunctions and Disorders

Overview: include disorders of sexual response cycle , plus pain (dyspareunia and vaginismus); each element inter­acts with all others

Biologic interventions: thorough physical examination and laboratory tests to rule out underlying medical conditions (eg, diabetes, hormonal imbalances); effect of substances  —  eg, selective serotonin reuptake inhibitors (SSRIs) widely prescribed, and shown to reduce desire by »60% (paroxetine [eg, Paxil] up to 85%); administration of med­ications, hormones, or devices  —  use hormones with great caution to correct deficiency or boost borderline values reflected in symptoms (can inhibit natural production)

Hypoactive sexual desire disorder: persistent or recurrent deficiency or absence of sexual fantasies or desire for sexual activity; must cause marked distress or interpersonal difficulty; rule out drug use or medical issues; distinctions  —  lifelong vs acquired; generalized vs situational; psychologic vs combination of causes (medical and psychologic factors not mutually exclusive); Chicago study  —  33% of women have hypoactive desire; can improve with age

Treatment: phosphodiestrase-5 inhibitors with SSRIs seem to improve desire, (but not speaker’s first choice of treatment for SSRI-related sexual dysfunction); bupropion (eg, Wellbutrin) study  —  nondepressed women given bupropion (150 mg twice daily); within 2 wk, desire improved in 29%  (due to dopaminergic effect); oral contra­ceptives (OCs)  —  studies suggest improvement in desire with discontinuation of mono- or biphasic OCs or switch to triphasic; perimenopausal patients  —  efficacy seen with hormone therapy using patches; testosterone  —via patch or topical ointment; monitor dosing carefully; patch not yet approved by United States Food and Drug Administration (FDA); examine woman’s relationship with partner before prescribing biologic intervention

Female arousal disorders: persistent or recurrent inability to attain or maintain adequate lubrication or swelling; un­derstand nature of stimulation, age of patient, and relationship with partner (ie, distinguish between situational and generalized dysfunction); prevalence  —  20% of women (vs »43% for overall sexual dysfunction)

Therapy: hormone replacement; topical estrogen  —  used to increase clitoral sensitivity; testosterone alone or in combination with estrogen (eg, Estratest); sildenafil  — placebo-controlled studies show improvement in lubrica­tion and arousal; not yet reproduced clinically; second choice to hormone therapy; clitoral vacuum devices (eg, EROS-CTD)  —  appear to improve genital sensation, vaginal lubrication, orgasmic abilities, and sexual satisfac­tion

Female orgasmic disorder: persistent recurrent delay or absence of orgasm; assess nature of stimulation; clinician must judge adequacy of sexual stimulation in context of patient’s sexual experience and age; only »30% of women able to reach orgasm through intercourse; 40% of women have difficulty achieving orgasm through inter­course alone

Therapy: vacuum device  —  helpful in premenopausal and postmenopausal women; sacral nerve stimulation (eg, InterStim)  —  observed to improve orgasmic dysfunction; option for highly motivated treatment-resistant patients; Kegel exercises  —  recommended by speaker; drugs  — little evidence of efficacy; cabergoline (eg, Dostinex) shows some promise (speaker has patent pending for precoital use)

Dyspareunia: look for organic causes; can be psychologic pain during intercourse, especially in patients exposed to sexual intrusions early in life (psychotherapy required); treatment  —  Kegel exercises; topical nitroglycerin appears effective

Vaginismus: introitus blocked; spasm in muscles of pelvic floor rather than upper vagina; caused by early sexual trauma, conflict with partner, or uncomfortable sexual position

Treatments: systemic desensitization using progressive dilation  —  not effective in speaker’s experience; intravenous diazepam abreaction  —  no longer used; botulinum toxin injections (University of Tehran study)  —  effective within 1 wk in 18 of 23 women given injections to sides of vagina; effects disappear in »4 to 5 mo

Psychologic and Alternative Interventions

Masters and Johnson's prescribed exercises: sensate focus I  —  pleasurable touching, excluding genitalia and breasts; partners take turns; patients return to therapy and relate details of touching (to desensitize about verbaliz­ing, encourage dialogue, and foster understanding of how to please partner); sensate focus II  —  includes breasts and genitalia; sexual intercourse forbidden; teach hand-guiding (allows one partner to show mate nonverbally which kinds of touching most pleasurable); if patients have sexual intercourse, evaluate whether appropriate to proceed or return to sensate focus I or II; sensate focus III  —  genital-to-genital touching; Masters and Johnson claimed tech­nique helps 90% of patients with erectile dysfunction, including diabetic patients

Sexual positions: no single optimal sexual position; stimulation of anterior vaginal wall  —  rear entry position; clito­ral stimulation  —  missionary position with woman’s pelvis elevated; Gräfenberg spot  —  some reports suggest evi­dence insufficient; other reports describe anatomic location

Alternative therapies: eg, acupuncture, herbs, aromatherapy; speaker encourages use

Investigational treatments: apomorphine (eg, Uprima)  — central agent that stimulates desire; side effect of vomit­ing; flibanserin  —  in phase III trials; alprostadil  —  not successful in women; placebo response  —  50% for treatment of sexual disorders (confounds research)

Alternative Therapies For Menopause  

 Lauren Nathan, MD, Associate Professor, Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles

Risk factors for vasomotor symptoms: lower body weight; smoking; ethnicity (Asian women less likely to com­plain of hot flushes than white women; in United States, black women more likely to report symptoms than white women)

