60 Minutes of Sex Drive Becky Kaufman Lynn, MD, MBA, IF, NCMP Evora Women’s Health Adjunct Associate Professor of Obstetrics & Gynecology Saint Louis University

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• Speaker for TherapeuticsMD, AMAG, Viveve, Sprout • Shareholder in TherapeuticsMD, AMAG, Palatin

Disclosures

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Objectives •Prevalence •Assessment •Treatment of low sex drive •Cases

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2 43 45 40 32 35 28 National 30 21 Health 25 and Social 20 Life Survey 15

Percent of Women Reporting 10

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0 Any Sexual Lack of Sexual Unable to Achieve Pain During SexPain Any Sexual Complaint Lack of Interest Unable to Orgasm Achieve with Sex Laumann EO, Paik A, Complaint Interest orgasm Rosen JAMA. 1999;281(6):537 Sexual complaint

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Preside Study

Complaint Problem Distress

Desire 38.7 10%

Arousal 26.1 5.4%

Orgasm 20.5 4.7%

Any Sexual 44.2 12% Complaint

Shifren et al Obstet Gynecol. 2008;112(5):970

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5 + A good sex life adds 10%‐15% more value to a relationship, but a bad sex life negatively impacts a relationship by 50%‐70%

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Sexual Response Cycle (Masters and Johnson/Helen Singer Kaplan)

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Intimacy Based Sexual Response Cycle Emotional Intimacy

Emotional Sexual and Physical Satisfaction Stimuli Spontaneous Sex Drive

Arousal and Arousal Desire

Basson, Obstet Gynec 2001 98: 350‐53 14

7 Neurobiology of Female Sexual Dysfunction

The Journal of Sexual Medicine pages 260‐268, 22 OCT 2007 15

Dual Control Dual Control Model and Sexual Tipping PointModel

Dopamine Endocannabinoids Melanocortins Serotonin

Oxytocin Opioids Norepinephrine Prolactin Pfaus, J. J Sex Med 2009:6 1506‐33 16

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9 Desire

Pain Arousal

Orgasm

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Hypo‐ active Sexual Desire Disorder

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10 What is HSDD? Any of the following for 6 months or more

Lack of motivation for sexual activity manifested by reduced or absent spontaneous desire Reduced or absent responsive desire to erotic cues and stimulation Loss of desire to initiate or participate in sexual activity AND is combined with clinically significant personal distress

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HSDD Onset Context Characteristics

Lifelong Generalized, any Causes situation, any significant partner personal distress Aquired, follows Situational Mild, moderate, a period of severe normal functioning

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11 Why are we not asking about it?

•HCP barriers •Patient barriers •Time Constraints •RVU Constraints

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It’s easy!

Do you have any sexual concerns you would like to discuss?

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Directed H and P

• For how long? • Sexual Assault or Trauma • How long have you been • Does your partner have any together? medical problems? • Are you getting what you • Pain/Vaginal dryness need emotionally? • Difficulty with orgasm • Describe your partner in 4 • Medicines words • What did your parents/family • Depression, Anxiety teach you about sex? • Personal insight • Body Image Is there anything else you think is important that I haven’t asked you?

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13 What Contributes to HSDD?

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History and Physical should be guided by the biopsychosocial model

Physiologic Psychologic

Relational/ Sociocultural Interpersonal

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14 Medicines Associated with Sexual Dysfunction

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15 Reassurance You are not alone

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Nonpharmacologic

Nurture/prioritize your relationship Communicate your needs Love languages Schedule sex/erotic play date

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16 Nonpharmacologic

Adjust modifiable factors Medicines Behaviors Tune up medical problems

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Erotic Reading/ Listening

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17 Pharma

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Hormones •Testosterone

Neurotransmitter Modulators Flibanserin Bremelanotide

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18 Testosterone

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Testosterone Numerous studies suggest that testosterone in post menopausal women improves : Desire Arousal Orgasm frequency Pleasure and sexual responsiveness Davis SR. Global Consensus Position Statement And reduces distress on the Use of Testosterone Therapy for Women. J Clin Endocrinol Metab. 2019 Oct; 104(10): 4660–4666

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19 Recommendations •Can be used to treat HSDD in postmenopausal women who have undergone a biopsychosocial assessment •Goal is to replace testosterone to the normal premenopausal

Davis SR. Global Consensus Position Statement range on the Use of Testosterone Therapy for Women. J Clin Endocrinol Metab. 2019 Oct; 104(10): 4660–4666

