Comparison of the Effects of Elaeagnus angustifolia Flower Capsule and Sildenafil Citrate Tablet on Anxiety Resulting From Sexual Dysfunction in Women Referring to the Selected Clinics of Shiraz University of Medical Sciences

Abstract

Dissatisfaction from sexual relationships can result in deprivation as well as problems, such as depression, anxiety, and destruction of family’s mental health. One hundred twenty-five women (18 to 40 years) who suffered from hypoactive sexual desire disorder were divided into Elaeagnus angustifolia flower (4.5 g g daily for 35 days), sildenafil citrate tablet (50 mg for 4 weeks), and control groups. The study data were collected using the Female Sexual Function Index and Spielberger’s questionnaire and measurement of thyroid-stimulating hormone and prolactin hormone. In the Elaeagnus angustifolia group, the mean score of state and trait anxiety decreased after the intervention. In the sildenafil citrate group also, the mean score of state anxiety decreased from 22.15 ± 4.98 to 20.1 ± 5.15 (P = .001) and that of trait anxiety decreased from 23.07 ± 4.44 to 21.55 ± 4.82 (P = .002) after the intervention. Consumption of sildenafil citrate tablet was effective in reduction of the mean score of anxiety resulting from sexual dysfunction.

Keywords

anxiety sexual desire disorder sildenafil citrate

Sexual function is an important and essential component of a women’s life.¹ Sexual function is highly complex and is affected by a large number of factors.² It is in fact the result of a complex interaction of physiological, social, and mental factors and is affected by anxiety, stress, communication problems, aging, menopause, comorbidities, and medications.³ Some researchers believe that sexual function is far beyond just sexual behavior, and in case this need is not satisfied, it will impose lots of physical and mental pressures on individuals and lead to anger, violence, depression, anxiety, drug abuse, inability for parenting and child care, inability to have a healthy emotional relationship, and disability to flourish one’s abilities and creativity in the society⁴ and also affect the quality of interpersonal relationships.⁵ An earlier study in the Netherlands indicated a correlation between mental distress and reduction of sexual desire.⁶

According to the revised definition of the Diagnostic and Statistical Manual of Mental Disorders by the American Psychiatric Association, sexual desire is the first of the 4 stages of sexual function response (desire, arousal, orgasm, and resolution) that does not present only with physiological features; rather, it is the reflection of individuals’ motivations, backgrounds, and mental dimensions.⁷

Basson also proposed a circular model for sexual cycle in which emotional intimacy and physical satisfaction are the main factors.⁸ This model involves various physiological, organic, and psychological factors that might have an impact on women’s sexual response.

In many cases, hidden and unexpressed sexual problems can present with physical problems, depression, marital conflicts, and anxiety and may also lead to severe familial problems and even divorce.⁹ The available statistics regarding divorce, which is one of the most reliable indicators of marital conflicts, prove that marital satisfaction cannot be easily achieved.¹⁰ Marital dissatisfaction can also result in weaker health status, depression, personality problems, inappropriate behaviors, and weak social status.¹¹ On the other hand, expression of love in sexual relations increases marital satisfaction and reduces psychological problems. Studies have indicated that 40% of women have experienced sexual dysfunction.¹² Another study demonstrated that one third and one fourth of the women suffered from lack of sexual desire and orgasmic disorder, respectively.¹³ One other study reported at least one type of sexual disorder in 37.9% of women.¹⁴ Furthermore, a study was conducted on 2467 women aged between 20 and 70 years from France, Germany, Italy, and England. Among the 20- to 49-year-old women, the prevalence of hypoactive sexual desire disorder was 6% in premenopausal women and 16% in those experiencing menopause due to surgery. In women aged between 50 and 70 years also, the prevalence rate of this disorder was 9% among the menopausal women and 12% among those experiencing menopause due to surgery.¹⁵ Another prior study showed the prevalence of sexual dysfunction in pregnant women to be 23.4%, 30.5%, and 46.2% in the 1(st), 2(nd), and 3(rd) trimesters, respectively.¹ In a research study in Tehran also, the mean of female sexual dysfunction was 20.9%.^16
–18

