Desire Disorder In Premenopausal Women Research Articles

Pharmacotherapy of Hypoactive Sexual Desire Disorder in Premenopausal Women.

This review aims to provide an overview of pharmacologic management for hypoactive sexual desire disorder (HSDD) in premenopausal women, with a focus on available agents. Through a literature search on PubMed, Google Scholar, and ClinicalTrials.gov from 1999 to 2024, studies were selected using the following MeSH search terms: hypoactive sexual desire disorder, premenopause, pharmacologic management, flibanserin, bremelanotide, buspirone, bupropion, and testosterone, excluding those involving postmenopausal women or other sexual disorders. Product monographs were also reviewed. Relevant English-language studies or those conducted in humans were considered. Hypoactive sexual desire disorder, characterized by a lack of motivation for sexual activity, predominantly affects women aged 45 years and older. Treatment involves a multimodal approach, including nonpharmacologic interventions such as psychotherapy and lifestyle adjustments, alongside pharmacologic options. Although bupropion and buspirone may be considered off-label treatments, flibanserin and bremelanotide are the sole medications approved by the Food and Drug Administration for generalized acquired HSDD in premenopausal women. However, caution is advised due to their limited efficacy, potential adverse effects, and transparency issues in reporting. Hypoactive sexual desire disorder, while not life-threatening, significantly impacts well-being and relationships. Pharmacotherapy, including options like flibanserin and bremelanotide, is essential within a multidisciplinary approach. Validated tools and objective measures inform tailored premenopausal HSDD care plans and aid in striking a balance between potential risks and adverse effects while maximizing meaningful clinical benefits, including for transgender individuals. Clinicians must discern important distinctions between flibanserin, bremelanotide, and other agents when managing premenopausal HSDD. Further research with the most suitable clinical endpoints and consideration of patient factors are crucial before widespread adoption of flibanserin and bremelanotide. Pharmacists are encouraged to embrace this opportunity to provide premenopausal HSDD care in ambulatory and community practice settings.

(235) Use of Bremelanotide (Vyleesi) in Men with Sexual Dysfunctions

Abstract Introduction Bremelanotide (Vyleesi) is an FDA approved medication for the safe and efficacious treatment of hypoactive sexual desire disorder in premenopausal women, however phase 3 trials revealed it improved arousal and orgasm as well. As a centrally acting drug it was expected to be effective to treat sexual dysfunctions in men and has been prescribed off label routinely in our practice. Objective The primary aim of this study was to evaluate the use of bremelanotide in men with various sexual dysfunctions, the reasons why the medication was prescribed, improvements in sexual function and overall satisfaction, and side effects experienced. Methods This one-group study design involved men from a single clinic with various sexual dysfunctions prescribed bremelanotide beginning May 1, 2021. After signing consent participants answered the Quality of Life (QOL) Dimension of Sexual Quality of Life Questionnaire, the Patient Global Impression of Improvement (PGI-I) and the General Assessment Questions (GAQ) online. After confirming they had used the medication at least twice, participants completed a structured interview over the telephone with a single interviewer. Descriptive statistics were used to characterize the study cohort. Adverse events were collected. Results To date a total of 21 men signed consent and 19 completed the online questionnaires. 80% of these men were more satisfied with their lovemaking and duration of lovemaking; 93% reported vaginal insertion was easier and 71% said it was easier to orgasm. With regard to feelings about initiating lovemaking, 86% were more at ease and 79% anticipated it would be more pleasurable and more carefree. 69% believed orgasm was more pleasurable and 73% said that lovemaking was more pleasurable while 79% reported that the partner’s overall experience was more pleasurable. Using the PGI-I, 53% of participants felt that sexual function after using bremelanotide was a little better, much better, or very much better. Additional questions online revealed similar results. Twelve men completed the one-on-one interview: 69% of participants were prescribed bremelanotide for erectile dysfunction. 64% had at least other one sexual health issue, including anxiety about sex (54%), low sexual desire (45%), not enjoying sex (36%), orgasm difficulties (18%), and ejaculation difficulties and sensation loss (9% each). A total of 91% experienced improvements in sexual function, all with improved erectile function. 100% of those with complaints of low sexual desire and/or complaints of anxiety around sex reported improvement; 64% had decreased anxiety around sex; 55% had more enjoyment with sex; and orgasm improved for 36% of participants. Men reported longer erection and ability for additional erection for 18-24 hours after bremelanotide injection, better connection between genitals and brain, improved sensitivity, and increased confidence. Side effects included flushing (36%), nausea (36%), headache (27%), bothersome spontaneous erections without sexual stimulation for about 24 hours after injection (27%), and incontinence, cramping and abdominal burning (9% each). All adverse events were transient. Conclusions While bremelanotide is approved for hypoactive sexual desire disorder in premenopausal women, it has been prescribed and used successfully for men with erectile dysfunction and other concomitant sexual health issues. Disclosure Yes, this is sponsored by industry/sponsor: Palatin Technologies. Clarification: Industry funding only - investigator initiated and executed study. Any of the authors act as a consultant, employee or shareholder of an industry for: Palatin Technologies.

