Sexual Satisfaction and Function in Postmenopausal Women Treated with Herbal Medicines: A Review of Clinical Trials

Introduction

Menopause is a physiological period in women's life, whose most obvious symptom is defined as a permanent cessation of menstruation for one year resulting in a loss of ovarian follicles and estrogen reduction (1). Lower levels of ovarian hormones, especially estrogen, during menopause can lead to multiple physical, psychological, and sexual complications (2).

Vaginal atrophy is a frequently overlooked symptom of menopause, which is one of the factors affecting sexual satisfaction and function (3). Sexual satisfaction involves the feeling of the body, the need to touch, the interest in sexual activity, the communication needs of the individual with the sexual partner, and the ability to obtain satisfaction with sexual activity (4). Sexual dysfunction is defined as a persistent or recurrent decrease in sexual arousal, dyspareunia, and the presence of a problem or inability to achieve orgasm (5).

The results of studies (2018) on women in the United States indicate that sexual problems increase with age and disorders occurring within the age range of 18-44 (27.2%) and 45-64 years (44.6%) (6). In Iran, relative frequency of sexual dysfunction was reported to be in 72.4% of menopausal women, which is accompanied by abnormalities in the arousal phase (75.3%), disturbance in the phase of desire (62.6%), irregular orgasm (56.3%), dyspareunia (34.9%), and vaginismus (15.8%) (7). Different methods are used to prevent problems and improve sexual function during menopause, which are divided into two groups of complementary and alternative medicine and hormonal therapy (8). Estrogen therapy, either systemically or topically, causes increased
tissue thickness (9). Complications of alternative hormone therapy include gastrointestinal complications, weight gain, increased risk of breast and endometrial cancer, thromboembolism, and liver adenoma (10).

Medicinal plants have a close relationship with the history of human life; the use of medicinal herbs has always been a therapeutic approach (11). The results of a review study evaluating the effect of phytoestrogens on menopausal symptoms between 2013 and 2017 indicated a positive effect of phytoestrogens on the improvement of symptoms of menopause; however, a review of further articles over a wider time range is suggested to determine the effects of phytoestrogens on menopausal symptoms (12). Considering the numerous studies on the effect of medicinal herbs on sexual satisfaction and function of postmenopausal women, a current review was conducted to investigate the effect of medicinal herbs on sexual satisfaction and function of postmenopausal women.

Methods

Related English and Persian articles published between 2000 and December 2018 were searched through the databases of Iran Medex, PubMed, EMBASE, Scopus, and Science Direct. The articles were searched using the keyword of "menopause" through Boolean Operators of AND and OR with keywords of "sexual satisfaction", "sexual function", "herbal supplement", "diet supplement" and "Review Study in English and Persian" with all possible combinations and individually.

The inclusion criteria of the articles in this structured review were those which selected participants with no menstrual periods over the past 12 months and no use of medical drugs with estrogenic properties before the intervention. Moreover, the randomized human clinical trials published in Persian and English, which examined the effects of medicinal herbs on the sexual satisfaction and function of postmenopausal women were included in this study.

The articles were included in the study regardless of the method of use (oral, vaginal gel, aromatherapy), and which method of treatment was used for the control group. The initial review of the articles began from the abstracts so that the non-related items and duplicates were excluded from the review. The quality assessment and extraction of articles were performed according to the Jadad scale and by two independent individuals. An independent third person was assisted in case of any disagreement. This scale is directly related to bias control in clinical trials including generalized and randomized methods (score 0: no random allocation, score 2: full description of random allocation), blindness (score 0: no blindness, score 2: double- and triple-blind assessments) and dropout and withdrawal reports (score 1). Articles with a score of 3 or more have a good methodology (Table 1). Figure 1 summarizes the selection process of articles and the reasons for their exclusion from the study (13).

Table 2. Characteristics of studies included in the review study

Figure 1. Flowchart for selection of articles

Results

Of the 87 articles found, 20 articles with a sample size of 1555 people were included in this study. These selected articles consist of 3 articles on Ginkgo biloba, 3 articles on Bindii, 2 articles on Pueraria Mirifica, 2 articles on Ginseng, 2 articles on Fenugreek, 2 articles on Fennel, 2 articles on Aphrodit, 1 article on Liquorice, 1 article on date pollen, 1 article on red clover, and 1 article on aromatherapy. A summary of the included studies is shown in Table 1.

