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Der weibliche Orgasmus Physiologie und Pathophysiologie, hormonelle Einflüsse und weibliche Orgasmusstörung PD Dr. med. Petra Stute Universitätsklinik für Frauenheilkunde Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Was muss ich wissen, um „es“ nicht faken zu müssen? P. Stute 2 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Das äussere weibliche Genital 12: Preputium clitoridis 9: Vestibulum vaginae 2: Labia majora 8: Labia minora P. Stute 3 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Schwellkörper(muskeln) der Frau 17: Corpus clitoridis 18: Glans clitoridis 7: M. bulbospongiosus 20: M. ischiocavernosus P. Stute 16: Crus clitoridis 13: Urethra 6: Bulbus vestibuli (Schwellkörper) 4 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Schwellkörper Klitoriskörper Glans Klitorisschenkel (Corpus cavernosum dextrum) P. Stute Klitorisschenkel (Corpus cavernosum sinistrum) 5 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern „Cluster erektiler Gewebe“ bei der Frau • Klitoris • Bulbus vestibuli • Labia minora • Corpus spongiosum der Urethra Kontrovers: G-Punkt Kontrovers: vaginaler Orgasmus. P. Stute Puppo V. Clinical Anatomy 2013 Jannini EA et al., J Sex Med 2012 6 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Sexualreflex der Frau Lendenmark Sakralmark P. Stute 7 reasons, sexual intercourse may become uncomfortable. However, these physiological alterations are only related to the reproductive (i.e., internal) organs of women because estrogen does not affect the clito- Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Rhythmische Kontraktionen von ... Chiarugi and Bucc, cervix; cl, clitoe; cu, carina urePawlik’s triangle. he thin epithelial nd the vestibule. and of the vestithe urethral orient of orgasm in an clitoral stimuimulation of the he whole female 1: M. bulbo- 3: M. levator ani types spongiosus of female lly in terms of by Masters and is responds with and psychogenic and Fortenberry 4: M. sphincter ically considered ani externus , orgasms occureen occasionally 8) revealed that P. Stute 2: M. ischiocavernosus M. transv. perinei prof. et. superfic. Puppo V. Clinical Anatomy 2013 Fig. 21. Perineal muscle contractions to the orgasm and the female emission (from Puppo, 2011d). 1, 8 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Meston CM & Frohlich PF. The neurobiology of sexual function. Arch Gen Psychiatry 2000. Klitorale Schwellung Sexuelle Stimulation NO Produktion in Nerven und Gefässen der Klitoris NO aktiviert GTP GTP > cGMP cGMP relaxiert glatte Muskulatur in Schwellkörper und Arteriolen Inhibitor z.B. Sildenafil cGMP > GMP (Phosphodiesterase (PDE) Typ 5 Blutstau in Klitoris P. Stute 9 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern PDE5-Hemmer bei Frauen Fazit: objektiv positiv, aber subjektiv inkonsistente Ergebnisse. P. Stute 10 Anatomie und Funktion der weiblichen Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Neuro-Hormon-Chemie des Orgasmus Hormonachse: HypothalamusHypophyse-Ovar Hy Gehirn Hirnanhangsdrüse (Hypophyse) Vorderlappen Wechselwirkung Freisetzung von Östrogen und Progesteron und Rückkoppelung Freisetzung von Gonadotropinen (FSH, LH) P. Stute 11 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Serotonin und Dopamin Neurotransmitter NT-Level (NT) Sexuelle Kohorte / Charakteristika Funktion Serotonin • Erregung é ê MAO-Hemmer, SSRI • Orgasmus é ê MAO-Hemmer, SSRI é é Antidepressiva + Cyproheptadin (reduziert 5HT-2-Rez. Aktivität) Dopamin • Libido é é Levodopa/Carbidopa (M. Parkinson) • Erregung - - - • Orgasmus é ê Antipsychotika Meston CM & Frohlich PF. The neurobiology of sexual function. Arch Gen Psychiatry 2000. P. Stute 12 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Adrenalin und Noradrenalin Neurotransmitter NT-Level (NT) Sexuelle Kohorte / Charakteristika Funktion Adrenalin • Libido é é Frauen ohne FSD • Erregung é é Frauen ohne FSD é ê Erhöhter Sympathikotonus + FSD é é Frauen ohne FSD ê ê Antipsychotika • Libido é Yohimbin bei HSDD • Erregung é é Frauen ohne FSD • Orgasmus é é Frauen ohne FSD • Orgasmus Noradrenalin Meston CM & Frohlich PF. The neurobiology of sexual function. Arch Gen Psychiatry 2000. P. Stute 13 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern ACH, Histamin und Opioide Neurotransmitter NT-Level (NT) Sexuelle Kohorte / Charakteristika Funktion Acetylcholin • Erregung ê " Atropin bei Frauen ohne FSD • Orgasmus ê " Atropin bei Frauen ohne FSD ê ê Cimetidin (Fallstudie) é êé Langzeit-Opiode (z.B. Heroin) ê é Naloxon • Erregung ê " Naloxon • Orgasmus é ê Langzeit-Opiode (z.B. Heroin) Histamin • Libido Opioide • Libido Meston CM & Frohlich PF. The neurobiology of sexual function. Arch Gen Psychiatry 2000. P. Stute 14 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Fazit: Neurotransmitter Serotonin (5HT-2-Rez.) P. Stute Dopamin (D2 und D4-Rez.) (Nor-)Adrenalin 15 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern P. Stute 16 Der weibliche