The Efficacy and Safety of Ospemifene in Treating Dyspareunia Associated with Postmenopausal Vulvar and Vaginal Atrophy: A Systematic Review and Meta-Analysis
Yuanshan Cui MD; Huantao Zong MD; Huilei Yan MD; Nan Li MD; and Yong Zhang PhD
ONLINE: November 20, 2013 – The Journal of Sexual Medicine
DOI: 10.1111/jsm.12377
Introduction
Caused by the decrease in estrogen levels at menopause, vulvar and vaginal atrophy (VVA) is a condition that affects approximately 60% of postmenopausal women. Common symptoms include vaginal dryness, itching, burning, and dyspareunia. These symptoms typically persist and often do not improve without treatment.
Current treatments include systemic hormone therapy, vaginal estrogen products, and over-the-counter nonhormonal lubricants and moisturizers. These treatments are usually administered in low doses, as estrogen can have systemic side effects, especially over the long term.
Ospemifene is an oral selective estrogen receptor modulator (SERM). Past studies have shown that this drug is well tolerated.
The present study is a meta-analysis focusing on the safety and efficacy of ospemifene to treat dyspareunia associated with postmenopausal VVA.
Materials and Methods
Search Strategy
Using the MEDLINE, EMBASE, and Cochrane Controlled Trials Register databases, the research team searched for randomized controlled trials (RCTs) that focused on ospemifene in treating VVA. The reference lists of retrieved studies were also searched. Search terms included ospemifene, vulvovaginal atrophy, dyspareunia, and randomized control trial.
Inclusion Criteria and Trial Selection
Included RCTs met the following criteria:
• The study design included treatment with ospemifene.
• The study included accurate data that could be analyzed, including the total number of subjects and the values of each index.
• The full text of the study could be accessed.
Quality Assessment
Studies were classified into the following categories based on quality:
• A – All quality criteria were adequately met and the study had a low risk of bias.
• B – One of more of the quality criteria was only partially met or was unclear and there was a moderate risk of bias.
• C – One or more of the criteria was not met or not included and there was a high risk of bias.
Data Extraction
For each study, researchers made note of the first author and publication year, the study design and sample size, the therapy received by patients, and the country in which the study was conducted. The researchers also collected data on the changes in parabasal cells, superficial cells, vaginal PH, dyspareunia, and endometrial thickness.
Results
Characteristics of the Individual Studies
After eliminating articles that did not meet the inclusion criteria, six articles reporting on six RCTs were included. These studies compared ospemifene with a placebo. Together, the studies involved 1,772 patients. Three studies were short-term (12 weeks) and three were long-term (one year).
Quality of the Individual Studies
The quality of each study ranged from level A to level B. No evidence of bias was found.
Short-Term Ospemifene vs. Placebo
According to the researchers, the results of these studies suggested the following:
• Parabasal Cells. Ospemifene showed significant reductions in the parabasal cells compared to placebo.
• Superficial Cells. Ospemifene showed a statistically significant increase in the superficial cells compared to placebo.
• Vaginal PH. Ospemifene had significantly greater decreases in the vaginal PH.
• Dyspareunia. Ospemifene had significantly greater decreases in dyspareunia.
• Endometrial Thickness. Ospemifene showed greater rise in the endometrial thickness compared with placebo.
• Treatment Emergent Adverse Events (TEAE), Hot Flushes, Discontinuations due to Adverse Events (AE), and Serious Adverse Events (SAE). Ospemifene and placebo are similar in terms of the incidence of discontinuation due to AE and SAE.
Long-Term Ospemifene vs. Placebo
According to the researchers, the results of these studies suggested the following:
• Endometrial Thickness. Ospemifene showed greater increase in the endometrial thickness compared to placebo.
• TEAE, Hot Flushes, Discontinuations due to AE and SAE. Ospemifene and placebo are similar in terms of the incidence of hot flushes and discontinuation due to AE and SAE.
Discussion
The researchers noted that ospemifene 60 mg per day is “superior to placebo” in reducing parabasal cells, increasing superficial cells, decreasing vaginal PH, and reducing dyspareunia in short-term therapy. Compared to placebo, ospemifene improved the vaginal epithelium and vaginal PH, evidenced by reduced vaginal pain during sexual intercourse. The drug appeared to have consistent results over a 12-month treatment period.
Endometrial safety is an important concern. Women taking ospemifene did have increases in endometrial thickness, but the authors considered these increases to be “negligible.” In both short-term therapy and long-term therapy, no cases of endometrial hyperplasia or carcinoma were found in endometrial biopsies.
In short-term therapy, adverse reactions (such as TEAE and hot flushes) were higher among women taking ospemifene when compared to those taking the placebo. However, both ospemifene and placebo had similar discontinuation rates due to AE and SAE. Hot flushes were reported to be mild and did not increase discontinuation rates. Similar results were found in long-term therapy and ospemifene 60 mg per day was deemed to be “generally safe.”
The authors acknowledged that the number of studies involved in their analysis was small. They also noted that the short-term treatment duration was 12 weeks and that the studies of long-term treatment involved a small number of patients and did not include data on the efficacy of ospemifene in treating dyspareunia. Bias may have occurred because unpublished studies were not included in the analysis.
The authors called for more high-quality trials with larger samples.
Conclusion
They authors concluded, “This meta-analysis indicates ospemifene to be an effective and safe treatment for dyspareunia associated with postmenopausal VVA.
NOTE: In January 2014, the Journal of Sexual Medicine published an additional study about ospemifene. This research involved three double-blind, placebo-controlled clinical trials. In two trials, women were also given lubricants to try on an as-needed basis. The researchers found that ospemifene 60 mg/day was associated with an improvement in VVA. Lubricants are commonly used, but “effective pharmacological treatment options” may be needed for women with moderate to severe dyspareunia, as medication can address the underlying causes of VVA symptoms.
The authors concluded, “Ospemifene 60 mg/day is an effective and generally well-tolerated oral treatment alternative to estrogen therapy for moderate to severe dyspareunia in postmenopausal women with VVA.”