Mechanisms of Vasomotor Symptoms

Overview: results from narrowing of hypothalamic thermoregulatory set point; increases chance of heat sensation in response to internal and external triggers; role of estrogen  —  acts at hypothalamus; exposure followed by with­drawal necessary, but not sufficient to elicit vasomotor symptoms; severity of symptoms does not correlate with es­trogen levels; hot flushes do not occur in all conditions associated with low estradiol levels

Proposed mechanisms: luteinizing hormone (LH) pulses or gonadotropins  —  do not mediate symptoms; eg, women with hypothalamic amenorrhea with LH pulses do not experience vasomotor symptoms; isolated gonadotropin de­ficiency does cause vasomotor symptoms; treatment with gonadotropin-releasing hormone agonists (which elimi­nate LH pulses) does produce vasomotor symptoms; opioids  —  do not play major role; eg, naloxone infusion reduces hot flushes and LH pulse frequency in some symptomatic menopausal women; decreased plasma b- endor­phin levels before hot flushes demonstrated in some but not all studies; estrogen-mediated change in serotonergic or noradrenergic systems  —  likely; evidence for norepinephrine  —  injection into hypothalamus causes peripheral vasodilation; gonadal steroids modulate adrenergic activity; baseline norepinephrine metabolites increase in symp­tomatic women with hot flushes; levels increase further after episode; clonidine (a₂-receptor agonist) ameliorates hot flushes in some women; yohimbine (a₂-receptor antagonist) increases flushing; evidence for serotonin  — receptors for 5-HT_1A and 2A important in thermoregulation; receptor expression and activity modulated by gonadal steroids; association between serotonin levels and severity of menopausal symptoms; exact relationship between serotonin and estrogen in thermoregulation unknown

Management of Vasomotor Symptoms

Estrogens: 80% to 90% effective (placebo response 20%-50%); dose-dependent; all routes of administration effec­tive; FDA-approved for treatment of vasomotor symptoms; studies show decreases in hot flush scores; some con­cerns about safety, thus alternatives increasingly important; no single agent addresses all symptoms

Progestins: effective at higher doses; side effects  —  fairly common; significant concern about effects on breasts and vasculature; higher rates of breast cancer in women using progestin vs estrogen alone; contraindications in meno­pausal patient similar to those for estrogen

SSRI therapy: efficacy differs with drug and with patient population; side effects  —  nausea, weight gain, sexual dys­function, and sleep disturbance; fluoxetine (eg, Prozac) study in breast cancer patients  —  8 wk of drug (20 mg) vs placebo; 50% decrease in hot flush score in both groups; some statistically significant benefit noted in crossover; paroxetine  —  studies show benefit for healthy women as well as  those with breast cancer; side effects may limit use; controversy remains as to whether responses modified by breast cancer; meta-analyses  —  suggest some im­provement in non-breast cancer population

Serotonin norepinephrine reuptake inhibitors (SNRIs): venlafaxine (eg, Effexor)  —  crossover phase of studies shows reduction in hot flush scores in women with and without history of breast cancer; side effects may limit use; desvenlafaxine  —  shown to be beneficial

Variation within and among SSRIs and SNRIs: causes  —effects on dopamine and norepinephrine reuptake; degree of anticholinergic effect; drug metabolism (eg, paroxetine and fluoxetine inhibit cytochrome P₄₅₀ [involved with ac­tivation or metabolism of tamoxifen]; may decrease hot flushes in women taking tamoxifen, but may reduce effi­cacy of breast cancer treatment)

Other neuroactive agents: gabapentin  —  effective at higher doses in women with breast cancer and general popula­tion; side effects may limit acceptance; 80% decrease in hot flush scores (40%-50% in placebo); clonidine  —  use established for treating flushes; minimal to modest efficacy; 40% discontinuation rate due to side effects; tibolone   —  not available in United States; effective for hot flushes; studied extensively in Europe, but safety ques­tionable (increased risk for breast cancer and endometrial hyperplasia reported in some studies)

Nonprescription remedies: lifestyle changes  —  lower ambient temperature; avoidance of hot beverages; paced respiration  —  somewhat effective; exercise  —  does not reduce symptoms, and strenuous activity can trigger symp­toms; phytoestrogens or isoflavones  —  soy and red clover sources; some studies show benefit (40-80 mg daily), but majority show no significant difference from placebo; fairly safe; increased risk for adverse estrogenic effects; short-term studies do not show change in endometrial thickness; black cohosh  —  herbal preparation; mechanism of action unknown; some studies show decrease in vasomotor symptoms with minimal risks; long-term studies lack­ing; additional herbs and interventions  —  evening primrose oil, ginseng, licorice, vitamin E, topical progesterone, and acupuncture; none shown effective

Bioidentical hormones: require prescription, but not approved by FDA; data on efficacy, side effects, and long-term safety lacking; North American Menopause Society (NAMS) statement  —  preparations presumed to carry known risks and benefits of standard hormone therapy; inform patient about lack of regulatory oversight

Dosing recommendations (NAMS): paroxetine  —  12.5 to 25 mg daily; fluoxetine  —  20 mg daily; venlafaxine  —  37.5 to 75 mg daily; can increase dose on weekly basis; gabapentin  —  300 mg daily, increasing to 300 mg tid; better to use at night due to sedative effect; clonidine  —  0.05 to 0.1 mg bid, or 0.1 mg daily patch; nonprescription alternatives  —  isoflavones and black cohosh with limit to 6-mo trial