Hormonhaushalt – schematische Darstellung Abteilung für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Achsen HypothalamusHypophysePeripherieAchsen 1. Ebene Hormondrüse 2. Ebene Hormon Vasopressin Hormondrüse Hormon a TRH Thyroideastimulierendes Hormon (TSH) b PRH (Dopamin) Prolactin * GHRH Wachstumshormon (HGH / STH) Schilddrüse Leber Hypophyse Adrenokortikotropes Hormon Nebennierenrinde (ACTH) CRH Follikelstimmulierendes Hormon (FSH) e GnRH Eierstöcke P. Stute Epiphyse Zirbeldrüse Thyroxin (T4) IGF - 1 (insulin-like growth factors) Glukokortikoide (Cortisol) Sexualhormone (Oestrogene, Gestagene, Androgene) Oestrogene Luteinisierungshormon (LH) f Trijodthyronin (T3) Mineralokortikoide (Aldosteron) Vorderlappen d Hormon Vasopressin (Antidiuretisches Hinterlappen Hormon - ADH) (Speicherung) Oxytocin Hypothalamus Hormondrüse Periphere Organe Hypophyse Oxytocin c 3. Ebene Gestagene Androgene Melatonin Nebenschilddrüsen Parathormon 17 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Androgene Hormon Hormon Sexuelle Kohorte / Charakteristika i.S. Funktion é é Natürliche Menopause é é Operative Menopause é é GV-Frequenz (keine FSD) é é GV-Initiierung bei Adoleszentinnen é é Masturbation-Frequenz (keine FSD) ê ê Ovarektomie; Adrenalektomie ê ê Transsexualität Mann > Frau é é Objektiv: Vaginale Durchblutung é é Subjektiv: DHEA postmenopausal é Subjektiv: DHEA prämenopausal Testosteron • Libido • Erregung P. Stute 18 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Östrogen und Progesteron Hormon Hormon Sexuelle Kohorte / Charakteristika i.S. Funktion é é Frauen ohne FSD é Menopause éê Frauen mit vs. ohne HSDD ê ê Menopause é é HRT é ê Progesteronimplantat é éê Hormonale Kontrazeptiva é " Prämenopause Progesterontherapie é Postmenopause Progesterontherapie Östrogen • Libido • Erregung Progesteron • Libido P. Stute 19 Der weibliche Hormonhaushalt – schematische Darstellung Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Achsen HypothalamusHypophysePeripherieAchsen 1. Ebene Hormondrüse 2. Ebene Hormon Vasopressin Hormondrüse Hormon a TRH Thyroideastimulierendes Hormon (TSH) b PRH (Dopamin) Prolactin * GHRH Wachstumshormon (HGH / STH) Schilddrüse Leber Hypophyse Adrenokortikotropes Hormon Nebennierenrinde (ACTH) CRH Follikelstimmulierendes Hormon (FSH) e GnRH Eierstöcke P. Stute Epiphyse Zirbeldrüse Thyroxin (T4) IGF - 1 (insulin-like growth factors) Glukokortikoide (Cortisol) Sexualhormone (Oestrogene, Gestagene, Androgene) Oestrogene Luteinisierungshormon (LH) f Trijodthyronin (T3) Mineralokortikoide (Aldosteron) Vorderlappen d Hormon Vasopressin (Antidiuretisches Hinterlappen Hormon - ADH) (Speicherung) Oxytocin Hypothalamus Hormondrüse Periphere Organe Hypophyse Oxytocin c 3. Ebene Gestagene Androgene Melatonin Nebenschilddrüsen Parathormon 20 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Cortisol Hormon Hormon Sexuelle Kohorte / Charakteristika i.S. Funktion • Libido é ê Cushing Syndrom • Erregung é Frauen ohne FSD • Orgasmus é Frauen ohne FSD Cortisol Der negative Effekt von Cortisol ist whs. eher indirekt auf eine begleitende Depression als auf einen direkten Einfluss zurückzuführen. Meston CM & Frohlich PF. The neurobiology of sexual function. Arch Gen Psychiatry 2000. P. Stute 21 Der weibliche Hormonhaushalt – schematische Darstellung Abteilung für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Achsen HypothalamusHypophysePeripherieAchsen 1. Ebene Hormondrüse 2. Ebene Hormon Vasopressin Hormondrüse Hormon a TRH Thyroideastimulierendes Hormon (TSH) b PRH (Dopamin) Prolactin * GHRH Wachstumshormon (HGH / STH) Schilddrüse Leber Hypophyse Adrenokortikotropes Hormon Nebennierenrinde (ACTH) CRH Follikelstimmulierendes Hormon (FSH) e GnRH Eierstöcke P. Stute Epiphyse Zirbeldrüse Thyroxin (T4) IGF - 1 (insulin-like growth factors) Glukokortikoide (Cortisol) Sexualhormone (Oestrogene, Gestagene, Androgene) Oestrogene Luteinisierungshormon (LH) f Trijodthyronin (T3) Mineralokortikoide (Aldosteron) Vorderlappen d Hormon Vasopressin (Antidiuretisches Hinterlappen Hormon - ADH) (Speicherung) Oxytocin Hypothalamus Hormondrüse Periphere Organe Hypophyse Oxytocin c 3. Ebene Gestagene Androgene Melatonin Nebenschilddrüsen Parathormon 22 Abteilung für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Oxytocin Hypothalamische oxytocinerge Neurone • Neurohypophyse > Blutbahn • Adenohypophyse > Modulation der ACTH Sekretion • Synapse zu anderen Neuronen (Hirnstamm und Rückenmark) > Modulation der Exzitabilität anderer Neurone Stimulation der Sekretion • Mamillenstimulation > Milchsekretion (z.B. Laktation) • Genitale Manipulation > Uteruskontraktion (z.B. postpartal) P. Stute 23 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Oxytocin Hormon Hormon Sexuelle Kohorte / Charakteristika i.S. Funktion • Libido é é Laktation • Erregung é é Frauen ohne FSD é é Laktation é é Frauen ohne FSD é é Orgasmus Intensität Oxytocin • Orgasmus Meston CM & Frohlich PF. The neurobiology of sexual function. Arch Gen