Fenugreek

The fenugreek, Trigonella foenum, belongs to family Fabaceae with steroidal compounds, such as saponin and diosgenin, which help maintain a balance of hormones (14). In a study conducted by Mazalzadeh et al. (2017), a significant difference was observed between Fenugreek and placebo groups regarding the severity of dyspareunia after the intervention (P<0.001). The mean sexual satisfaction scores in the treatment group were 44.28±3.52 and 74.18±1.94 before and after the intervention, respectively, indicating an increase after the intervention (P<0.001) (15). Shamshad Begum et al. (2016) conducted a study in which the intervention group consumed daily two 250-mg oral capsules of Fenugreek seed extract before breakfast and before dinner for a week. The drug dose was increased to 4 capsules if tolerated, and continued for 12 weeks. According to the obtained results, There was a significant difference between the two groups in terms of each sexual function variable, including the mean scores of sexual desires (P=0.03), orgasm (P<0.001), sexual satisfaction (P<0.001), and dyspareunia (P<0.04) (16).

Fennel

Fennel, Foeniculum vulgare, belongs to the family Apiaceae. This plant is rich in phytoestrogens, including lignans and isoflavones (17). In a study performed by Najar et al. (2015), there was an increase in the mean score of sexual satisfaction in the group using Fennel vaginal cream after the intervention (73.16±1.96), compared to the mean score of sexual satisfaction before the intervention (43.26±3.49, P<0.001) (18). In a similar study, Abedi et al. (2018) examined the effect of fennel vaginal cream on sexual function in postmenopausal women. The results revealed a significant difference between the two groups regarding the mean scores of sexual function dimensions, such as desire, arousal, orgasm, sexual satisfaction, and dyspareunia (P<0.001) (19).

Aphrodit

In a study carried out by Taavoni et al. (2014), the participants were randomly assigned to two groups of placebo and intervention who consumed Aphrodit capsules (40 mg of Bindii, 12.27 mg of ginger with active constituent of gingerol) (20) plus 3. 3 mg of saffron with active constituents of crocin and safranal (21) and 11 mg of cinnamon with active constituents of cinnamaldehyde and eugenol (22). On the other hand, the placebo group received capsules containing 60 g of starch for one month.

There was a significant difference between the two groups in terms of the mean score of sexual satisfaction (P=0.01) (23). In the same line, according to the results by Taavoni et al. (2016), the mean scores of orgasm before the intervention were 30.25±20.6 and 29±21.99 in the Aphrodit and the placebo groups, respectively. After one month of intervention, the mean scores of orgasm reached 41.12±10.08 and 29.12±29.6 in the Aphrodit and the placebo groups, respectively, indicating a statistically significant difference between the two groups (P=0.02). In addition, a significant difference was observed between the two groups after intervention in terms of the dimension of sexual desire (P=0.08) (24).

Liquorice

Liquorice, Glycyrrhiza glabra, belongs to the family Fabaceae, which has phytoestrogen properties. Some of the main compounds in this plant are triterpenoid saponin called glycyrrhizic acid or glycyrrhizin (25). Sadeghi et al. (2018) in a study aimed at determining the effect of Liquorice vaginal cream 2% on vaginal atrophy. According to the results, the categorical mean severity of dyspareunia in the Liquorice group was decreased from 2.74±0.61 on the first visit to 1.82±0.70 on the second visit. In addition. It was reduced from 0.60±0.73 to 0.23±0.05 on the third and fourth visits, respectively (26).

Ginseng

Ginseng contains a steroid glycoside called ginsenoside. The ginsenoside, also called triterpenoid saponin or sometimes panaxoside, can be found in the root of ginseng (27).

In a study performed by Oh KJ et al. (2010), there was an increase in the mean total score of sexual function in the ginseng capsule group from 21.10 to 22.95; however, this difference was not significant, compared to the placebo group (P=0.146). A significant difference was observed between the two groups in terms of the number and level of satisfaction with arousal (P<0.05) (27). The results of a study by Brooks et al. (2008) reported the mean score of sexual dysfunction 6 weeks after taking Maca to be 22.9% and 34.6% lower than the cases reported at the baseline and after placebo intake (P<0.05) (28).

Red clover

Red clover, Trifolium pratense is one of the species in the Trifolium genus. Genistein and Daidzein are the main isoflavonoids found in red clover (29). In a study by Chedraui et al. (2006), the intervention group received 90 days of treatment with oral red clover capsules. After a week without taking medicine, the position of intervention and control groups changed, so that the control group was treated for 90 days. The evaluation was performed on days 90 and 180 after the intervention. According to the results, dyspareunia decreased from 78.8% before the intervention to 34.6% after the intervention in the treatment group. Moreover, it was 69.2% in the placebo group after taking the Red Clover capsule. The rate of lower levels of sexual desire was 94.3% which was decreased to 52.8% and 73.6% in the intervention and placebo groups, respectively (30).