Melanocortin receptors in GtoPdb v.2023.1

Melanocortin receptors (provisional nomenclature as recommended by NC-IUPHAR [41]) are activated by members of the melanocortin family (α-MSH, β-MSH and γ-MSH forms; δ form is not found in mammals) and adrenocorticotrophin (ACTH). Endogenous antagonists include agouti and agouti-related protein. ACTH(1-24) was approved by the US FDA as a diagnostic agent for adrenal function test. setmelanotide was approved by the US FDA for weight management in patients with POMC, PCSK1 or LEPR defiency, bremelanotide was approved by the US FDA for generalized hypoactive sexual desire disorder in premenopausal women, and NDP-MSH (afamelanotide) was approved by the EMA for the treatment of erythropoietic protoporphyria. Several synthetic melanocortin receptor agonists are under clinical development.

Accidental Flibanserin Ingestion in Children Causing Acute Respiratory and Central Nervous System Depression: What Health Care Professionals Need to Know.

This commentary serves to raise awareness for health care professionals about the potential risks of accidental ingestion of flibanserin tablets by children. Flibanserin was approved by the U.S. Food and Drug Administration (FDA) for the treatment of acquired generalized hypoactive sexual desire disorder in premenopausal women. Since its approval in 2015, the FDA has identified five reports of serious accidental ingestion by toddlers. All five children, boys with ages ranging from 18 months to 2 years, presented with central nervous system and respiratory depression, and two of them required intubation. A combination of hypertension, hyperthermia, and seizure-like activity was also seen in four of the five children. The clinical manifestation resembles serotonin syndrome (eg, tachycardia, hypertension, and muscle stiffness). As flibanserin use increases, greater awareness by health care professionals regarding the risk of accidental pediatric ingestion is needed to facilitate preventative counseling for patients with young children.

The neurobiology of bremelanotide for the treatment of hypoactive sexual desire disorder in premenopausal women.

Hypoactive sexual desire disorder (HSDD) is a common female sexual dysfunction and is estimated to affect approximately 10% of women in the United States. It has been suggested that HSDD is associated with an imbalance of hormone and neurotransmitter levels in the brain, resulting in decreased excitation, increased inhibition, or a combination of both. Evidence suggests neurotransmitters, including dopamine (DA), norepinephrine, and serotonin, as well as hormones such as estradiol and testosterone, contribute to female sexual desire and response. Current treatments for HSDD include psychotherapy, and two US Food and Drug Administration-approved medications for premenopausal women: flibanserin, a serotonin mixed agonist and antagonist, and bremelanotide, a melanocortin receptor (MCR) agonist. Melanocortins are endogenous neuropeptides associated with the excitatory pathway of the female sexual response system. MCRs are found throughout the body, including the brain. Bremelanotide is an MCR agonist that nonselectively activates several of the receptor subtypes, of which subtype 4 (MC4R) is the most relevant at therapeutic doses. MC4R is predominantly expressed in the medial preoptic area (mPOA) of the hypothalamus in the brain, and is important for female sexual function. Animal studies suggest that bremelanotide may affect female sexual desire by activating presynaptic MC4Rs on neurons in the mPOA of the hypothalamus, leading to increased release of DA, an excitatory neurotransmitter that increases sexual desire. This review presents what is known about the mechanism of action of bremelanotide in the context of treating HSDD.