Psychiatry 2000. P. Stute 24 Der weibliche Hormonhaushalt – schematische Darstellung Abteilung für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Achsen HypothalamusHypophysePeripherieAchsen 1. Ebene Hormondrüse 2. Ebene Hormon Vasopressin Hormondrüse Hormon a TRH Thyroideastimulierendes Hormon (TSH) b PRH (Dopamin) Prolactin * GHRH Wachstumshormon (HGH / STH) Schilddrüse Leber Hypophyse Adrenokortikotropes Hormon Nebennierenrinde (ACTH) CRH Follikelstimmulierendes Hormon (FSH) e GnRH Eierstöcke P. Stute Epiphyse Zirbeldrüse Thyroxin (T4) IGF - 1 (insulin-like growth factors) Glukokortikoide (Cortisol) Sexualhormone (Oestrogene, Gestagene, Androgene) Oestrogene Luteinisierungshormon (LH) f Trijodthyronin (T3) Mineralokortikoide (Aldosteron) Vorderlappen d Hormon Vasopressin (Antidiuretisches Hinterlappen Hormon - ADH) (Speicherung) Oxytocin Hypothalamus Hormondrüse Periphere Organe Hypophyse Oxytocin c 3. Ebene Gestagene Androgene Melatonin Nebenschilddrüsen Parathormon 25 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Prolaktin Hormon Hormon Sexuelle Kohorte / Charakteristika i.S. Funktion é ê Hyperprolaktinämie é ê Sex. Aktivität bei Hyperprolaktinämie é ê Laktation ê é Dopaminagonist bei Hyper-PRL é é Nach Orgasmus bei Frauen ohne Prolaktin • Libido • Orgasmus FSD P. Stute 26 Abteilung für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Grundzustand = permanente hypothalamische Unterdrückung der hypophysären PRL Sekretion PIF = PRL inhibiting factor Dopamin GABA, Somatostatin, Calcitonin PRF = PRL releasing factor TRH, Oxytocin, VIP AVP, Histidin-Isoleucin-Peptid (Stress) Melmed, Williams Textbook of Endocrinology, 12th edition 2011 P. Stute 27 Abteilung für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Fazit: Hormone Cortisol Prolaktin P. Stute Androgene Oxytocin (Östrogene) 28 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Sexuelle Störungen bei der Frau Der Begriff „Sexuelle Störungen der Frau“ (FSD) umschließt 4 Einzelstörungen, die mit Leidensdruck verbunden sind. Störungen des sexuellen Verlangens Vermindertes sexuelles Verlangen, sexuelle Aversion Störungen der sexuellen Erregung Störungen der Orgasmusfähigkeit Störungen mit sexuell bedingten Schmerzen Dyspareunie, Vaginismus P. Stute 29 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern DSM-IV/V Kriterien der weiblichen Orgasmusstörung (FOD) 1) Persistent or recurrent delay in, or absence of, orgasm following a normal sexual excitement phase. Women exhibit wide variability in the type of intensity of stimulation that triggers orgasm. The diagnosis of Female Orgasmic Disorder should be based on the clinician‘s judgement that the woman‘s orgasmic capacity is less than would be reasonable for her age, sexual experience, and the adequacy of sexual stimulation she receives. 2) The disturbance causes marked distress or interpersonal difficulty. 3) The orgasmic dysfunction is not better accounted for by another Axis I disorder (except another sexual dysfunction) and is not due exclusively to the direct physiological effects of a substance (e.g. a drug of abuse, a medication) or a general medical condition. P. Stute 30 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern 260 FOD Prävalenz Table 3 Prevalence of orgasm problems in selected epidemiological studies Study N of women Country Bancroft et al. (2003b) 987; all in heterosexual relationships United States Age Method of assessment 20–65 Computer-assisted telephone interviewing Time period Prevalence Previous month Orgasm during sexual activity with partner (% of occasions) None: 9.7% \25: 11.4% 25–50: 23.1% 51–75: 20.1% [75: 35.7% Laumann et al. (1999) 1,749; all sexually active over last 12 United months States 18–59 Face-to-face interview Several months or more during past 12 months Unable to experience orgasm: 25.7% Lindal and Stefansson (1993) 421 Iceland 55–57 Face-to-face interview; Diagnostic Interview Schedule (DIS-III-A) Lifetime prevalence Inhibited orgasm (DSM-III criteria): 3.5% Lindau et al. (2007) 479 United States 57–85 Face-to-face interview and self-report questionnaire Several months or more during past 12 months Unable to experience orgasm: 34% Mercer et al. (2003) 4,826; all had at least 1 heterosexual Britain partner in last 12 months 16–44 Computer-assisted self-interview Past 12 months Unable to experience orgasm: Lasted at least 1 month: 14.4% Lasted at least 6 months: 3.7% Najman, Dunne, Boyle, Cook, and Purdie (2003) 908 Australia 18–59 Telephone interview Oberg et al. (2004) 1,056, all sexually active during last Sweden 12 months Richters et al. (2003) 9,134 18–65 Structured face-to-face interview ? questionnaires Several months in the past 12 months Trouble reaching orgasm: 21–30% (depending on age) Past 12 months Difficulties reaching orgasm: Manifest: 22%; Mild: 60% Australia 16–59 Computer-assisted telephone interview At least 1 month in the past Unable to experience orgasm: 28.6% 12 months aber nur ca. 5% dadurch „gestresst“! Spira, Bajos, and