Comparison of the effect of licorice vaginal cream and estrogen vaginal cream on sexual function of postmenopausal women: An RCT

Abstract Background Menopause is a stage in woman's life that some women experience in middle age and some at a younger age (premature menopause). Low levels of ovarian hormones, during menopause can lead to various complications. Menopause is one of the factors that can affect a woman's sexual function. Objective The present study was conducted to compare the effect of licorice vaginal cream and estrogen vaginal cream on the sexual function of postmenopausal women. Materials and Methods In this randomized clinical trial study, 82 postmenopausal women who were referred to health centers in Ilam, Iran from July to November 2020 were randomly divided into 2 groups (n = 41/each). One group was given estrogen vaginal cream 2%, and the other vaginal licorice cream 2%. Participants used the 2 medications for 14-day periods each. We used the finite randomization method. Data collection questionnaires, including a demographic information questionnaire before treatment and a female sexual function index questionnaire were completed before, one month after the medication, and 2 months after using the medication. Results The mean score of sexual function in the licorice group was 17.86 ± 4.37 and increased to 20.31 ± 4.63 at the end of the study. The mean score of sexual function in the estrogen group was 17.14 ± 3.99 and increased to 22.97 ± 5.09 at the end of the study (p = 0.015). Conclusion The effect of estrogen vaginal cream on the sexual function of postmenopausal women was greater than licorice vaginal cream.


Introduction
Menopause is a stage in woman's life that some women experience in middle age and some at a younger age (premature menopause). This phenomenon is associated with various mental and physical changes and begins in the age range Sexual dysfunction is defined as a persistent or recurrent decrease in anorgasmia, dyspareunia and sexual arousal (6). Therefore, any disorder that leads to disharmony and as a result, dissatisfaction with sexual intercourse, can lead to sexual dysfunction. Menopause is one of the factors that can affect women's sexual function (7). In postmenopausal women, rugae are lost, and due to reduced vascularity, the appearance of the vagina is almost transparent and pale. Loss of elastic tissue and subcutaneous fat causes labia majora and labia minora to appear wrinkled. In addition, estrogen deficiency, which occurs after menopause, causes atrophic changes and can be associated with symptoms of genitourinary atrophy such as dyspareunia, itching, vaginal burning and vaginismus (involuntary tensing of the vagina) and dryness (6).
The therapeutic measures to improve sexual function during menopause fall into 2 categories; the first category is a hormonal replacement and the second category is the use of alternative and complementary therapies (8

Subjects
Sampling was done based on the following   In the present study, the instrument face and content validity and reliability were assessed again.

Ethical considerations
This article has been approved by the Ethics

Statistical analysis
Data were analyzed after they were entered into satistical package for the social sciences (SPSS),

Results
The present study was performed on 82 postmenopausal women referred to selected health centers in Ilam. Women who complained of sexual problems and dyspareunia were divided into 2 groups of 41 people ( Figure 1).
In the present study no significant difference was observed between the 2 groups in terms of duration of menopause, mean age, age at menarche and other mentioned demographic information (p > 0.05) ( Table I).
The results showed that the 2 groups were  (Table II).

International Journal of Reproductive BioMedicine
Ahmadizad et al.