Although female sexual dysfunction is affected by complex physiological and mental factors, herbal and chemical medications can to some extent improve this important issue, sexual health, and anxiety, which are the most common mental problems among women. Anxiety is defined as a psychobehavioral outcome resulting from being faced with stressful situations.¹⁹

Despite the importance of female sexual dysfunction, limited treatment methods are available in this regard including psychotherapy (training and marital consultation),^20
–22 pharmacological treatment (hormone therapy),^23

–26 phosphodiesterase type 5 (PDE5) inhibitors,^27,28 and complementary medicine (herbal medicine).²⁹ In addition, the main mechanism of sildenafil citrate is increasing the effect of nitric oxide (NO) through inhibition of cyclic guanosine monophosphate (cGMP) degradation.³⁰ cGMP in both vagina and males’ sexual organs leads to inactivation of PDE5 inhibitors. It also exists in clitoris and labia smooth muscles. Consumption of sildenafil citrate, through the aforementioned mechanism, causes tissue hyperpolarization and relaxation, eventually leading to increase of blood flow, congestion, and inflation.³⁰ Sildenafil citrate is effective in female sexual function, particularly sexual arousal.¹⁹ Its effects on sexual arousal, lubrication,³¹ and relaxation of smooth muscles especially in vaginal arteries, veins, and capillaries, and clitoris have also been mentioned in other studies.³² Nevertheless, some researchers believe that the complete role of this mechanism in vaginal congestion as a response to sexual arousal is still unknown.³³

In general, various plants, including ginseng, yohimbine, rose flower extract, and E angustifolia flower, have been used in traditional medicine to treat sexual dysfunction. Since Elaeagnus angustifolia flower exists in Iranian traditional medicine and no studies have been conducted in this regard, the researchers of the present study decided to use this plant for treatment of sexual dysfunction. Elaeagnus angustifolia is among the medicinal plants that, according to the specialists of traditional medicine, is hot and dry, is aromatic, and can stimulate sexuality especially in young girls and women.³⁴

It is an Asian tree belonging to the family Elaeagnaceae and grows in a wide range of environmental conditions.³⁵ Elaeagnus angustifolia is native to northern Europe and Western Asia, including Iran, and has spread across the Himalayas. In English, it is called a measure of long oval leaves with pointed tips and short petioles.³⁶ The plant grows in Western Asia, including Iran. Iranians traditionally use its fruit as a painkiller for patients with rheumatoid arthritis, and its flowers are traditionally used for the treatment of tetanus. Fruits and flowers of the plant are also used to treat nausea, vomiting, jaundice, asthma, and abdominal distention.³⁷

A search has shown that this herb has antiulcerogenic, muscle relaxation, and inflammation effects, and it is also used in traditional medicine. Elaeagnus angustifolia is also used to treat symptoms of rheumatoid arthritis.³⁸ A study has shown that Elaeagnus angustifolia L fruit seeds have muscle relaxant effect on mice,³⁹ so the leaf and flower include phenolic and flavonoid components. These compounds have antioxidant properties that protect cells from the damage.³⁶ Bendaikha and colleagues reported that 7 acylated flavonol glycosides called elaeagnosides AG have been isolated from the flowers of Elaeagnus angustifolia. In addition to the 7 flavonoids, known measures of flowers have been previously reported.⁴⁰ Due to the widespread use of plants of Elaeagnus angustifolia in traditional medicine of Iran and with regard to the relaxation properties reported in several studies,^38,39 the present study aims to compare the effects of Elaeagnus angustifolia flower capsule and sildenafil citrate tablet on anxiety resulting from sexual dysfunction in women referring to the selected gynecology clinics of Shiraz University of Medical Sciences, Shiraz, Iran, and compare the results to the placebo group receiving no intervention. In case the effectiveness of this herbal supplement is approved, it can be provided for the couples as a method with lower complications, so that various problems resulting from anxiety associated with sexual dysfunction can be reduced.