The ACSF 1,137 Group (1994) France 18–69 Telephone interview Lifetime Unable to experience orgasm: Ventegodt (1998) Denmark 18–88 Postal questionnaire Current experience Unable to experience orgasm: 6.8% Finland Past month Problems with orgasm (met FSFI cut-off score of 3.75): 31%; Often: 11% Sometimes: 21% (Shifren Witting et al. (2008) et al. 5,4632008) 18–49 Questionnaires (FSFI ? FSDS) Graham CA. Arch Sex Behav 2010 Met FSFI cut-off and reported distress: 16% Note: manifest = ‘‘quite often’’, ‘‘nearly all the time’’, and ‘‘all the time’’; mild = ‘‘hardly ever’’ and ‘‘quite rarely’’ FSFI Female Sexual Function Index (Rosen et al., 2000), FSDS Female Sexual Distress Scale (Derogatis et al., 2002) P. Stute 31 Arch Sex Behav (2010) 3 753 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Diagnostik der sexuellen Funktionsstörung Sexualanamnese • Aktuelle Beschwerden • Sex. Verhalten • Sex. Beziehung • Kurze sex.- und Beziehungsbiographie Allgemeinmedizinische Anamnese • Systemanamnese • CVD, DM, Psyche, Haut • Medikamente Gynäkologische Anamnese • Zyklus, OP • Kontrazeption, HT Hormonanalysen • FSH • Östradiol • Prolaktin • TSH, T3 / T4 • Androgene Gesamttestosteron SHBG (freies Testo, DHEAS) Körperliche Untersuchung • Gewicht, Blutdruck, • Behaarung ggf. Fragebögen • FSFI (21 items) • B-PFSF (7 items) Gynäkologische Untersuchung • Vulva und Vagina Veränderungen • Inneres Genitale Bildgebung • US Modifiziert nach J. Bitzer, UniMed 2008 P. Stute 32 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Orgasmusstörung Basisdiagnostik Primär Sekundär Psychosoziale Ursachen Sexualhormonmangel Einzeltherapie Paartherapie Vulvovaginale Atrophie Klimakterische Beschwerden Systemische oder lokale HT Östrogen Testosteron P. Stute gesundheitl. u/o sexuelle Probleme des Partners Prädisponierende klinische Faktoren Therapie klinisch relevanter Erkrankungen: Depression Angststörung chronische, hormonelle, metabolische Erkrankungen Medikation FSD Education Team, Cimacteric 2009 33 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Medikamentöse Therapie der weiblichen Orgasmusstörung • Keine Zulassung! P. Stute 34 Bupropion SR, 150 mg PO BID Randomized controlled trial in which women with major Changes in Sexual Functioning depressive disorder who experienced SSRI-associated Questionnaire (CSFQ), orgasm Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern scale sexual dysfunction (n = 42) were treated with completion bupropion SR or placebo for 4 weeks Bupropion, 150 mg PO daily or Single-blind sequential treatment of 20 and 10 Satisfaction with intensity of orgasm 300 mg PO daily non-depressed women and men, respectively, with orgasmic delay or inhibition with placebo, bupropion SR 150 mg/day, and bupropion SR 300 mg/day Bupropion, 150 mg, 300 mg or Randomized placebo-controlled trial of premenopausal CSFQ, orgasm completion scale 400 mg PO daily women with hypoactive sexual desire disorder treated with escalating doses of bupropion (150, 300, or 400 mg/day) (n = 31) vs. placebo (n = 35) Bupropion SR, 150 mg PO daily 30 adults (both men and women) who had received Arizona sexual experience (sexual SSRIs for at least 6 weeks were currently euthymic, dysfunction determined by score and who had sexual dysfunction were randomly greater than 19/30) assigned to receive 150 mg/day of bupropion SR or placebo for 3 weeks Estradiol, 0.014 mg/day transdermal Randomized controlled trial in which postmenopausal Medical Outcomes Study Sexual patch women aged 60–80 years (n = 417) were treated with Problems Index “Orgasm placebo (n = 209) or a 0.014 mg/day transdermal frequency and quality” measure estradiol patch (n = 208) for 24 months Conjugated equine estrogens, 57 hysterectomized women were randomized to receive Personal interviews for sexual 0.625 mg PO or 0.0625 mg/1 g either oral (0.625 mg of conjugated equine estrogens symptoms using a validated Table 1 Continued vaginal cream daily per tablet; n = 27) or topical (0.625 mg conjugated questionnaire before and 3 equine estrogens per 1 g vaginal cream; n = 30) months after estrogen therapy Treatment Study description Measures estrogen administered once daily Estradiol (women with surgical Randomized controlled trial in which healthy FSFI orgasm domain menopause), 0.625 mg/day or postmenopausal women (n = 169) were divided into a estradiol 1 mg/day + drospirenone control group (n = 58), surgically induced menopausal 2 mg/day or Tibolone 2 mg/day women were treated with oral estradiol (n = 23), and natural menopausal women were treated with oral estradiol + drospirenone (n = 22), oral tibolone (n = 42), or vaginal estradiol (n = 24) for 6 months Estradiol 0.1 mg patch daily or Randomized controlled trial in which pharmacologically Derogatis Interview for Sexual progesterone 200 mg suppository induced hypogonadic females with resultant decreased Functioning (DISF) orgasm BID quality of orgasm who were otherwise healthy (n = 20) subscale were treated with estradiol and progesterone