key: cord-0872729-bzkmf125
authors: Mohammed, Ghada Farouk; Saad, Hany Mohammed
title: Severe COVID-19 has Low Testosterone, Estrogen Levels, and Impaired Sexuality
date: 2022-05-03
journal: Sexologies
DOI: 10.1016/j.sexol.2022.03.002
sha: d6204ce0193b64b73794a1b3cb3d314bf2eb7b78
doc_id: 872729
cord_uid: bzkmf125

For assessing whether women with and without COVID-19 differed with regard to female genital self-image, sexual function and hormonal profile. Female genital self-image being assessed with the female genital self-image scale (FGSIS) and Female Sexual Function Index (FSFI) and laboratory investigations. The study had revealed significant differences in all domains of the FSFI except pain between the cases and the controls. The study had demonstrated significant differences in all domains of the FGSIS between the cases and the controls. The study had shown significant decline in the post COVID-19 serum levels of total testosterone (TT), free testosterone (FT) and estradiol (E) between the two groups (p<0.05). Positive correlations between serum TT, FT, E and FGSIS domains and total score of FGSIS in the cases were observed.

Introduction:

The World Health Organization (WHO) demonstrates that Coronavirus 2019 causes severe acute respiratory syndrome with severe acute respiratory coronavirus 2 (SARS-CoV-2) from humans to humans, worldwide (Park, 2020; . The disease of SARS-CoV-2 infection was considered as a pandemic on 11 th March 2020, due to rapid spread and deaths in many countries (Park, 2020) . This highly contagious disease characterized with fever, dry cough, muscle aches, fatigue and shortness of breath. Currently, measure available for managing COVID-19 is covering the mouth and nose with mask, hand washing and maintaining social distance, can decrease burden of disease, stay-at-home and even a mandatory quarantine(Considerations Relating to Social Distancing Measures in Response to COVID-19 -Second Update, 2020; Wilder-Smith & Freedman, 2020) .

Female Sexual dysfunction is a common distressing disorder that affects the quality of lives. This affects female sexual interest/arousal disorder, hypoactive sexual desire disorder, genito-pelvic pain/penetration disorder and female orgasm disorder(The Impacts of Isolation Measures Against SARS-CoV-2 Infection on Sexual Health, n.d.) . COVID-19 can affect sexual health and function (Shaeer et al., 2020) .

Female genital self-image is an imperative pillar of sexual esteem, satisfaction, behavior, performance and psychosocial health (Mori et al., 2020; Pampati et al., 2020) . Because sexual health is an imperative pillar of people's well-being, it is thought that sexual contact will be affected negatively (Anis et al., 2011) . Social measures taken in facing this contagious disease will change the social interactions and sexual life behaviors (Schiavi et al., 2020) . Being contacting with COVID-19 also J o u r n a l P r e -p r o o f FGSIS in Patients with raised the negative effects on the sexual function and genital self-image of women.

Therefore, sexual and reproductive health should also be involved in the pillar of COVID-19 management. Universal health coverage should include women. Thus, we aimed in the current prospective cohort study to investigate the effect of COVID-19 on female sexual function and female genital self-image as well as serum levels of total testosterone (TT), free testosterone (FT) and estradiol (E).

The current prospective study was conducted on women who contracted COVID-19 and admitted to a tertiary hospital from January (2021) to March (2021).

The study was conducted in accordance with the Helsinki Declaration guidelines (1964) after receiving institutional review board approval. All participants provided written informed consent and were between 18-60 years old. Any case invited to join the present study was diagnosed of having COVID 19 after the results of the reverse transcription polymerase chain reaction (RT-PCR) test of pharyngeal and nasal swabs performed due to suspected COVID-19 infection. The criteria of the COVID-19 guidelines in determining the severity of COVID-19 stated by Xu et al (2020 ( )(Xu et al., 2020 were strictly followed up. The guidelines of strengthening of observational studies in epidemiology (STROBE) were adhered to ( Figure 1 ).

Sexually active women who had finalized the management protocol, discharged and had no past history of sexual dysfunction.

Exclusion criteria of the patients J o u r n a l P r e -p r o o f

Any patient who had a history of incontinence, being pregnant, on a current management protocol for COVID-19, having a history of pelvic organ prolapses, being on hormonal contraception or intrauterine devices or contraception implants, antidepressant medication or having a chronic illness that impairs sexual performance or hormones as (PCOS or any other form of hyperandrogenism) were excluded. All psychological elements were excluded using the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, published by the American Psychiatric Association.

Inclusion criteria of the controls They were age matched healthy sexually active females in a committed relationship not on hormonal contraception and not on any long term medications for any chronic illness. After computer-based randomization, as controls, 100 healthy volunteer women were used. Controls were selected from close associates of the cases, such as friends and relatives who were attending with the patients or healthy escorts of dermatology patients attending the dermatology outpatient clinic.

Between the specified time intervals, 462 women were admitted to the hospital.

Following the exclusion criteria, the remaining cases totaled 250, with only 135 completed the study ( Figure 1 ). All of them hospitalized for two weeks and completed the treatment protocol. 100 healthy volunteer women served as controls. The structured interview took place for the patients at the isolation hospitals and compared with medical reports. One month later; the patients were contacted via telephone to attend the second structured interview. All the participants were subjected to: Detailed Scale (ArFGSIS) (Mohammed & Hassan, 2014) were used to evaluate the sexual function and the genital self-image for the participants & laboratory investigations.