Materials and Methods

This study was a randomized clinical trial. Based on the previous studies conducted on the issue,^3,41
–43 according to the study objectives and design, considering an error of 5%, power of 80%, least mean difference of 0.6, and variance of 0.92, and using the following formula, a sample size of 108 participants was determined for the study (36 in each group):

n = \frac{2 (z_{1 - (α / 2)} + z_{1 - β}) δ^{2}}{d^{2}} .

However, considering a loss rate of 10% and using the formula given below, the sample size was increased to 42 participants in each group:

n^{'} = n \times \frac{1}{1 - p} .

Overall, 140 eligible women were entered into the study, but only 125 completed the study (41 in the Elaeagnus angustifolia flower capsule group, 42 in the sildenafil citrate group, and 42 in the control group). The study participants included 18- to 40-year-old women suffering from sexual dysfunction who had referred to the selected clinics covered by Enqelab Health Center (Figure 1). The inclusion criteria of the study were obtaining scores <22 in Female Sexual Function Index (FSFI), not being pregnant, not breastfeeding, not having a history of cardiac arrest, hypertension, and vascular diseases (according to patients’ records), not using effective drugs in sexual function such as common antidepressants, not suffering from dyspareunia or vaginismus, not having a history of headaches such as migraine headaches, not consuming hormonal drugs particularly oral contraceptive pills, not using alcohol, and not smoking.

Figure 1.

Consort flow diagram.

The study data were collected using a demographic information form and FSFI and measurement of thyroid-stimulating hormone and prolactin hormone. Women’s sexual function was assessed using FSFI.⁴⁴ This index includes 19 items evaluating women’s sexual function in 6 independent areas, namely, desire, mental arousal, lubrication, orgasm, satisfaction, and pain during intercourse.^44,45 The women were required to answer the items based on their sexual feeling and function during the past 4 weeks. A score between 0 and 5 is assigned to the items of FSFI, with scores ≤28 representing sexual dysfunction. However, since pain (6 points) was omitted from the present study, a score of 22 was considered instead of 28 (Table 1).

Table 1.

The score of different domine of Female Sexual Function Index (FSFI).

Dimension	Questions	Range of Scores	Coefficient	Minimum	Maximum
Desire	1, 2	1-5	0.6	1.2	6
Arousal	3, 4, 5, 6	0-5	0.3	0	6
Lubrication	7, 8, 9, 10	0-5	0.3	0	6
Orgasm	11, 12, 13	0-5	0.4	0	6
Satisfaction	14, 15, 16	0(1)-5	0.4	0.8	6

The reliability and validity of this index were approved by Mohammadi et al in 2008. Accordingly, the reliability of the scale and its subscales was confirmed by Cronbach’s α ≥ .70. Moreover, investigation of the validity of the Persian version of this questionnaire indicated a significant difference between the total mean score and the mean scores of the subscales in the 2 groups (P ≤ .001).^44,45

Spielberger’s anxiety scale was used to evaluate the participants’ anxiety. This scale consists of 40 questions, 20 related to state anxiety and 20 related to trait anxiety. The reliability of this scale was approved in the study by Agha Mohammadi et al conducted on 150 patients undergoing surgery. The reliability and validity indexes reported in that study are the bases for the present study.⁴⁶

After obtaining written informed consents from all the participants, TSH and prolactin experiments were requested for those who had obtained scores ≤22 in the FSFI to reject thyroid and prolactin disorders, which are the secondary causes of sexual dysfunction. The study participants were selected through convenience sampling and were randomly divided into 2 intervention groups and a control group. All the study groups had to consume the medications 1 hour before their sexual intercourse.

Elaeagnus angustifolia was purchased from the market and was identified by a botanist in the College of Pharmacy of Shiraz University of Medical Sciences. A sample of the plant was deposited in Shiraz School of Pharmacy Herbarium with voucher number PM811. Then, the plant was powdered using a special grinder and passed through a 60-mesh sieve. The obtained powder was then put in size zero capsules. Each patient was required to consume 4.5 g Elaeagnus angustifolia capsules in 2 divided doses (2 capsules every 12 hours) for 35 days. The women were also required to use the capsules during their menstrual cycles in order to determine the effectiveness of the plant.