for 5 weeks each Ethinylestradiol 15 mg PO daily and Prospective trial in which 48 healthy females were Personal Experiences Questionnaire Gestodene 60 mg PO daily treated with a low-dose oral contraceptive containing (PEQ) orgasm item 15 mg ethinylestradiol and 60 mg gestodene and assessed at 3, 6, and 9 months of use Gingko biloba extract 68 women with sexual arousal disorder were randomized Subjective and physiological to placebo, gingko biloba extract, sex therapy, or sex (vaginal photoplethysmography) therapy plus gingko biloba extract measures of sexual function No significant improvement with bupropion SR 150 mg BID vs. placebo at week 2 or week 4 Significant improvement in satisfaction with intensity of orgasm in females at 150 mg/day (P < 0.05) but not 300 mg/day (P = 0.10) Medikamentöse Therapie der weiblichen Orgasmusstörung Östrogene Fazit: z.T. positiver Effekt, z.T. kein Effekt Methyltestosterone 2 mg PO daily +/- Conjugated estrogens 0.625 mg PO daily and medroxyprogesterone acetate 2.5 mg PO daily P. Stute Randomized controlled trial in which women with postmenopausal sexual complaints(n = 60) were treated with estrogen + progesterone hormone replacement + placebo (n = 29) or hormone replacement + methyltestosterone (2 mg/day) (n = 31) Sexual Energy Change Scale, monthly orgasm frequency diary Significant improvement in orgasm completion (P = 0.0057) at days 28, 56, 84, and 112 as compared to placebo There were no significant differences between the bupropion SR and placebo groups No significant improvement in estradiol group vs. placebo at any time point Anorgasmia decreased significantly in both groups (P < 0.05) Results All hormonal treatments reported to improve orgasm domain scores (P reported as “0.000”), with oral tibolone achieving the highest improvement Neither estradiol (0.1 mg patch/day) or progesterone (200 mg suppository BID) significantly improved orgasm subscale scores No significant change in score at any time period Ginkgo biloba extract combined with sex therapy produced a significant increase in sexual desire and contentment beyond placebo alone. No difference between placebo and ginkgo biloba extract alone. Sex therapy alone enhanced orgasm function when compared with placebo Conjugated estrogens (0.625 mg/ day) + medroxyprogesterone acetate2010 (2.5 mg/day) Ishak et al., J Sex Med increased orgasm frequency (P < 0.001), but methyltestosterone did not significantly improve orgasm frequency beyond hormone replacement 35 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Nijland et al., J Sex Med. 2008 Cayan et al., J Sex Med. 2008 Osmanağaoğlu et al., Climacteric 2006 Tibolon und HRT Sexuelle Funktion in der Postmenopause n Intervention 403 • Tibolon (Livial®) • 50 mcg E2+140 mcg NETA patch (z.B. Estalis®) 3 HRT = Tibolon • Zunahme sex. Fukntion • Zunahme sex. Kontakte • Abnahme Leidensdruck 169 • • • • • 6 Sex. Funktion: ê * Kontrolle é * Hormontherapie Tibolon: v.a. Orgasmus Östrogene: v.a. Lubrikation, Erregung 158 • Tibolon (Livial®) • 2 mg E2+2 mg DNG 6 Sex. Funktion: Tibolon > orale HRT Dyspareunie: Tibolon = orale HRT orales E2 (HE+OVX) E2+DRSP (Angeliq®) Tibolon (Livial®) vaginales E2 (Vagifem®) Kontrolle (z.B. Lafamme) • Kontrolle P. Stute Dauer [Mo] Ergebnis 36 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Medikamentöse Therapie der weiblichen Orgasmusstörung Androgene • Oral – 10 Studien, max. 10 Monate, n = 8-218 post- > prämenopausale Frauen, Methyltestosteron und Testosteronundecanoat • Intramuskulär – 5 Studien, max. 2 Jahre, n = 17-53 postmenopausale Frauen, Testosteron s.c. und i.m. • Transdermal – 13 Studien, max. 1 Jahr, n = max. 562 post- > prämenopausale Frauen, natürliche und chirurgische Menopause, Testosteron patch > Gel, Creme, Spray Woodis CB et al., Pharmacotherapy 2012 P. Stute 37 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Androgentherapie in der Postmenopause • Transdermales Testosteron (300 µg/Tag) erhöht bei postmenopausalen Frauen (OVX und spontan) die monatliche Anzahl befriedigender sexueller Kontakte. LoE A • In den gleichen Studien wurde eine signifikante Zunahme der Libido, Erregbarkeit, Reaktivität (responsiveness), Orgasmusfähigkeit und Zufriedenheit beobachtet. LoE A • Orales DHEA (50 mg/Tag) steigert nicht signifikant die sexuelle Funktion bei postmenopausalen Frauen ohne Östrogenersatz mit HSDD. LoE A Santen RJ et al., THE JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 2010 P. Stute 38 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Androgentherapie in der Prämenopause • Testosteron-Creme (10mg/Tag): erfolgreich. Goldstat R et al., Menopause 2003 • Testosteron-Spray (50-90µg/Tag): erfolgreich. Davis S et al., Ann Intern Med 2008 • Testosteronpropionat 2 mg bei Bedarf: nicht erfolgreich. Apperloo M et al., J Sex Med 2008 Woodis CB et al., Pharmacotherapy 2012 P. Stute 39 für Gynäkologischetreatments Endokrinologie Reproduktionsmedizin, Table 1Abt.Pharmacological forund disorders of orgasm in Frauenklinik