Optimized Nanostructured Lipid Carriers Integrated into In Situ Nasal Gel for Enhancing Brain Delivery of Flibanserin.

Background and AimFlibanserin (FLB) is a multifunctional serotonergic agent used for treating hypoactive sexual desire disorder in premenopausal women via oral administration. FLB has a reported limited oral bioavailability of 33% that could be attributed to the drug’s first-pass metabolism. In addition, FLB has a pH-dependent solubility that could be a challenging factor for drug dissolution in the body neutral fluid, and consequently, absorption via mucosal barriers. Thus, this work aims at investigating the potential of utilizing nanostructured lipid carriers (NLCs) to overcome the aforementioned drawbacks and to enhance nose-to-brain drug delivery.MethodsBox-Behnken design was applied to explore the impact of solid lipid % (SL%, X1), liquid lipid % (LL%, X2), and sonication time (ST, X3) on particle size. The optimized NLC formulation was characterized and incorporated into gellan gum in situ gel. The prepared gel was subjected to in vitro drug release, in vivo pharmacokinetic performance, and histopathological assessment in rats.ResultsStatistical analysis revealed a significant negative effect for both SL% and ST on NLCs size. In contrast, a significant positive effect was observed for the LL%. The optimized formulation showed spherical shape with vesicular size of 114.63 nm. The optimized FLB-NLC in situ gel exhibited adequate stability and enhanced in vitro release compared to raw FLB control gel. The plasma and brain concentrations of the drug after nasal administration in rats increased by more than 3–6-fold, respectively, compared to raw FLB in situ gel. In addition, the histopathological studies revealed the absence of any pathological signs.ConclusionThe aforementioned results highlight the safety of FLB-NLC in situ nasal gel and its potential to improve the drug bioavailability and brain delivery.

Effects of Alcohol Administered With Flibanserin in Healthy Premenopausal Women: A Randomized, Double-Blind, Single-Dose Crossover Study

IntroductionFlibanserin is approved in the United States and Canada for the treatment of hypoactive sexual desire disorder in premenopausal women. AimThe purpose of this trial was to evaluate the safety of concomitant administration of flibanserin with alcohol. MethodsIn this single-center, randomized, double-blind, single-dose, crossover study, participants were randomly assigned to 1 of 12 sequences to receive each of 7 treatments: flibanserin 100 mg or placebo with ethanol 0.2 g/kg, 0.4 g/kg, or 0.6 g/kg, or flibanserin 100 mg only. Treatments were administered using a worst-case approach that included morning dosing and consumption of alcohol within 10 minutes. Main Outcome MeasureThe primary end point was the proportion of participants who experienced dizziness, syncope, or hypotension. Safety end points included orthostatic vital signs. ResultsThe study included 96 premenopausal women (mean age 31 ± 8 years). The incidence of dizziness for ethanol + flibanserin was 39.8% for ethanol 0.6 g/kg, 34.1% for 0.4 g/kg, and 27.4% for 0.2 g/kg compared with 31.1% for flibanserin without ethanol. Based on the available vital signs data, there was no effect of ethanol concentration on orthostatic blood pressure, vertigo, or hypotension; no instances of syncope were observed. The overall incidence of adverse events (AEs) was similar when flibanserin was administered alone (96.7%) or with ethanol (90.5–97.6%). Clinical ImplicationsConsumption of the tested amounts of alcohol (0.2–0.6 g/kg) does not have an additive effect on the AE profile of flibanserin 100 mg in healthy premenopausal women. Strengths & LimitationsStrengths include the study population (premenopausal women, as indicated for flibanserin) and range of ethanol doses. Limitations include the morning dosing of study medication, which is inconsistent with the bedtime dosing recommended for flibanserin, and the method of handling missing vital sign measurements. ConclusionCo-administration of flibanserin 100 mg with varying doses of ethanol resulted in few AEs of special interest, with no notable alcohol dose response. However, a significantly greater percentage of participants administered flibanserin with 0.6 g/kg and 0.4 g/kg of alcohol were characterized as “Participants in Whom Standing Blood Pressure Was Not Obtained” compared with participants administered flibanserin alone.Simon JA, Clayton AH, Parish SJ, et al. Effects of Alcohol Administered With Flibanserin in Healthy Premenopausal Women: A Randomized, Double-Blind, Single-Dose Crossover Study. J Sex Med 2020;17:83–93.