The participants of the second intervention group had to consume 50 mg sildenafil citrate tablets 1 hour before sexual intercourse for 4 weeks. The effectiveness of this tablet is equal to 12 hours.⁴⁷ However, since the women did not use sildenafil citrate tablets during their menstrual periods, they had to be monitored for 35 days.

Finally, the control group participants were required to consume 2 placebos every 12 hours for 35 days. Placebo was made of starch and was completely similar to Elaeagnus angustifolia flower capsules. All the capsules were located in similar boxes encoded as A and B, and sildenafil citrate tablets were purchased from a pharmacy.

This study was single blind; the type of the intervention was unknown to the research population, but the pharmacist and the researcher were aware of the interventions due to the difference between Elaeagnus angustifolia flower and placebo capsules and sildenafil citrate tablets.

The study participants were followed through SMS twice a week and through phone contact once a week. After the intervention, FSFI and Spielberger’s anxiety scale were completed by the participants.

Finally, the data were entered into the SPSS statistical software (v. 18) and analyzed using paired t test, one-way ANOVA, and post hoc Bonferroni tests. P < .05 was considered as statistically significant.

Results

The mean age of the participants was 32.67 ± 5.05 years, and the highest frequency was related to 30- to 0-year-old age range (67.2%). Besides, the participants’ mean of marriage age was 21.59 ± 4.61 years, and the highest and lowest frequencies were related to below 20 years old (44%) and above 30 years old (4%) age groups, respectively. The mean length of marriage was 11.16 ± 6.45 years. Moreover, the mean age of the women’s husbands was 37.7 ± 6.51 years, with the highest frequency being related to above 30 years old age group.

The study results revealed no significant difference among the 3 study groups regarding TSH (P = .448) and prolactin (P = .179) levels. Also, the results of independent t test showed no significant difference among the 3 groups with respect to the mean score of state anxiety before the intervention (P = .67). However, a significant difference was observed in this regard after the intervention (P = .047). Furthermore, the results of paired t test demonstrated a significant difference in Elaeagnus angustifolia (P = .095) and control (P = .508) groups (Table 2).

Table 2.

Comparison of Mean of State Anxiety Before and After Intervention Between the Intervention and Control Groups.

State Anxiety	Elaeagnus angustifolia Flower Capsule Group (mean ± SD)	Sildenafil Citrate Group (mean ± SD)	Control Group (mean ± SD)	P Value
Before intervention	21.41 ± 5.99	22.15 ± 4.98	22.51 ± 6	.67
After intervention	2023 ± 6.01	20.1 ± 5.15	22.9 ± 6.1	.047
Chang rate	−1.18 ± 4.42	−2.04 ± 3.58	0.39 ± 3.8
P value	.095	.001	.508

The results of the independent t test indicated no significant difference among the 3 groups regarding the mean score of trait anxiety before (P = .794) and after the intervention (P = .096). Moreover, the results of the paired t test revealed a significant difference in the sildenafil citrate group before and after the intervention (P = .002), but not in the Elaeagnus angustifolia (P = .079) and control (P = .592) groups (Table 3).

Table 3.

Comparison of Mean of Trait Anxiety Before and After Intervention Between the Intervention and Control Groups.

Trait Anxiety	Elaeagnus angustifolia Flower Capsule Group (mean ± SD)	Sildenafil Citrate Group (mean ± SD)	Control Group (mean ± SD)	P Value
Before intervention	22.47 ± 9.5	23.07 ± 4.98	23.19 ± 4.94	.694
After intervention	21.18 ± 5.12	21.55 ± 4.83	23.41 ± 5.03	.096
Chang rate	−1.29 ± 4.42	−1.51 ± 3.02	0.22 ± 2.71
P value	.079	.002	.592

The results of the paired t test showed that the differences before and after the intervention were statistically significant in the sildenafil citrate group (P = .001), but not in the Elaeagnus angustifolia (P = .072) and control (P = .502) groups (Table 4).