women Inselspital Bern Treatment Study description Measures Results Alprostadil, 400 mg vaginal cream prior to intercourse Randomized controlled trial in which 51 women with FSAD were treated for 6 weeks with placebo or alprostadil. Results were analyzed for women who used at least six doses (n = 25) Frequency of orgasm and score changes from baseline using Female Sexual Function Index (FSFI) and Female Sexual Distress Scale (FSDS) (secondary measures) Diary rating orgasm frequency and quality, Interview Rating of Sexual Function Achievement of orgasm increased significantly (P = 0.026) Measures Self-report Frequency of orgasm and score changes from baseline using Female Sexual Function Index (FSFI) and Female Sexual Distress Scale (FSDS) (secondary measures) FSFI, sexual events, Diary total ratingnumber orgasmoffrequency and total number of orgasms, personal quality, Interview Rating of Sexual distress, Functionand adverse drug effects Results 73.5% of ArginMax group reported improved satisfaction in life compared with 37.2% Achievement of overall orgasmsex increased significantly of(Pplacebo = 0.026)group (P < 0.01). Other noted improvements were in sexual desire, reduction of vaginal dryness, frequency of sexual intercourse, orgasm, and clitoral sensation. No significant side effects noted Pretreatment orgasm nor scores: treatment group orgasm 4.3, Neither amantadine buspirone improved control group 4.2. Post-treatment measures compared to placebo scores: treatment group 5.3 (P = 0.01), control group 4.4 (P = 0.1). Treatment group reported greater intercourse satisfaction (P = 0.001) more drug-related 73.5% of ArginMax groupand reported improved adverse effects; 5% (2 sex subjects) had to discontinue satisfaction in overall life compared with 37.2% therapy of placebo group (P < 0.01). Other noted No improvements significant improvement with bupropion SR were in sexual desire, reduction of 150 mg BID vs. placebo at week 2 or week 4 vaginal dryness, frequency of sexual intercourse, Medikamentöse Therapie der weiblichen Orgasmusstörung Amantadine, buspirone Randomized controlled trial in which women with fluoxetine-induced sexualof dysfunction treated with Table 1 Pharmacological treatments for disorders orgasmwere in women amantadine (n = 18), buspirone (n = 19), or placebo (n = description 20) for 8 weeks Treatment Study ArginMax (proprietary nutritional Randomized controlled trial in which 77 women with supplement interest in improving treated Alprostadil, 400containing mg vaginalginseng, cream Randomized controlled sexual trial in function which 51were women withfor 4 ginkgo, damiana, L-arginine, weeks were with ArginMax prior to intercourse FSAD treated foror6placebo weeks with placebo or multivitamins, and minerals) alprostadil. Results were analyzed for women who used at least six doses (n = 25) Psychopharmaka Ishak et al., J Sex Med 2010 Neither amantadine nor buspirone improved orgasm measures compared to placebo Buspiron (Angststörung): Agonist an 5-HT1A-Rezeptoren, Antagonist an D2-Rezeptoren. Amantadin (Influenza-A-Grippe, Parkinson Syndrom): u.a. Dopamin Agonist Bremelanotide, 20 mg intranasal Amantadine, buspirone spray 45–60 minutes prior to attempted intercourse ArginMax (proprietary nutritional supplement containing ginseng, ginkgo, damiana, L-arginine, Bupropion SR, 150 PO BID multivitamins, andmg minerals) 80 married, menstruating women (mean age with 31 years) Randomized controlled trial in which women with female sexual sexual arousaldysfunction disorder were treated with fluoxetine-induced were treated with placebo or intranasal bremelanotide 45–60 minutes amantadine (n = 18), buspirone (n = 19), or placebo prior to attempted intercourse (n = 20) for 8 weeks Randomized controlled trial in which 77 women with interest in improving sexual function were treated for 4 weeks with ArginMax or placebo Randomized controlled trial in which women with major depressive disorder who experienced SSRI-associated sexual dysfunction (n = 42) were treated with bupropion SR or placebo for 4 weeks Single-blind sequential treatment of 20 and 10 80 married, menstruating women (mean age 31 years) non-depressed women and men, respectively, with with female sexual arousal disorder were treated with orgasmic delay or inhibition with placebo, bupropion placebo or intranasal bremelanotide 45–60 minutes SR 150 mg/day, and bupropion SR 300 mg/day prior to attempted intercourse Randomized placebo-controlled trial of premenopausal women with hypoactive sexual desire disorder treated with escalating doses of bupropion (150, 300, or 400 mg/day) (n = 31) vs. placebo (n = 35) Randomized controlled trial in which women with major 30 adults (both men and women) who had received depressive disorder who experienced SSRI-associated SSRIs for at least 6 weeks were currently euthymic, sexual dysfunction (n = 42) were treated with and who had sexual dysfunction were randomly bupropion SR or placebo for 4 weeks assigned to receive 150 