Dose-Finding Study of Lorexys for Hypoactive Sexual Desire Disorder in Premenopausal Women

IntroductionPrior medication treatment for hypoactive sexual desire disorder (HSDD) in women has left about half the subjects without benefit. Lorexys (LOR), a proprietary combination of the stimulating/excitatory dopamine-norepinephrine reuptake inhibitor bupropion (BUP) and the sedating/inhibitory serotonergic agonist-antagonist trazodone (TRZ), was developed as a multifunctional solution for this problem. AimTest efficacy, safety, and tolerability of LOR in a range of doses in a combined phase IB/IIA study in premenopausal outpatients with HSDD. MethodsOtherwise healthy premenopausal women from 25–50 years of age with HSDD were tested in an open-label, active-control, one-way crossover study, with three 4-week treatments of extended-release TRZ and/or sustained-release BUP. Evaluations were made before and after each treatment. A washout of at least a week followed each treatment. The order of treatments was a standard dose of BUP; a subtherapeutic dose of BUP and TRZ (LOR-low); and a threshold-therapeutic dose of BUP and TRZ (LOR-mod). A midpoint interim analysis was planned to consider adapting doses for efficacy or safety. Main Outcome MeasureThe primary efficacy measure was the Female Sexual Function Index, Desire domain; the main secondary efficacy measures included the Female Sexual Distress Scale-Revised 13th item, on bother about low desire, and a Patient’s Global Impression of Change. The main outcome comparison was the proportions of responders. Safety measures were elicited adverse events, Epworth Sleepiness Scale, Columbia Suicide Severity Rating Scale 6-item SCREEN version, vital signs, electrocardiograms, and standard laboratory tests. ResultsInterim analysis did not require altering doses. Most evaluable subjects responded to LOR-mod (at the standard thresholds for response based on minimum clinically relevant difference from baseline, 79% on Female Sexual Function Index, Desire domain, 87% on Female Sexual Distress Scale-Revised Item 13, and 79% on Patient’s Global Impression of Change; each P < .05 vs BUP). As expected, close to half responded to BUP (38%, 45%, and 52%, respectively). Response to LOR-low was intermediate (not significant vs BUP). Sensitivity analyses to compensate for carryover effects supported the efficacy of LOR-mod. Elicited adverse events showed the expected profile of TRZ, but led to no sedative-type dropouts or worsening on the Epworth Sleepiness Scale. Clinical ImplicationsThe open-label 1-way crossover design of this phase IB/IIA study limits conclusions, but the consistency of responder analyses showing superiority of LOR-mod dose over control, and the lack of central depressant dropouts, favor further development in double-blind placebo-control trials. Strength & LimitationsStrengths include large margins of efficacy over control agent, rapid onset of action, and rigorous safety assessment. Limitations are open-label, cross-over design/lack of placebo control and 1-month duration of exposure. ConclusionModerate-dose LOR was generally well-tolerated and was significantly more effective than BUP (active control). The results seem highly favorable compared to previously tested agents.Pyke RE, Clayton AH. Dose-Finding Study of Lorexys for Hypoactive Sexual Desire Disorder in Premenopausal Women. J Sex Med 2019;16:1885–1894.

Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder.