Table 4.

Comparison of Mean of Total Anxiety Before and After Intervention Between the Intervention and Control Groups.

Total Anxiety	Elaeagnus angustifolia Flower Capsule Group (mean ± SD)	Sildenafil Citrate Group (mean ± SD)	Control Group (mean ± SD)	P Value
Before intervention	43.89 ± 11.7	45.22 ± 9.08	45.7 ± 10.6	.718
After intervention	41.41 ± 10.7	41.66 ± 9.71	46.32 ± 10.8	.058
Chang rate	−2.47 ± 8.45	−3.55 ± 6.3	0.61 ± 5.9
P value	.072	.001	.502

In addition, Pearson’s correlation coefficient revealed a significant reverse relationship between sexual function and anxiety mean scores (P < .001) in such a way that as the score of anxiety decreased, sexual function score increased.

Discussion

The results of the present study showed that sildenafil citrate table was effective in reduction of state and trait anxiety of married women aged between 18 and 40 years.

In this study, the mean levels of TSH and prolactin were 2.6 ± 1.07 and 10.05 ± 5.27, respectively, which were within the normal range. Hypothyroidism and hyperprolactinemia are among the secondary causes of sexual dysfunction. Atis et al reported a significant difference between women suffering from hypothyroidism and subclinical hypothyroidism and the control group regarding sexual function (P = .006).⁴⁸

According to the findings of the current study, a significant difference was observed in the sildenafil citrate group regarding state anxiety before and after the intervention (P = .001), but no such difference was found in the Elaeagnus angustifolia (P = .095) and control (P = .508) groups. Also, the results showed a significant difference in the sildenafil citrate group with respect to trait anxiety before and after the intervention (P = .002), while no significant differences were observed in this regard in the Elaeagnus angustifolia (P = .079) and control (P = .592) groups.

Sexual dysfunction is a complex, multifactorial problem affected by various physiological and mental factors. The individuals with sexual dysfunction are usually not mentally healthy and suffer from anxiety, depression, and lack of self-esteem. They are also twice as exposed to psychological changes requiring continuous and accurate follow-up. Therefore, providing these individuals with basic psychosomatic consultations is of utmost importance in improvement of their quality of life, interpersonal relationships, and self-confidence.⁴⁹

Philip et al investigated the relationship between sexual function and mental health in 70 women with rectal and anal cancer who had referred for treatment of their sexual dysfunction. In general, women’s normal sexual function is considerably disturbed after treatment of rectal and anal cancer, eventually affecting their mental health. The results of that study also indicated that women’s sexual dysfunction was accompanied by a wide range of mental disorders. In fact, sexual satisfaction showed reverse correlations with all the evaluated mental health indexes, namely, body image, anxiety, and cancer-specific posttraumatic disease (P < .001, r = −.45 to −.70).⁵⁰ In addition, Lin et al revealed a statistical relationship between sexual dysfunction and depression, anxiety, and physical symptoms in the patients suffering from major depressive disorder.⁵¹

In the current study, improvement of sexual dysfunction reduced the women’s anxiety, indicating improvement of their mental health. Evidence has disclosed that herbal medicines, such as ArginMax, ginseng, ginkgo biloba, and ethanol extract, are effective in improvement of sexual dysfunction^28,52,53 through increase of NO. NO is also among the compounds extracted from Elaeagnus angustifolia flower. In our study, consumption of Elaeagnus angustifolia flower capsule resulted in a decrease in the mean changes in state (−1.18 ± 4.42) and trait (−1.29 ± 4.42) anxiety; however, the differences were not statistically significant. Sexual stimulation leads to release of vasoactive neurotransmitters, such as NO, in women’s sexual organs. Besides, NO local liberation affects the central nervous system and spinal reflexes, which control sexual responses in transfer of nitrergic neurotransmitters.^54,55 It has been speculated that Elaeagnus angustifolia flower capsule increases NO and sexual stimulation. Thus, since NO leads to activation of soluble ganglion sylase and formation of cGMP, it prepares women to a great extent for maximizing their sexual responses by minimum testosterone and estradiol levels.⁵⁶ Hence, reduction of anxiety in the present research population might have resulted from improvement of sexual stimulations.