mg/day of bupropion SR or Single-blind sequential placebo for 3 weeks treatment of 20 and 10 non-depressed women and with Randomized controlled trial in men, whichrespectively, postmenopausal orgasmic delay or inhibition with placebo, bupropion women aged 60–80 years (n = 417) were treated with SR 150 mg/day, SR 300 mg/day placebo (n = 209)and or abupropion 0.014 mg/day transdermal Randomized placebo-controlled trial of premenopausal estradiol patch (n = 208) for 24 months with hypoactive sexual disorder treated 57women hysterectomized women were desire randomized to receive with escalating doses of bupropion (150, 300, or either oral (0.625 mg of conjugated equine estrogens 400 mg/day) = 31) vs. placebo = 35) per tablet; n =(n27) or topical (0.625(nmg conjugated 30 adults (both men and women) who had received Self-report Bupropion (Depression): Dopamin-, Noradrenalin-, Serotonin-Reuptake-Hemmer Bupropion, 150 mg PO daily or Bremelanotide, 20 mg intranasal 300 mg PO daily spray 45–60 minutes prior to attempted intercourse Bupropion, 150 mg, 300 mg or 400 mg PO daily Bupropion SR, 150 mg PO BID Bupropion SR, 150 mg PO daily Bupropion, 150 mg PO daily or 300 mg PO daily Estradiol, 0.014 mg/day transdermal Changes in Sexual Functioning Questionnaire (CSFQ), orgasm completion scale Satisfaction with intensity of orgasm FSFI, total number of sexual events, total number of orgasms, personal distress, and adverse drug effects CSFQ, orgasm completion scale Changes in Sexual Functioning Arizona sexual experience (sexual Questionnaire (CSFQ), orgasm dysfunction determined by score completion scale greater than 19/30) Satisfaction with intensity of orgasm orgasm, and clitoral sensation. No significant side effects noted Significant improvement in satisfaction with intensity Pretreatment orgasm scores: treatment group 4.3, of orgasm in females at 150 mg/day (P < 0.05) but control group 4.2. Post-treatment scores: treatment not 300 mg/day (P = 0.10) group 5.3 (P = 0.01), control group 4.4 (P = 0.1). Treatment group reported greater intercourse Significant improvement in orgasm completion satisfaction (P = 0.001) and more drug-related (P = 0.0057) at days 28, 56, 84, and 112 as adverse effects; 5% (2 subjects) had to discontinue compared to placebo therapy No significant improvement with bupropion SR There were no significant differences between the 150 mg BID vs. placebo at week 2 or week 4 bupropion SR and placebo groups Significant improvement in satisfaction with intensity orgasm in females at 150 mg/daygroup (P < 0.05) No of significant improvement in estradiol vs. but not 300 mg/day (P = 0.10) placebo at any time point Fazit: positiver Effekt, wenn keine SSRI parallel kein Effekt, wenn SSRI parallel patch Bupropion, 150 mg, 300 mg or 400 mg POequine daily estrogens, Conjugated 0.625 mg PO or 0.0625 mg/1 g vaginalP.cream Stutedaily Bupropion SR, 150 mg PO daily Medical Outcomes Study Sexual Problems Index “Orgasm frequency and quality” measure CSFQ, orgasm completion scale Personal interviews for sexual symptoms using a validated questionnaire before and 3 Arizona sexual experience (sexual Significant improvement in orgasm completion (P = 0.0057) at days significantly 28, 56, 84, and 112groups as Anorgasmia decreased in both compared to placebo (P < 0.05) 40 There were no significant differences between the Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Medikamentöse Therapie der weiblichen Orgasmusstörung Table 1 Pharmacological treatments for disorders of orgasm in women Treatment Study description Measures Results Alprostadil, 400 mg vaginal cream prior to intercourse Randomized controlled trial in which 51 women with FSAD were treated for 6 weeks with placebo or alprostadil. Results were analyzed for women who used at least six doses (n = 25) Frequency of orgasm and score changes from baseline using Female Sexual Function Index (FSFI) and Female Sexual Distress Scale (FSDS) (secondary measures) Diary rating orgasm frequency and quality, Interview Rating of Sexual Function Achievement of orgasm increased significantly (P = 0.026) Self-report 73.5% of ArginMax group reported improved satisfaction in overall sex life compared with 37.2% of placebo group (P < 0.01). Other noted improvements were in sexual desire, reduction of vaginal dryness, frequency of sexual intercourse, orgasm, and clitoral sensation. No significant side effects noted Pretreatment orgasm scores: treatment group 4.3, control group 4.2. Post-treatment scores: treatment group 5.3 (P = 0.01), control group 4.4 (P = 0.1). Treatment group reported greater intercourse satisfaction (P = 0.001) and more drug-related adverse effects; 5% (2 subjects) had to discontinue therapy No significant improvement with bupropion SR 150 mg BID vs. placebo at week 2 or week 4 Bremelanotid Amantadine, buspirone Randomized controlled trial in which women with fluoxetine-induced sexual dysfunction were treated with amantadine (n = 18), buspirone (n = 19), or placebo (n = 