Ospemifene vs. Conjugated Estrogens in the Treatment of Postmenopausal Sexual Dysfunction

Female sexual dysfunction (FSD) affects 57% of postmenopausal women. Vulvovaginal atrophy (VVA) is a condition that impacts up to 60% of the growing postmenopausal female population, and the most common symptom is dyspareunia. Women with FSD are 3.84 times as likely to also have VVA. Vaginal estrogen is the most common treatment for VVA, but it only marginally improves overall sexual function, and many women and clinicians avoid using it because of the risks of exogenous estrogen use during menopause. Ospemifene is a non-estrogen selective estrogen receptor modulator (SERM) that is FDA-approved for treating dyspareunia related to VVA, and has shown superb improvements in overall sexual health. This oral medication, taken daily, improves vaginal health, and has demonstrated protective activity in the breast and bone tissues. It also has not demonstrated any carcinogenic activity in the endometrium or liver. This study hopes to determine if ospemifene is superior to conjugated estrogens in improving sexual function and vaginal atrophy symptoms.

104 women will be randomized to receive 12 weeks of 60mg oral ospemifene, taken daily, or 12 weeks of 0.5mg vaginal conjugated estrogens, which is placed vaginally twice per week. Each participant will be informed of her assigned medication, and will receive a medication coupon to help offset the cost of the medication. Each medication is FDA-approved for long-term use of at least 52 weeks. For this study, a 12-week prescription for the medication will be sent electronically to the pharmacy of the participant's choice. The improvements in sexual health and VVA symptom severity will be compared in each group.

• Ospemifene (Drug), also known as Osphena: Ospemifene is a selective estrogen receptor modulator (SERM), and it is the only SERM approved in the United States to treat moderate to severe dyspareunia associated with VVA. It is an oral medication that is taken as a 60mg tablet once daily. Food intake increases its absorption by 2 to 3-fold, and this is not impacted by the fat or calorie content of the food. It is metabolized primarily in the liver, and is excreted in feces.
• Vaginal conjugated estrogens (Drug), also known as Premarin Vaginal Cream: Conjugated estrogens are a mixture of several different estrogen salts derived from natural sources and blended to approximate the composition of estrogens in the urine of pregnant horses. The main components are sodium estrone sulphate and sodium equilin sulfate. Vaginal estrogen is considered the medication of choice for treating vulvovaginal atrophy (VVA).

Primary outcomes

• Female Sexual Function Index Score [Baseline, Week 12]: The Female Sexual Function Index (FSFI) is a 19 item questionnaire that asks about sexual function in the prior four weeks. The FSFI was developed for the specific purpose of assessing sexual arousal, orgasm, satisfaction, pain related to sexual functioning in clinical trial participants. Participants answer by selecting between 5-6 question-specific options to rate the degree to which the question fits their experience. Each response option is assigned a point and each question has 0-5 or 1-5 possible points. The points are summed to determine a total score. The total score can range from 2 to 36 and scores equal to or less than 26.55 indicate female sexual dysfunction (FSD).
• Pain With Sex [Baseline, Week 12]: Participants reported pain with sex at the Baseline Visit and after 12 weeks of treatment. Participants rated the severity of their symptoms from 0 to 3, where 0 = none, 1 = mild, 2 = moderate and 3 = severe.
• Vaginal Dryness [Baseline, Week 12]: Participants reported vaginal dryness at the Baseline Visit and after 12 weeks of treatment. Participants rated the severity of their symptoms from 0 to 3, where 0 = none, 1 = mild, 2 = moderate and 3 = severe.
• Vaginal Itching [Baseline, Week 12]: Participants reported vaginal itching at the Baseline Visit and after 12 weeks of treatment. Participants rated the severity of their symptoms from 0 to 3, where 0 = none, 1 = mild, 2 = moderate and 3 = severe.
• Vaginal Irritation [Baseline, Week 12]: Participants reported vaginal irritation at the Baseline Visit and after 12 weeks of treatment. Participants rated the severity of their symptoms from 0 to 3, where 0 = none, 1 = mild, 2 = moderate and 3 = severe.

Sex: Female, ages: 40 Years to any

Inclusion Criteria:

* Interested in resuming or continuing sexual activity
* Greater than 12 months since last menstrual cycle or prior bilateral oophorectomy
* Dyspareunia as a vulvovaginal atrophy symptom
* Normal mammogram within 12 months prior to entry into the study

Exclusion Criteria:

* History or suspicion of breast carcinoma
* History of hormone-dependent tumor
* Genital bleeding of unknown cause
* Ongoing vaginal infection
* History of cerebrovascular accident (CVA), myocardial infarction (MI) or heart disease
* Uncontrolled hypertension (HTN) over 160/100
* Serious disease or chronic condition that may prevent completion of study
* Body Mass Index (BMI) over 40
* Hypercoagulable state, or currently on anticoagulant therapy
* Use of any exogenous sex hormone within three months from study entry, or during the study
* Pelvic surgery within the last 12 months

Participant flow

Outcome results

• Female Sexual Function Index Score (Primary), Number, units on a scale: Estrogen 9
• Pain With Sex (Primary), Number, units on a scale: Estrogen 2
• Vaginal Dryness (Primary), Number, units on a scale: Estrogen 3
• Vaginal Itching (Primary), Number, units on a scale: Estrogen 3
• Vaginal Irritation (Primary), Number, units on a scale: Estrogen 3

Adverse events

Time frame: Adverse event data were collected from the time the participant consented to take part in the study through the Week 12 Visit.

Limitations and caveats: The patient population did not provide as many interested and qualified subjects as anticipated, thus the study was terminated early due to obstacles with recruitment and time limitations for data analyses.

• Results publication: Lara LA, Cartagena-Ramos D, Figueiredo JB, Rosa-E-Silva ACJ, Ferriani RA, Martins WP, Fuentealba-Torres M. Hormone therapy for sexual function in perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2023 Aug 24;8(8):CD009672. doi: 10.1002/14651858.CD009672.pub3. PMID 37619252

• Study Protocol and Statistical Analysis Plan (PDF, 2017-11-27)

• Gina Northington, MD, PhD, Principal investigator, Emory University