Menopause is the end of monthly cycles caused by a decrease in the release of the ovarian hormones progesterone and estrogen [1]. Natural menopause, which occurs in most women between the ages of 49 and 52 years, is identified after a year of amenorrhea and is not associated with any medical conditions [2]. A group of signs and symptoms is associated with the recently coined term “genitourinary syndrome of menopause” (GSM). Vaginal dryness and dyspareunia, or discomfort during sexual activity, are the primary symptoms associated with GSM. Between 27% and 60% of women experience menopause with vaginal dryness or dyspareunia. The absence of estrogen production causes the skin and supporting tissues of the vulva and vagina to become less elastic and thinner, and the vagina to become dry. These modifications may result in post-coital hemorrhage, burning, fissuring, and dyspareunia [3,4].

Treating the needs and symptoms of women individually is the best way to manage menopausal symptoms. Estrogen has been used as a hormonal therapy for many years to treat menopausal symptoms [5]. However, hormonal therapy is no longer recommended for individuals with breast or uterine cancer, cardiovascular disease, or history of thromboembolic events [5]. Despite limited of scientific evidence on their benefits and risks, interest in non-hormonal therapies among postmenopausal women has increased, as they consider these options as more natural or are concerned about the adverse effects of estrogen [6,7].

Plant-based compounds called phytoestrogens attach to estrogen receptors and exhibit mild anti-estrogenic and estrogenic properties. Isoflavone is a phytoestrogen commonly used in the management of menopausal symptoms [8]. Isoflavones are flavonoids derived from soy that have organ-specific estrogenic and antiestrogenic effects because they compete with estradiol for the same receptor sites and bind weakly to the estrogen α-receptor and more strongly to the E β-receptor [9,10].

Several interventional studies have examined the effectiveness of phytoestrogens in treating menopausal symptoms. Johnson et al. [11] reported a significant improvement in menopausal symptoms after consuming diets high in phytoestrogens. Similarly a study by Khapre et al. [12] stated that soy isoflavone supplementation benefits both perimenopausal and postmenopausal women. According to certain studies, most women reported that their vaginal dryness did not change or improve, with no major intergroup differences [13]. This study aimed to evaluate the effects of isoflavones on vaginal dryness and dyspareunia in postmenopausal women.

The Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (were adhered to in this systematic review.

An electronic search of three primary databases (PubMed, ScienceDirect, and Cochrane) yielded 375 potential articles. After removing the duplicates, 231 records were screened based on their titles and abstracts. Four independent reviewers selected 50 studies for full-text article assessments. After 40 studies were deemed ineligible, 10 were included in the analysis. The PRISMA flowchart was used to illustrate the procedure for this systematic review (Fig. 1). Table 1 lists the details of the included studies. Ten RCTs with 675 participants, published between 2000 and 2024, were included in our analysis [15-24]. For more than a year, studies have assessed postmenopausal women with amenorrhea.

Fig. 2 presents the results of the quality assessment. Four trials in D1 had a moderate risk of bias [20,21,23,24]. Only one study on D2 was considered to have a risk of bias [22]. The two studies on D3 [23,24] and D4 [18,20] raised doubts regarding the possibility of bias. All studies included in D5 described findings regarding the study’s goals and had a low risk of bias rating.

Hormonal therapy (HT) is an effective treatment for vaginal dryness and dyspareunia in postmenopausal women [25]. The decline in estrogen produced by the ovaries after menopause has been linked to increased health risks such as changes in connective tissue, metabolic disorders, genitourinary complaints, sleep disorders, and depressive disorders [26]. Therefore, estrogen supplementation may protect against these diseases. However, some studies have reported that hormonal therapy is associated with an increased risk of breast cancer, stroke, and other side effects [6,27]. Isoflavones bind to estrogen receptors and are classified as phytoestrogens. As phytoestrogens do not bind to estrogen receptors as firmly as endogenous estrogen, their weaker estrogenic effects can minimize undesirable side effects, making isoflavones a potential alternative to HT for relieving vaginal dryness and dyspareunia in postmenopausal women [28].

Our study found that although isoflavones could significantly relieve vaginal dryness, they did not significantly improve dyspareunia symptoms in postmenopausal women. This finding aligned with a randomized, double-blind, controlled clinical trial by Carmignani et al. [19], which showed a significant improvement in vaginal dryness in the isoflavones group according to the menopause rating scale. Similarly, Chaudhary et al. [29] found that >85% of women in the isoflavone group experienced relief from vaginal dryness after three months of treatment. Nikander et al. [13] also reported a statistically significant improvement in vaginal dryness, with a reduction in subjects affected by vaginal dryness by 85.7% (P<0.001). Other studies have also evaluated the effects of isoflavones on dyspareunia. Kotsopoulos et al. [21] conducted a double-blind, placebo-controlled trial and found that isoflavones did not alleviate dyspareunia in postmenopausal women and worsened it compared to the placebo group. However, some studies, such as those by Lima et al. [20] and Najaf Najafi and Ghazanfarpour [30], reported contradictory results. Lima et al. [20] conducted a double-blind randomized placebo-controlled study and found that isoflavone gel was beneficial for alleviating moderate and intense dyspareunia symptoms. Najaf Najafi and Ghazanfarpour [30] stated that soy significantly improves dyspareunia, although it does not affect sexual dysfunction.

The strengths of this study include addressing a significant and often under-researched issue in women’s health, and providing valuable insights into non-hormonal treatment options, especially isoflavones, for menopausal symptoms. This can guide clinicians in counseling postmenopausal women about the potential benefits and limitations of isoflavones in the management of vaginal dryness and dyspareunia. This may also inspire further investigations into the optimization of the use of isoflavones, including the most effective formulations or dosages. Our limitations in this study are as follows: first, only two and four studies, respectively, were included in the analysis for dyspareunia and vaginal dryness, involving a total of 61 and 95 participants, respectively, which may not represent the entire body of research on the effects of isoflavones on these conditions. Second, high heterogeneity was observed in the analysis, as indicated by I² values of 93% for vaginal dryness and 98% for dyspareunia. Investigating the sources of this heterogeneity through a subgroup analysis was impossible because of the limited number of studies included. Third, publication bias may have influenced the results as unfavorable studies were less likely to be published. In addition, our research strategy may have overlooked critical studies.

This systematic review and meta-analysis provides valuable insights into the potential role of isoflavones as alternatives to hormone therapy for alleviating vaginal dryness in postmenopausal women. Our findings suggest that isoflavones are a promising alternative to hormonal treatments with minimal side effects. However, their efficacy in addressing dyspareunia remains inconclusive owing to high heterogeneity and the limited number of studies. This study highlights the need for further research to solidify the scientific evidence on the benefits of isoflavones, particularly with larger sample sizes and lower study heterogeneity. In addition to our understanding of nonhormonal treatments for vaginal dryness and dyspareunia in postmenopausal women, this review provides key insights for future clinical trials and can aid in making treatment decisions.