To evaluate the long-term safety and efficacy of bremelanotide as treatment for hypoactive sexual desire disorder in premenopausal women. Women who completed the 24-week double-blind core phase of RECONNECT, composed of two parallel phase 3 trials (301 and 302) examining the safety and efficacy of bremelanotide compared with placebo in premenopausal women with hypoactive sexual desire disorder, could enroll in the 52-week open-label extension, provided they had not experienced serious adverse events during the core phase. Efficacy was assessed using the coprimary endpoints from the core phase, and all adverse events were collected during the open-label extension. All statistical analyses were descriptive. The study 301 open-label extension began on July 17, 2015, and concluded on July 13, 2017; the study 302 open-label extension began on October 5, 2015, and concluded on June 29, 2017. Of the 856 eligible patients who completed the core phase, 684 elected to participate in the open-label extension, and 272 completed it. The most common treatment-emergent adverse events considered related to study drug were nausea (40.4%), flushing (20.6%), and headache (12.0%), and the only severe treatment-emergent adverse event experienced by more than one participant in both studies was nausea during the open-label extension. The change in Female Sexual Function Index-desire domain score and Female Sexual Distress Scale-Desire/Arousal/Orgasm item 13 from baseline to end of the open-label extension ranged from 1.25 to 1.30 and -1.4 to -1.7, respectively, for patients who received bremelanotide during the core phase, and 0.70-0.77 and -0.9, respectively, for patients who received placebo during the core phase. During the 52-week open-label extension of RECONNECT, no new safety signals were observed, and premenopausal women treated with bremelanotide exhibited sustained improvements in hypoactive sexual desire disorder symptoms. ClinicalTrials.gov, NCT02333071 (study 301) and NCT02338960 (study 302). Palatin Technologies, Inc., and AMAG Pharmaceuticals, Inc.

New Drug for Hypoactive Sexual Desire Disorder in Premenopausal Women.

Bremelanotide (Vyleesi) is now approved for the treatment of generalized hypoactive sexual desire disorder in premenopausal women.The drug may transiently increase blood pressure, induce focal hyperpigmentation, and produce nausea.Nurses and NPs should confirm that a patient's blood pressure is under control prior to starting bremelanotide.

Effects of Timing of Flibanserin Administration Relative to Alcohol Intake in Healthy Premenopausal Women: A Randomized, Double-Blind, Crossover Study

IntroductionFlibanserin is approved in the United States and Canada for the treatment of acquired, generalized, hypoactive sexual desire disorder in premenopausal women. Sedation-related side effects are among the most prevalent adverse events. Although infrequent, hypotension and syncope remain safety concerns because of possible interaction of flibanserin with alcohol. AimTo evaluate the impact of the timing of alcohol consumption on flibanserin safety and tolerability. MethodsIn this single-center, randomized, double-blind, placebo-controlled, 4-treatment crossover study, 64 healthy premenopausal women (mean age 32.5 ± 8.7 years; range 20‒52 years) received once-daily flibanserin 100 mg or placebo during each of two 10-day treatment periods. Study medication was administered on days 1–3 to achieve steady state. On days 4, 6, 8, and 10, after a standard breakfast, participants consumed 0.4 g/kg ethanol (approximately equivalent to two 5-oz glasses of wine) administered with orange juice 2, 4, or 6 hours before taking study medication or orange juice alone (no ethanol) 2 hours before taking study medication. OutcomesThe primary endpoint was percentage of participants experiencing syncope or orthostatic hypotension–associated adverse events requiring medical intervention. Secondary endpoints included the incidence of hypotension, the incidence of orthostatic hypotension, and rates of adverse events of special interest (syncope, orthostatic hypotension, dizziness, and somnolence). Results1 participant experienced a primary endpoint event (syncope) during treatment with placebo taken 4 hours after ethanol consumption. Within each ethanol dose–timing treatment, there were no statistically significant differences for flibanserin compared with placebo. Rates of hypotension were 53.3–66.7% after flibanserin dosing and 57.4–63.3% after placebo dosing. Rates for orthostatic hypotension were 0.0–5.0% after flibanserin dosing and 1.7–6.6% after placebo dosing. Clinical ImplicationsEthanol interaction with flibanserin was not observed in this study. Strengths & LimitationsThis study provides information regarding the use of flibanserin after the consumption of moderate amounts of ethanol (0.4 g/kg). However, daytime administration of flibanserin is not consistent with the drug’s indicated bedtime dosing. ConclusionFlibanserin, at steady state taken 2, 4, or 6 hours after 0.4 g/kg of ethanol intake did not increase the incidence of hypotension, orthostatic hypotension, or syncope compared with either flibanserin alone or ethanol alone.Simon JA, Clayton AH, Kingsberg SA, et al. Effects of Timing of Flibanserin Administration Relative to Alcohol Intake in Healthy Premenopausal Women: A Randomized, Double-Blind, Crossover Study. J Sex Med 2019;16:1779–1786.