Pueraria Mirifica

Pueraria Mirifica belongs to the family Leguminosae and is a good source of phytoestrogens. Miroestrol and deoxymiroestrol present in this plant have molecular structures similar to those of estradiol (31). According to the results of a study performed by Suwanvesh et al. (2017), the dyspareunia in each group was reduced by 6% using P. Mirifica root vaginal gel and conjugated equine estrogen cream (P<0.05); however, there was no significant difference between the two groups in this regard (P>0.05) (32). In a study conducted by Manonai et al. (2007), the frequency of dyspareunia in the intervention group who consumed oral P. Mirificacapsule was decreased from 56.9% to 39.2%, while no change was seen in the placebo group (33).

Ginkgo biloba

Ginkgo biloba, commonly known as ginkgo, belongs to the Ginkgoaceae family and contains 24% flavonol glycosides (34). In a study carried out by Amiri et al. (2012), the intervention group was administered by a 220-240-mg capsule of Ginkgo (120 mg for the first week and 240 mg daily as tolerated treatment remaining for 3 weeks). The results showed no significant difference between the two groups of Ginkgo biloba and placebo regarding sexual satisfaction one month after the intervention (P=0.31) (34). Furthermore, Amiri et al. (2014) prescribed a capsule (60 mg) of Ginkgo biloba daily for the intervention group (after a week, if the digestive problems appeared, the same dose was continued, but if tolerated, the dosage was increased to 4 times a day). Based on the results, sexual desire was improved in the intervention group after a month (P<0.05) (35). In a study performed by Malakouti et al. (2017), there was a significant difference between the three groups in terms of the total score (P<0.001) and all dimensions of sexual function (P<0.003), except for dyspareunia and sexual satisfaction (36). In another study, Malakouti et al. (2016) examined the effects of combined inhalation aromatherapy on the sexual function of postmenopausal women. The results showed a significant difference between the aromatherapy and placebo groups regarding the total score (P<0.001) and all dimensions of sexual function (P<0.003), except for dyspareunia (37).

Bindii (Tribulus terrestris)

Bindii (Tribulus terrestris) is an annual herbaceous plant that triggers spermatogenesis and increases LH and testosterone levels due to the presence of estradiol (38). According to the results of a study conducted by Shojaei et al. (2016), the mean total score of sexual function was significantly higher in the intervention groups after the intervention (Bindii extract with concentrations of 0.5, 0.7, 0.9), compared to the mean total scores obtained before the intervention (P<0.05).

After two months, there was a significant increase in the mean score of sexual satisfaction in both groups consuming Bindii extract with concentrations of 0.7 and 0.9, compared to the mean scores obtained before the intervention (P<0.05) (39). In the same line, de Souza et al. (2016) examined the effects of Bindii extract and placebo on the individuals 120 days after treatment in terms of the sexual function variables, including sexual desire, arousal, orgasm, dyspareunia, and sexual satisfaction. The results revealed a significant difference between the two groups regarding the aforementioned variables (P<0.01) (40). Postigo et al. (2016) reported improvements in sexual function up to 20% and 70% in the placebo and the intervention groups treated with Bindii extract, respectively (P<0.001). Moreover, a statistically significant difference was observed before and after the treatment in the intervention group in terms of the sexual function variables, including sexual desire, arousal, dyspareunia, and sexual satisfaction (P<0.01); however, this difference was not significant in orgasm domain (P=0.28) (41).

Date

Date (Phoenix dactylifera) contains natural antioxidants, such as flavonoids, glycosides, saponins, and estrogens (42). In a study conducted by Yousefzadeh et al. (2017), the mean change in orgasm score in postmenopausal women after oral administration of date pollen was significantly higher than that of the control group (P=0.004); however, the mean change in sexual satisfaction scores after the intervention was not significant in both intervention and control groups (P=0.122) (43).

Discussion

The present study was conducted on 20 articles containing 10 different herbs and 2 combined herbal remedies with the aim of investigating the effect of medicinal herbs on sexual satisfaction and function of postmenopausal women. In the study conducted by Yousefzadeh et al. (2017), the use of date pollen capsules improved orgasm in postmenopausal women; however, it had no effects on sexual satisfaction. The researchers argued some of the reasons for sexual ineffectiveness as individual's attitudes toward life, the type of personal responsibility, the effect of environment on sexual relations, the quality of relationships, and inhibitors, such as anxiety, fear, and discomfort. They recommended that further studies be conducted with wider drug dosage and longer intervention periods (43).