Previous studies have shown that the most common molecules used in the treatment of female sexual arousal disorder include alprostadil (prostaglandin E1), α-adrenoceptor antagonist, phentolamine, PDE5, and sildenafil citrate, which activate the NO-cGMP pathway.⁵⁷ The findings of several studies by Caruso et al^47,58 and other researchers^43,59,60 on women with sexual dysfunction have revealed the effectiveness of sildenafil citrate in one sexual dysfunction dimension. It seems that consumption of sildenafil citrate tablet, which is among PDE5 inhibitors, increases NO through prevention of cGMP catabolism, eventually resulting in relaxation of smooth muscles particularly in vaginal arteries, veins, and capillaries and clitoris. In this study, improvement of sexual dysfunction by sildenafil citrate might have been effective in reduction of anxiety.

A previous double-blind placebo-controlled study evaluated sexual function in 19 women suffering from spinal cord injury. The study women were randomly divided into sildenafil citrate and placebo groups. Vaginal congestion was measured using vaginal plethysmography. The results demonstrated a significant increase in mental arousal scores in the sildenafil citrate group (P < .01). Improvement of sexual function was still more significant when sildenafil citrate was accompanied by visual stimulation and a guide booklet. However, although increase of vaginal congestion was more significant in the sildenafil citrate group, the difference was not statistically significant (P = .07). Sipski et al also came to the conclusion that sildenafil citrate could relatively improve sexual dysfunction in the women with spinal cord injury.⁶¹ It should be mentioned that no pharmacological treatment methods have been proposed for female sexual arousal disorder in women.⁶² Therefore, other treatment methods particularly herbal medicine should be taken into account for the treatment of female sexual arousal disorder.⁶²

One of the limitations of the present study was that the participants might not have been serious in correct consumption of the medications. However, the necessity to accurately consume the medications was reminded by the researcher through contacting the participants weekly during the study period. Moreover, in case the participants did not act in accordance with the intervention protocol, they were excluded from the study and replaced by others. Another study limitation was that some questionnaire items were not clear enough, which was eliminated by the researcher’s sufficient explanations.

Conclusion

The findings of the present study revealed that sildenafil citrate led to a significant reduction in anxiety resulting from sexual dysfunction among the women referring to gynecology clinics. Although Elaeagnus angustifolia flower capsule also decreased the anxiety level, the difference was not statistically significant. Considering the limitations in available treatment methods for sexual dysfunction, although the current study results supported those of the previous studies, further studies with larger sample sizes are required.

This study aimed to compare the effects of Elaeagnus angustifolia flower capsule, sildenafil citrate tablet, and placebo. In case the effectiveness of this herbal supplement (Elaeagnus angustifolia) is approved, couples can be provided with a method with lesser complications so as to decrease the problems originating from anxiety resulting from sexual dysfunction.

Footnotes

Authors’ Note

This article is a part of Sanaz Zeinalzadeh’s thesis (Thesis Number: 91-6o16; IRCT: 201205219818N1).

Acknowledgments

The authors appreciate the Research and Technology Department of Shiraz University of Medical Sciences for financial support. The authors are grateful to Ms A. Keivanshekouh at the Research Improvement Center of Shiraz University of Medical Sciences for improving the English.

Author Contributions

The work presented in this article was carried out through collaboration between all authors. M. Akbarzadeh defined the research theme. M. Akbarzadeh M and S. Zeinalzadeh designed methods and experiments and prepared the first draft of the manuscript. A. Mohagheghzadeh and P. Faridi carried out supervision on drugs and placebo in the experiments. M. Sayadi analyzed the data. All authors have contributed to, seen, and approved the article.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors acknowledge financial support from the Research and Technology Department of Shiraz University of Medical Sciences.

Ethical Approval

This research project was approved by the local ethics committee of Shiraz University of Medical Sciences, and written informed consents were obtained from all the participants. Number of ethical leter: CT-91-6016.

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