Discussion
This study aimed to compare the effect of licorice vaginal cream and estrogen vaginal cream on sexual function of postmenopausal women.
Considering that the results showed no statistically significant difference between estrogen and licorice groups before the intervention, we can report that the 2 groups were homogeneous in terms of sexual function and individual characteristics.
The present study results showed that the use of licorice vaginal cream had a positive effect on increasing the symptoms of sexual desire, lubrication, satisfaction, orgasm, pain relief and arousal and sexual function increased significantly compared to before the intervention (p = 0.03). The use of estrogen vaginal cream also had a positive effect on increasing the symptoms of orgasm, sexual desire, satisfaction, pain, arousal, and lubrication. It was statistically significant compared to before the intervention (p = 0.02). Estrogen improves vaginal mucosa, increases elasticity, increases blood flow into the vulva and vagina, increases tissue thickness, and improves menopausal complications by increasing hyaluronic acid, polysaccharides, and maintaining the functional properties of vaginal epithelial cells (14). Estrogen affects the connective tissue of the reproductive system through 2 types of estrogen receptors, alpha and beta, and the phytoestrogens in plant extracts can bind to estrogen receptors. Since licorice contains phytoestrogenic compounds and the phytoestrogens in this plant act similar to female sex steroid hormones, the possible reason for this action of licorice cream seems to be the presence of estrogen-like compounds in it (14,15).
The present study demonstrated that the application of licorice vaginal cream can reduce vaginal dryness and subsequently increase vaginal discharge and lubrication, reduce pain, and increase sexual desire. In this regard, our result is consistent with similar study, which was conducted to investigate the effects of jazar supplement (herbal supplement containing Vitex, carrot and fennel seeds) on the QoL and sexual function and vaginal atrophy in postmenopausal women. The study was performed on 90 menopausal women. The participants were divided into 2 groups of 45 intervention and control, the intervention group consumed 4 jazar capsules (500 mg each) and the control group took a placebo for 8 wk. Data was collected using a demographic questionnaire, FSFI, and the Menopause-Specific QoL before the intervention and in week 4, 8, and 10. The results showed that the QoL and mean FSFI score increased significantly compared to the placebo group (p ≤ 0.001), and the study participants had a lower score for vaginal PH and were statistically significant (p ≤ 0.001) (16).
In the present study, vaginal licorice cream, similar to estrogen vaginal cream, significantly reduced dyspareunia in women with sexual dysfunction compared to before the intervention, which is consistent with the results of similar study in which soy isoflavone vaginal gel similar to estrogen vaginal cream improved dyspareunia in postmenopausal women (17).
The present study showed that by applying licorice vaginal cream and increasing sexual function, the QoL in postmenopausal women increases indirectly, which was not in conflict with the results of the study of Asgari and colleagues, to evaluate the effect of licorice on the QoL of postmenopausal women. Here, 380 mg of licorice extract 3 times a day or placebo were used in 2 groups of postmenopausal women. The results showed that the level of QoL was significantly increased in postmenopausal women. In their study, the QoL of 60 postmenopausal women in the 2 groups showed no statistically significant difference before the intervention, but one month after the intervention, a statistically significant difference was observed and shown in the total QoL, psycho-social, vasomotor and physical dimensions and it was shown that using licorice improves the QoL in postmenopausal women (11).
The present study, found that the mean vaginal lubrication in postmenopausal women who used licorice vaginal cream was 3.37 ± 1.08 before the intervention, which reached 4.009 ± 1.060 after the intervention. This difference was statistically significant (p ≤ 0.001). Furthermore, in this study, the mean dyspareunia in women using licorice vaginal cream was 3.75 ± 1.050 before the intervention, which reached 4.88 ± 0.91 after the intervention, which was statistically significant (p ≤ For the time being, non-hormonal options available for the treatment of sexual disorders caused by menopause include the use of dietary supplements and herbs containing phytoestrogens and isoflavones such as soy, licorice, red clover, fish oil, and gels and vaginal lubricants to improve and enhance the QoL in postmenopausal women (11). In the present study, licorice as a phytoestrogen indirectly increased the QoL due to increased sexual function, which was not consistent with the similar study, conducted to investigate the effect of red clover on QoL of postmenopausal women.
Fifty-five postmenopausal women participated in their study, of which 27 were in the placebo group and 28 were in the red clover group. At the end of the study, the results showed that the effect of the red clover supplement on the QoL of postmenopausal women was not different from the placebo (10).
In the present study, which was conducted to compare the effect of estrogen vaginal and vaginal licorice cream, the results showed that all 6 domains of the FSFI questionnaire improved after the intervention in the 2 groups of estrogen and licorice, and the difference was statistically significant. The comparison between the 2 groups showed that the increase in orgasm, sexual desire and satisfaction in the estrogen group was greater than in the licorice group. The difference was statistically significant (p = 0.01). The above results were in line with the results of other study, which was conducted to investigate the effect of fennel on the sexual performance of postmenopausal women. In the study, which was performed on 60 postmenopausal women. There were 30 people in the fennel group and 30 people in the placebo group, and each group received treatment for up to 8 wk. Sexual function was assessed using the FSFI, the results showed that in both groups 6 areas of FSFI improved while the difference was more visible in the fennel group (p ≤ 0.001) (19).
Sampling in more centers with higher population diversity, having 2 intervention groups, each of which acts as a control, no drop in samples at any stage of the study, follow-up and visit of patients up to 1 month after the last dose of the drug were the strengths of the study. The time limit of sampling in the field of sexual function studies was the most important limitation of this study due to cultural limitations.

Conclusion
The use of vaginal licorice cream reduces the symptoms of decreased sexual function (orgasm, sexual desire, lubrication, arousal, pain, sexual satisfaction) in postmenopausal women. In fact, it seems that the maximum effect that vaginal licorice cream has, helps to produce more estrogen in the body or at least maintain its level. The present study showed that the use of vaginal licorice cream over time can increase the score of sexual function symptoms in postmenopausal women and due to less systemic absorption of the drug can be a good option for women with sexual dysfunction. The present study, effect of estrogen vaginal cream on the sexual function of postmenopausal women was greater than licorice vaginal cream. Because the effect of many herbal supplements is determined by long-term use, it is recommended to use licorice for a longer period in the future.