Four solid forms of flibanserin: Insight into the crystal structures, properties, stability, and solid-state transition

Flibaserin is a drug for the treatment of hypoactive sexual desire disorder in pre-menopausal women. Four solid forms of flibanserin were discovered, including form A, form I, form II, and form III. The properties of these forms were characterized by powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis and Fourier transform infrared spectroscopy. Single-crystal structures of form A and form I were identified by single-crystal X-ray diffraction. The host molecule conformations, H-bonding interactions, as well as packing arrangements of these single crystals were analyzed. Besides, stability and solid-state transition of these forms were investigated.

FDA approves new treatment for hypoactive sexual desire disorder in premenopausal women

FDA approves new treatment for hypoactive sexual desire disorder in premenopausal women

025 Direct Determination of Kinetic and Equilibrium Binding of Flibanserin to 5HT1A and 5HT2A Receptors

Flibanserin is a 5HT1A receptor agonist and 5HT2A receptor antagonist that has been approved in the US and Canada for the treatment of acquired, generalized hypoactive sexual desire disorder in premenopausal women. The most frequently experienced adverse events associated with flibanserin use include sedation-related symptoms. Activation of 5-HT1A receptors has been shown to generally promote wakefulness and inhibit sleep while inhibition of 5-HT2A receptors has been shown to reduce wakefulness. Previous receptor binding studies have indirectly estimated flibanserin’s equilibrium affinity constants to different receptors by using a second, more readily available radiolabeled ligand. Furthermore, dissociation rates of flibanserin from 5HT1A and 5HT2A receptors have not been described in the literature. The objective of this study was to directly characterize equilibrium binding and kinetic dissociation parameters of flibanserin for 5HT1A and 5HT2A receptors. Flibanserin binding was determined in membrane preparations of cell lines overexpressing human 5HT1A receptors or human 5HT2A receptors. Membranes were incubated with 100 nM flibanserin for 3 h at 37°C and dissociation was induced by 10-fold dilution and immediate addition of 400-fold molar excess of WAY100635 (5HT1A subtype-selective receptor antagonist) or eplivanserin (5HT2A subtype-selective receptor antagonist) and aliquots were removed at varying time points for measurement. For saturation binding studies, cell membranes were incubated with increasing concentrations of flibanserin in the absence or presence of at least 200-fold molar excess of either WAY100635 or eplivanserin for 3 h at 37°C to determine total and non-specific binding. Membranes were collected with vacuum onto polyethylenimine-treated glass fiber filters, washed and extracted. Flibanserin was quantified by liquid chromatography and tandem mass spectrometry using positive ion mode electrospray ionization.

Evaluation of Flibanserin Safety: Comparison with Other Serotonergic Medications.