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Off label use in: • Menopausal or perimenopausal women on or not on HRT • Do not need to use estrogen and progesterone with it although it tends to work better in the presence of estrogen • Per consensus statement, avoid compounding pharmacies, but noncompounded is expensive and not covered • Women need 1/10 the amount of testosterone of men

Davis SR. Global Consensus Position Statement on the Use of Testosterone Therapy for Women. J Clin Endocrinol Metab. 2019 Oct; 104(10): 4660–4666

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20 • Recommend against oral formulations Testosterone • Recommend against pellets • Topical daily formulations keep a steadier blood level than intramuscular • Testosterone 1% cream 0.5 grams daily to calf

Davis SR. Global Consensus Position Statement on the Use of Testosterone Therapy for Women. J Clin Endocrinol Metab. 2019 Oct; 104(10): 4660–4666

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Testosterone

• No increase in BP, HbA1c • Insufficient data to evaluate cardiovascular risk and most high risk women were excluded from T trials • T does not increase breast density, short term transdermal T does not affect breast cancer risk • Caution is recommended for use in women with hormone receptor positive breast cancer • Insufficient data to show that T improves muscle mass, fatigue, weight loss, cognitive function • Acne, mild facial hair are the most common side effects • Clitoromegaly, deepening of the voice, alopecia occur at high doses and the first 2 are permanent Davis SR. Global Consensus Position Statement on the Use of Testosterone Therapy for Women. J Clin Endocrinol Metab. 2019 Oct; 104(10): 4660–4666

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21 Testosterone

• Check baseline levels, then 3 and 6 months • Monitor for signs of androgen excess with a serum total testosterone level every 6 months, to screen for overuse • If no benefit by 6 months, treatment should be ceased

Davis SR. Global Consensus Position Statement on the Use of Testosterone Therapy for Women. J Clin Endocrinol Metab. 2019 Oct; 104(10): 4660–4666

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• Male range testosterone Hormone • Hair loss • Deepening of the voice Pellets‐ T • Enlarged clitoris • Hemoconcentration

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22 Flibanserin

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• First available treatment for generalized, acquired HSDD in premenopausal women • Acts in the brain on neurotransmitters associated with desire to enhance excitation and decrease inhibitory response to sexual cues • Mixed serotonin agonist and antagonist, and dopamine agonist • Thought to produce region‐ specific elevations in dopamine and norepinephrine to offset inhibitory serotonergic activity

. US FDA. CDER. Flibanserin NDA 022526. Label 5/2018

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23 Flibanserin

Updated Black Box Warning –don’t drink etoh Takes 4‐6 weeks to see a 100 mg at bedtime, daily at least 2 hours before response taking at bedtime, or skip the dose for that evening

Clinicians and pharmacies Also contraindicated with OCP not a contraindication must be certified to moderate to strong CYP‐ (weak CYP‐3A4) but prescribe through the 3A4 inhibitors caution REMS program

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Flibanserin Trials Study 147 Study 7 Study 785 SSE + + + E diary X ‐ ‐ FSFI Desire + + + FSDS‐R13 +++ (distress) FSFI Total +++ Score FSDS‐ Total +++ Score

Katz M, et al. J Sex Med. 2013;10:1807-1815. 2. Fisher WA, et al. Sex Med Rev. 2017;5:445-460. 3. Derogatis LR, et al. J Sex Med. 2012;9:1074‐1085. 4. Thorp J, et al. J Sex Med. 2012;9:793‐804.

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24 Snowdrop Trial

Randomized, double‐blinded, placebo‐controlled trial of flibanserin in postmenopausal women 100 mg taken at bedtime significantly improved sexual desire and sexual function and decreased associated distress

. Simon et al. Menopause. 2014

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• Randomized, double‐blinded, placebo‐controlled trial of flibanserin in postmenopausal women • 100 mg taken at bedtime significantly improved FSFI‐desire score • Dizziness was the most common side effect

JSM 2017

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25 Are SSE a good surrogate for desire?

Not if your child is knocking on the door!

