Serum Level of Vitamin D, Testosterone, Estrogen in Females with Sexual Dysfunction: A meta-analysis

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Introduction
Female sexual dysfunction (FSD) is known as problems observed by a female during any stage of normal sexual engagement, including physical pleasure, orgasm, interest, preference, and arousal [1].
FSD is a widespread issue that affects about 40% of women; however, there are some treatment options.It is a growing and widespread issue.Common symptoms of FSD include decreased vaginal lubrication, soreness and discomfort during intercourse, a decreased sense of desire, and orgasm problems [2].
Vitamin D has paracrine, endocrine, and autocrine activities.Sunlight, nutrition, and vitamin D supplementation are all sources of vitamin D [3].Hypovitaminosis D is linked to sexual dysfunction in healthy women and erectile dysfunction in males when other diseases are present [4].The primary sex hormone in males is testosterone.In men, testosterone is important in the formation of male reproductive tissues such as the testes and prostate, in addition to the development of secondary sexual features like body hair growth and increased muscle and bone mass [5].Androgens may have a role in the regulation of vaginal tissue physiology and female genital sexual arousal [6].Estrogen, or estrogen, is the predominant female hormone.In both males and females, estrogen levels are lower than androgen levels [7].Although estrogen levels in men are significantly lower than in women, estrogen plays important physiological roles in men [8].Estradiol and testosterone are both important steroid hormones for controlling female sexual desire [9].
Vitamin D deficiency affects other sexual disorders, like erectile dysfunction in male sexual dysfunction [10].Also, it was found by other studies that some dermatological diseases are exaggerated by vitamin D deficiency, as in alopecia areata [11] and vitiligo [12].

Subjects
This meta-analysis follows the PRISMA flow diagram and the guidelines of the Cochrane Handbook.

Eligibility Criteria
Inclusion criteria included: • Adult females aged between 20 and 45 years.
• Females suffering from sexual dysfunction according to FSFI score.

Exclusion criteria included:
• Patients with depression and diseases affecting Vitamin D level.
• Cases on antidepressant drugs.
• Cases that are not sexually active.

Information Sources
We searched PubMed, Scopus, Web

Data Collection
We collected data regarding: • The baseline demographics of included participants.

• Outcome endpoints which included
Vitamin D level in the serum • The third category involved data for assessing the likelihood of bias.The data collection process was conducted utilizing Microsoft Excel [14].

Risk of bias Assessment
Two authors utilized Cochrane's risk of bias tool for clinical trials to assess the risk of bias in the included papers [15].The tool evaluates patient randomization, allocation concealment & sufficient blinding across seven domains [16].Each domain is put to either "low", "unclear", or "high" risk of bias.

Main outcome and measures
All outcomes, including decreased vitamin D levels in female sexual dysfunction cases, decreased vitamin D levels in other sexual disorders such as erectile dysfunction in male sexual disorder, and decreased vitamin D levels in many dermatological diseases, such as vitiligo and alopecia areata, were formulated prior to data collection.

Analysis
We used Review Manager Software to do the meta-analysis for this study, which included both continuous and dichotomous outcomes.We used mean difference (MD) and 95% confidence interval (CI) to analyse continuous data.While dichotomous data were analysed using risk ratio (RR) and 95% CI, all data from different independent experiments were displayed as mean standard deviation [11].The students t-test method was used to compare two groups, and a one-analysis of variance (ANOVA) approach was utilised to compare the variance among at least three groups.
Statistical significance is described as a p value less than 0.05.

Results
A systematic review of one article discovered that hypovitaminosis D is involved in female sexual dysfunction; this meta-analysis revealed that vitamin D is significantly reduced in female sexual dysfunction cases compared to the control group, as well as in other sexual disorders such as erectile dysfunction in male sexual disorders and many dermatological diseases such as alopecia areata and vitiligo (Figure 1).

Figure1:
The PRISMA flow diagram of our literature search.

Conclusions and relevance
This systematic review and metaanalysis discovered that hypovitaminosis D plays a part in the etiology of female sexual

Discussion
FSD can have a significant impact on the quality of life of many women.It has been discovered that 40% of females in the United States experience sexual issues, which are frequently misunderstood and ignored.Female sexual dysfunction is difficult to diagnose since it is multifaceted [17].Calciferol is another term for vitamin D3, a fat-soluble vitamin found in a variety of foods and as a dietary supplement.It is also created endogenously from ultraviolet (UV) rays when they enter the skin and promote the process of its synthesis.
Testosterone is the primary male sex hormone, produced mostly by the testes [18].It's carried into the bloodstream by the protein sex-hormone-binding globulin (SHBG), and testosterone is a significant but mysterious female hormone [18].It operates directly as an androgen and also as an important precursor for the creation of estradiol; nevertheless, the management of testosterone production in women is unknown due to the lack of a feedback loop covering its production.In females, testosterone has physiological effects in both reproductive and non-reproductive tissues [14].Estrogen is the most important female sex hormone, and it plays important roles in both reproductive and non-reproductive tissues.Estrogen can be produced in nonreproductive tissues, for example, the liver, brain, bone, heart, and muscle, and this is consistent with the range of estrogen activities [7].
In Basson in which he concluded that there is no evidence of low androgen activity in females with low sexual libido [19].

Limitations
This study has numerous limitations, including the fact that it is a case-control study, which may be related to a retrospective nature and does not indicate causation.

Conclusion
This systematic review and metaanalysis propose that vitamin D plays a major role in the etiology of FSD and other sexual and dermatological diseases.
Understanding the possible factors and biological pathways involved in the etiology of female sexual dysfunction will help us develop effective treatments.

Conflicts of Interest:
The authors declare no conflicts of interest.
of Science, and Cochrane CENTRAL databases till April 2021 for related records.The research involves the following 4 articles: Vitamin D3 deficiency is associated with female sexual dysfunction in premenopausal women, Vitamin D and Male Erectile Function, Vitamin D insufficiency alopecia areata patients, Decreased circulatory levels of Vitamin D in Vitiligo.

2. 3 .
Search and Study Selection Interventional and observational studies included peoples with sexual dysfunction and depression disorders.There are three steps.The initial stage entailed transferring the results of electronic databases to a Microsoft Excel [4] sheet via EndNote Software [13].The second phase was carried out by two different authors and includes title and abstract screening as well as full-text examination of the articles put into the Excel sheet.Step 3 of the involved citations from step 2. In addition, we personally checked the references of the involved papers for any potential missing research.

Table 1 ) . Table 1 .
The relationship of Vitamin D3 and BDI score with FSFI score between the groups.