Flibanserin, a multifunctional serotonin agonist and antagonist, is approved by the U.S. Food and Drug Administration (FDA) for treatment of acquired, generalized hypoactive sexual desire disorder in premenopausal women. During the FDA's review of flibanserin, concerns were raised about the risks of hypotension, syncope, and sedation-related adverse events, which increase with alcohol use. Based on the results of an alcohol challenge study, the FDA required a boxed warning and alcohol contraindication in the flibanserin prescribing information, as part of a risk evaluation and mitigation strategy program. To evaluate the adverse event profile of flibanserin in the context of that seen with other medications that affect serotonin in the brain and are commonly prescribed for women. This was a review of data provided in the product prescribing information for flibanserin, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, other serotonergic antidepressants, and triptans. The incidence of adverse events was assessed. The incidences of hypotension, syncope, and sedation-related adverse events (eg, dizziness, somnolence, fatigue) in studies of flibanserin were within the ranges observed for serotonergic antidepressants; the rates of these adverse events were generally lower with triptan medications. Other flibanserin-associated adverse events (eg, nausea, insomnia, dry mouth) occurred more commonly in patients taking antidepressant medications. Although medications that affect the serotonin system have varying adverse event profiles (likely mediated by differences in serotonin-related mechanisms of action, specific brain structures affected, and effects on other neurotransmitter systems), the occurrence of central nervous system-related adverse events was not dissimilar between flibanserin and serotonergic antidepressants. Kingsberg SA, McElroy SL, Clayton AH. Evaluation of Flibanserin Safety: Comparison with Other Serotonergic Medications. Sex Med Rev 2019;7:380-392.

Sex, drugs, and rhetoric: The case of flibanserin for 'female sexual dysfunction'.

In August, 2015, the US Food and Drug Administration approved Addyi (flibanserin) for the treatment of Hypoactive Sexual Desire Disorder in premenopausal women. Ten months before that, the FDA had held a Patient-Focused Drug Development Public Meeting to address the 'unmet need' for a pharmaceutical to treat that condition. I attended that meeting as a rhetorical observer. This essay is an account of persuasive strategies used on, and then by, the FDA, as it considered approving a drug that was not convincingly either safe or effective. The essay turns on three texts: the 'Even the Score' pro-drug campaign that informed the patient-focused meeting, the text of the meeting itself, and the FDA's own published report of the event. I describe how a pharmaceutical company (Sprout, then owners of flibanserin) recruited, and then ventriloquized, both health professionals and members of the public to pressure the FDA to approve a sex drug for women - claiming that not to do so was evidence of sexism. I argue, with rhetorical evidence, that the case for approving flibanserin had already been won before Sprout submitted its application.

Flibanserin for hypoactive sexual desire disorder in premenopausal women.

Flibanserin is a mixed 5-HT1A agonist and 5-HT2A antagonist for treatment of premenopausal women with hypoactive sexual desire disorder. It is the first FDA-approved treatment for this disorder and can improve the number of satisfying sexual events. The drug has been associated with hypotension and syncope.

027 Effect of Alcohol Consumption on the Safety and Tolerability of Flibanserin in Premenopausal Female Volunteers

Addyi (flibanserin 100mg), is an orally administered, centrally-acting treatment for hypoactive sexual desire disorder in premenopausal women. Alcohol use is contraindicated due to Phase I study data suggesting increased risk of hypotension and syncope. Because the design of that alcohol challenge study [i.e., morning dosing of Addyi with high doses of ethanol (0.4–0.8 g/kg) consumed within 10 min] is inconsistent with prescribed dosing (q.h.s) and quantity of alcohol consumed in the general population, we assessed the effects of low-moderate alcohol use in premenopausal women taking Addyi as prescribed. Premenopausal women providing informed consent (n=24; mean age=38±6 y; mean BMI=24±3 kg/m2) consumed 1-2 glasses (125-250ml) of sulfite-free wine (12.5% ethanol) with a standardized 3-course dinner in a clinical research unit. Addyi was administered with 240 ml of water 5 min before bedtime (2.5 h after dinner). Subjects were awakened 8 h after dosing. Vital signs were assessed before and after dinner, and upon waking the next morning. Primary endpoints were the incidence and severity of adverse events (AEs) and changes in vital signs. Secondary endpoints were self-reported feeling of well-being and self-reported quality of sleep.