20) for 8 weeks Randomized controlled trial in which 77 women with interest in improving sexual function were treated for 4 weeks with ArginMax or placebo Neither amantadine nor buspirone improved orgasm measures compared to placebo Agonist an Melanocortinrezeptor-1 (Hautbräunung) und Melanocortinrezeptor-4 (u.a. Libido) ArginMax (proprietary nutritional supplement containing ginseng, ginkgo, damiana, L-arginine, multivitamins, and minerals) Bremelanotide, 20 mg intranasal spray 45–60 minutes prior to attempted intercourse 80 married, menstruating women (mean age 31 years) with female sexual arousal disorder were treated with placebo or intranasal bremelanotide 45–60 minutes prior to attempted intercourse FSFI, total number of sexual events, total number of orgasms, personal distress, and adverse drug effects Bupropion SR, 150 mg PO BID Randomized controlled trial in which women with major depressive disorder who experienced SSRI-associated sexual dysfunction (n = 42) were treated with bupropion SR or placebo for 4 weeks Single-blind sequential treatment of 20 and 10 non-depressed women and men, respectively, with orgasmic delay or inhibition with placebo, bupropion SR 150 mg/day, and bupropion SR 300 mg/day Randomized placebo-controlled trial of premenopausal women with hypoactive sexual desire disorder treated with escalating doses of bupropion (150, 300, or 400 mg/day) (n = 31) vs. placebo (n = 35) 30 adults (both men and women) who had received SSRIs for at least 6 weeks were currently euthymic, and who had sexual dysfunction were randomly assigned to receive 150 mg/day of bupropion SR or placebo for 3 weeks Randomized controlled trial in which postmenopausal women aged 60–80 years (n = 417) were treated with placebo (n = 209) or a 0.014 mg/day transdermal estradiol patch (n = 208) for 24 months 57 hysterectomized women were randomized to receive Changes in Sexual Functioning Questionnaire (CSFQ), orgasm completion scale Fazit: positiver Effekt, aber zu viele Nebenwirkungen, Daher (noch) keine Weiterentwicklung. Bupropion, 150 mg PO daily or 300 mg PO daily Bupropion, 150 mg, 300 mg or 400 mg PO daily Bupropion SR, 150 mg PO daily Estradiol, 0.014 mg/day transdermal patch P. Stute Conjugated equine estrogens, Satisfaction with intensity of orgasm Significant improvement in satisfaction with intensity of orgasm in females at 150 mg/day (P < 0.05) but not 300 mg/day (P = 0.10) CSFQ, orgasm completion scale Significant improvement in orgasm completion (P = 0.0057) at days 28, 56, 84, and 112 as compared to placebo Arizona sexual experience (sexual dysfunction determined by score greater than 19/30) There were no significant differences between the bupropion SR and placebo groups Medical Outcomes Study Sexual Problems Index “Orgasm frequency and quality” measure Personal interviews for sexual Ishak improvement et al., J Sex Med group 2010 No significant in estradiol vs. placebo at any time point 41 Anorgasmia decreased significantly in both groups Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Medikamentöse Therapie der weiblichen Orgasmusstörung Ishak et al., J Sex Med 2010 • Mianserin = tetrazyklisches Antidepressivum positiv (15mg/die) bei SSRI induzierter FSD • Gingko biloba extract positiv nur in Verbindung mit Sexualtherapie • Yohimbin = Antagonist an α2-Adrenozeptoren Positiv (12-20mg/die) bei SSRI-induzierter FSD • Zestra = botanisches Massageöl (auf Vulva) positiv (Frauen mit / ohne FSD), wenn Applikation vor GV • Oxytocin Nasenspray ? P. Stute 42 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Fazit - I • Der Orgasmus ist das Ergebnis des Zusammenspiels von – adäquater Stimulation – intakten Genitalorganen inkl. deren Gefässe und Nerven – (Beckenboden-)Muskulatur – Gehirn und Rückenmark – Neurotransmittern und -modulatoren – Hormonen • Die weibliche Orgasmusstörung (FOD) gemäss DSMKriterien ist selten (5%). P. Stute 43 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Fazit - II • Die FOD Therapie ist multidisziplinär. • Es sind keine Medikamente zur Behandlung der FOD zugelassen. • Positive Effekte wurden beschrieben für – – – – – – – – P. Stute z.T. Östrogene (postmenopausal) Testosteron (v.a. postmenopausal) Tibolon (postmenopausal) Bremelanotid (prämenopausal) Bupropion Mianserin und Yohimbin (SSRI-induzierte FSD) Gingko (in Kombination mit Sexualtherapie) Zestra topisch 44 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern DANKE! P. Stute 45 Abt. für Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenklinik Inselspital Bern Orgasmustypen • Online-Befragung von 225 Frauen • Typ I (tiefer Ursprung) – Schwebegefühl (floating sensation) – Apnoe – Selbstverlust (loss of self) – Sucking sensation – Partnercharakteristika: guter Geruch, dominantes und gleichzeitig rücksichtsvolles Verhalten, kraftvolle Penetration (aber nicht Aggressivität, „Muckis“ und Maskulinität) • Typ II (oberflächlicher Ursprung) – eher lokalisiert – entspannender P. Stute King R & Belsky J, Arch Sex Behav 2012 46