Mazalzadeh et al. (2017) found it helpful to use fenugreek vaginal cream to increase the sexual satisfaction of postmenopausal women (15). In the same line, Shamshad Begum et al. (2016) showed that oral capsule containing fenugreek extract improved sexual function in postmenopausal women (16). The saponin and the diosgenin present in the Fenugreek extract are phytoestrogens capable of binding to estrogen receptors, which maintain the endothelial function of the vaginal mucous membranes (15).

Moreover, in a study conducted by Najar et al. (2015), the improvements in vaginal atrophy, dyspareunia, and sexual satisfaction were evident after 8 weeks of treatment with fennel vaginal cream, compared to the placebo group (18). Abedi (2018) reported the effect of Fennel vaginal cream on the improvement of sexual function during menopause. Possible cause of such an effect is the role of phytoestrogens, whose mechanism can be aligned with the effect of the intervention. The results of three clinical trials evaluating the effect of Bindii on the sexual function of postmenopausal women indicated that Bindii had significant effects on sexual function (19).

Sadeghi (2018) showed that the use of Liquorice vaginal cream has a positive effect on the reduction of mental symptoms, such as vaginal dryness, itching, irritation, and dyspareunia in postmenopausal women, compared to placebo (26). Furthermore, Taavoni et al. (2016) stated the remarkable effects of Aphrodit on sexual satisfaction (24). In another study (2014), they revealed that Aphrodit could improve orgasm and sexual desire in postmenopausal women (23). In a study performed by kyung-jin (2010), ginseng was found to have a positive effect on sexual satisfaction; however, it was accompanied by vaginal bleeding (27).

Nevertheless, ginseng (Maca) reduced sexual dysfunction based on the results of a study performed by Brooks (2008) (28). In the study conducted by Amiri (2014), despite the effectiveness of Ginkgo biloba herbal supplement on women's sexual desire, the results showed no effect on the frequency of sexual activity. Considering that the effectiveness of many herbal supplements will appear after long use, this plant was recommended to be used for a longer period in subsequent studies (34).

In two other studies aimed at determining the effect of Ginkgo biloba capsule on sexual satisfaction in postmenopausal women, the results revealed that Ginkgo biloba led to no improvements in sexual satisfaction. Headache was one of the side effects of taking the pill. Given that several factors can affect the sexual relations of postmenopausal women, the ineffectiveness of Ginkgo biloba on sexual satisfaction can be based on its inability to affect factors, such as sexual knowledge and psychological factors (35-36).

The results of combined aromatherapy examination on sexual function indicated that this method was effective; however, it had no effect on dyspareunia and sexual satisfaction (37-36). Chedraui et al. (2006) concluded that oral red clover capsules reduced dyspareunia and vaginal dryness leading to the improvement of sexual desire (30). The effect of P. Mirifica on atrophy and dyspareunia in postmenopausal women was investigated in two studies. According to the results, P. Mirifica had an estrogenic effect on vaginal tissue and improved dyspareunia, vaginal dryness, and atrophy symptoms. Mastalgia, dizziness, and nausea were reported as complications of oral P. Mirifica (31-32).

Implications for Practice

Plants of Bindii, Fenugreek, Fennel, Liquorice, P. Mirifica, Ginseng, Red clover, and Aphrodit had positive effects on dyspareunia, sexual satisfaction, and sexual function. On the other hand, date pollen and Ginkgo biloba capsule had no effects on sexual satisfaction; moreover, Ginkgo biloba pills were ineffective in the improvements of dyspareunia and sexual satisfaction. A large variety of plants and the type and level of phytoestrogens in the study products prevented meta-analysis. The weak methodology of some studies, the lack of reporting on the exact characteristics of the drug or side effects, the use of different tools to measure variables and lack of access to the text of some articles emphasize the need for more detailed studies on the identification of the therapeutic effects of herbs on sexual satisfaction and function. In addition, it is recommended to conduct comparative studies with similar doses and compare the effects of these plants.

Acknowledgments

This study was extracted from a research project approved by Mashhad University of Medical Sciences, Mashhad, Iran, with the registration number of 970386. We would like to appreciate the Research Deputy of Mashhad University of Medical Sciences for their financial support.

Conflicts of Interest

The authors declare that there is no conflict of interest regarding the publication of this paper.