PND6 - Unmet Needs in the Management of Hypoactive Sexual Desire Disorder in Premenopausal Women

To gain insight into the diagnosis and management of hypoactive sexual desire disorder (HSDD) among premenopausal women reporting a diagnosis or symptoms of HSDD. A 30-minute, IRB-approved survey was designed to explore the patient experience and physical, social, mental, emotional, and economic burden related to HSDD. Inclusion criteria were ≥18 years of age, a diagnosis or symptoms of HSDD in accordance with the Decreased Sexual Desire Screener, currently in a stable, monogamous relationship with a partner for ≥6 months. Women with a bilateral oophorectomy or hysterectomy were excluded. 314 premenopausal women were included in the analysis. HSDD was most commonly managed by OB/GYNs (47.8%) or PCPs (35.5%). Among respondents who discussed their HSDD symptoms with their physician/therapist (n=203), 82.3% initiated the conversation themselves. While respondents generally had a positive perception of their physicians/therapists, 24.4% of respondents believed their HCPs were not aware of HSDD as a medical condition, and 16.7% of respondents felt their HCP did not take their concerns seriously. The most commonly prescribed treatments, lubricants (51.6%) and meditation/yoga (36.6%), were nonpharmacologic, which have no documented efficacy. Antidepressants or anti-anxiety medications were prescribed to 14.6% of respondents. Respondents who received nonpharmacologic treatments (n=243) generally found treatments safe but 35.8% cited poor efficacy; common reasons for ineffectiveness included no change in interest in sexual activity (65.8%) and inability to “stay in the moment” during sexual activity (57.6%). Although HSDD is recognized as a medical condition by ISSWSH (consensus review) and the APA (DSM-IV-TR), diagnosis and treatment are largely patient-initiated rather than HCP-driven. There is a need for improved HCP education, as many lack knowledge of how to diagnose and treat HSDD. Prescription patterns, which tend toward nonpharmacologic treatments, also suggest a lack of understanding of disease etiology and/or a paucity of approved and efficacious treatment options.

015 Efficacy of Flibanserin by Duration of Hypoactive Sexual Desire Disorder in Premenopausal Women

Flibanserin, a 5-HT1A agonist and 5-HT2A antagonist, is indicated for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. This post hoc analysis evaluated the efficacy of flibanserin treatment by duration of HSDD. Data were pooled from three 24-week, double-blind, placebo-controlled studies of flibanserin in premenopausal women with HSDD. Patients were stratified by HSDD duration (>6 months to 2 years, >2-5 years, and >5 years). Key measures of efficacy were the Female Sexual Function Index desire domain (FSFI-d) score, the Female Sexual Distress Scale-Revised item 13 (distress due to low desire; FSDS-R-13) score, and the number of satisfying sexual events (SSE). This analysis included 2344 premenopausal women (HSDD duration >6 months to 2 years, n=705; duration >2-5 years, n=830; duration >5 years, n=809) who received flibanserin 100 mg qhs or placebo. Improvement from baseline to week 24 in FSFI-d score (least-squares [LS] mean change) was significantly greater for flibanserin compared with placebo in women with HSDD for >6 months to 2 years (1.0 vs 0.8; P=0.010), >2-5 years (0.9 vs 0.6; P=0.004), and >5 years (0.9 vs 0.5; P<0.0001). Similarly, significantly greater improvement on the FSDS-R-13 (LS mean change) for flibanserin versus placebo was observed in women with HSDD duration of >6 months to 2 years (-1.0 vs -0.7; P=0.017), >2-5 years (-0.8 vs -0.6; P=0.027), and >5 years (-0.8 vs -0.5; P<0.0001) For SSE, improvement (LS mean change) with flibanserin relative to placebo was significantly different for HSDD duration >6 months to 2 years (2.7 vs 1.6; P=0.018) and duration >5 years (1.9 vs 1.2, P=0.003), but did not reach statistical significance, though trended, for duration of >2-5 years (1.9 vs 1.3; P=0.053). The most common adverse events associated with flibanserin (>5% of flibanserin-treated patients, overall) were somnolence (12.8% for flibanserin vs 3.4% for placebo) and dizziness (10.6% vs 1.5%).