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Bremelanotide

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26 Bremelanotide

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Bremelanotide

• NDICATIONS AND USAGE • Bremelanotide is a melanocortin receptor agonist indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD) and is NOT due to: • A co‐existing medical or psychiatric condition • Problems with the relationship • The effects of a medication or drug substance • Bremelanotide is not indicated for the treatment of HSDD in postmenopausal women or men • Bremelanotide is not indicated to enhance sexual performance

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27 Bremelanotide

• CONTRAINDICATIONS • Contraindicated in patients who have uncontrolled hypertension or known cardiovascular disease. • Transient increase in blood pressure and decrease in heart rate: • Focal hyperpigmentation: Reported by 1% of patients who received up to 8 doses per month • Nausea: Reported by 40% of patients who received up to 8 monthly doses

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• Randomized (1:1) ~1,250 women with HSDD • Subjects self‐administered Bremelanotide or placebo using the auto‐injector as desired 45 minutes in advance of anticipated sexual activity • open‐label 52‐week extension study

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28 Co‐Primary Endpoint: Improvement in Desire Change in FSFI Desire (FSFI‐D) Domain Score from Baseline to End of Core (Double‐Blind) Phase

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Co‐Primary Endpoint: Reduction in Distress Change in FSDS‐DAO Question 13 from Baseline to End of Core (Double‐Blind) Phase

Compared with placebo, women using bremelanotide had a significant reduction in distress as measured by FSDS‐DAO Question 13 score at 6 months

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29 Adverse Events in >4% of Patients

The majority of adverse events were reported as mild (31%) to moderate (40%) and transient Discontinuation rates were 18% in the bremelanotide group vs 2% in the placebo group Discontinuation due to nausea was 8% in the bremelanotide group vs 0% in the placebo group

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Clayton AH, et al. Mayo Clin Proc. 2018;93:467‐487.

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30 Case Presentation

• Charley is a 35 year old mother of 2 kids, age 3 and 4. She had a successful career until she decided to stop working after kids. They just moved here from Portland and she has no family in the area. She has gained about 40 lbs since before her kids. Her husband works long days and is exhausted when he gets home at night. She presents with low libido. What would you do for her?

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The Mommy Syndrome

• No adult time • 2 small children • Weight gain‐ poor body image • Resentment • Depression • Feels bad leaving the children

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31 No adult time Make time for each other

2 small children. Get a babysitter

Weight gain‐ poor body image Exercise, eating plan Red Flags: Resentment The Mommy Communication with partner, counseling Syndrome Depression Confidence building, therapy, ?buproprion

Feels bad leaving the children Get over it! A happy mommy is a better mommy

Consider use of Flibanserin or Bremelanotide

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LULU

• Lulu is a 34 year old woman whose mother and grandmother died of breast cancer. She is found to have the BRCA1 gene. After she has her children, she has a double mastectomy, reconstruction and a hyst/BSO. Her primary OBGYN has put her on an estradiol patch. She presents with complaints of low libido and fatigue.

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32 Red Flags

• Lost testosterone abruptly • Changed body image after mastectomy

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Treatment

• Therapy to work through body image issues • Work on feeling sexy again • Assess for anxiety and depression • Improve communication about the new normal

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33 • Treatment: Testosterone • Goal: normal Treatment • premenopausal range • Flibanserin • Bremelanotide

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Mila

• Mila is 55 year old who presents to your office with low libido. She and her partner have been together for 25 years. On further questioning, she describes vaginal dryness which is causing painful sex. She has tried OTC lubes but they are not working for her. Her PCP prescribed vagifem but she read the package insert and decided not to use it. She is also unable to reach orgasm.

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34 Red Flags

Painful sex

Lack of orgasm

Type of lube

Worried about the risks of hormones

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In order to have sex, it has to be sex worth wanting

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35 Treatment • The usual nonpharmacologic treatments • Make sure to ask about pain • Long term relationship • Silicone based lube • Discuss risks of hormones • Vaginal hormones do not increase the risk of breast cancer, blood clot, heart attack or stroke • Estrogen cream to clitoris • Mindfulness, fantasy • Consider O cream • Consider Viagra • Hormones are the gas that makes the car go

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Sexual health is important to quality of life

HSDD/low sex drive is a highly prevalent To condition that is underrecognized sum Only 1/3 of women seek formal care There are pharmacological and up nonpharmacological treatments We can all empower women to lead healthy sex lives!

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36 @evorawomenshealth

@beckyklynnmd

@beckyklynnmd

THANK @beckyklynn

Search Dr. Becky Lynn

YOU! [email protected]

www.evorawomen.com 226 S. Woods Mill Road, Ste. 46W St. Luke’s Hospital Chesterfield, Mo 63017 314 934 0551

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