All participants filled in the questionnaires by themselves and results were where compared to medical records. In the ovulatory period (D8 to D15) a blood sample of 5 ml was obtained from each participant in order to assess sex hormone binding globulin (SHBG), TT, FT and E. The sensitivity of the assays was expressed as a minimal amount of the hormones distinguishable from the zero sample with 95% probability and the intraassay and inter-assay coefficients of variation for TT, FT, E and SHBG.

All individuals had performed blood tests in the same laboratory, using the same technique, at the same (approximate) time. This was carried out in the middle of the menstrual cycle (days 8-15). Blood was drawn from all women between 0800 and 1200 and stored at -20 o C for a period of 1-30 days until assayed.

For data analysis, SPSS software system version 25 (SPSS Inc, Chicago, IL, USA) was used. The quantitative data were presented as mean, standard deviation (SD), while the qualitative data were presented as percentages and frequency. The Kolmogorov-Smirnov was used to verify the normality of the variables distribution.

The paired t-test was used to compare data with a normal distribution, while the Wilcoxon signed ranks test was used to compare data that did not have a normal distribution. ANOVA test was used to compare data means of two or more groups. A median (minimum-maximum) was used for data that did not show the normal distribution. P<0.050 was considered significant. The Mann-Whitney test was used to compare continuous data. The Kruskal-Wallis test was used to assess the independent effects of multiple categorical variables because a standard distribution of the data could not be assumed. Testing mean 1=mean 2 (versus ≠), Calculating power for mean 1=mean 2+difference α=0.05 Assumed standard deviation=4. Target power is 0.9. Actual power 0.910232

The biographic, anthropometric, hematological and basic biochemical characteristics of the study population summarized in table 1 and 2. The groups were matched for age, BMI, smoking and duration of marriage without significant differences. Interestingly, the study had shown a significant decline in the frequency of sexual intercourse/week in the cases compared to the controls p˂0.05 (Table 1) .

There were significantly lower mean values of WBC, lymphocytic count, total protein and albumin (3.9±1.3, 0.91±0.2, 5.9±0.5 and 2.5±0.1, respectively) among study group than control group (6.1±1.1, 1.12±0.5, 7.1±0.2, and 2.9±0.2), p˂0.05 (Table 2) . (42±11, 12.7±11.3, 246±36.8, 22±1.8, and 24±2.1, respectively), p˂0.05 ( Table 2) .

All of the patients' and controls' SHBG levels were within normal ranges (33-97 nmol/l). Also, post COVID-19 serum levels of TT, FT and E showed significant decreasing differences versus controls (p<0.05) (Table 3) .043) and total score (11.1±0.7, 9.2±0.5, 6.4±0.3, p=0.02) according to the severity of COVID-19 (Table 5) .

Correlation of different FSFI domains with the total score on the FGSIS revealed a significant correlation with desire, lubrication, orgasm, and satisfaction domain (pvalues < 0.05); desire (r=0.015), arousal (r=0.505), lubrication (r=0.021), orgasm (r=0.012), satisfaction (r=0.041), and pain (r=0.202). So, the genital self-image was significantly as affected as sexual function.

In the current study, women who contracted COVID-19 had a significant decrease in the frequency of sexual intercourse, as well as a significant decrease in all domains of the FSFI except the pain domain, when compared to the controls. This significant decline can be attributed to significant declines in the serum levels of TT, FT and E as well as the negative impact of the lock down measures imposed by the pandemic situation. Also, this may be attributed to the cytokine storm and multiple organ failure induced by COVID-19 [Tang et al., 2020; Mehta et al., 2020; Jose & Manuel, 2020; Wright, 2020; Iba et al., 2020] . In the same context, Li et al (2020) post COVID-19 compared to the baseline and was lower than that in the controls. The discrepancy in the results of desire and arousal in our cases can raise the debate and substantial confusion in literature between either merging desire and arousal in a single entity (Meston et al., 2020) or dealing with them as distinct disorders. (Meston et al., 2020; Parish et al., 2019; Reed et al., 2016) In contrast, Yuksel and Ozgor (2013) found that estradiol positively affected the sexual desire especially during mid-cycle peak. (Roney & Simmons, 2013) The present study is one of a few studies that had demonstrated a potential impact of COVID-19 on serum levels of TT, FT and E in females affected by COVID-19 and their correlations with the severity of COVID-19.

On the one hand, an early Chinese study demonstrated similar finding as it revealed that women with low estrogen levels had more severe infection with COVID-19(Ding et al., 2020) . This can be explained by the fact that ovarian injury may be induced directly by COVID-19 binding to the angiotensin converting enzyme 2 (ACE2) J o u r n a l P r e -p r o o f

receptor and entering the cell through transmembrane serine protease 2 (TMPRSS2), leading to a cytopathic effect mediated by local replication of the COVID-19 [Jing et al., 2020] . This may also be induced by the severe illness in the form of multiple organ failure and cytokine storm theory that may happen during COVID-19 infection [Tang et al., 2020; Mehta et al., 2020; Jose & Manuel, 2020; Wright, 2020; Iba et al., 2020] .

On the other hand, the current study had shown that mild and moderate cases The perception of one's own genital appearance is a fundamental selfperception that influences one's ability to have meaningful sexual experiences. (Amos & McCabe, 2016) There is a link between positive genital self-image and positive sexual function, according to research. 11,29-32 Furthermore, genital self-image was considered as a tool for predicting a woman's behavior as her genital system was examined (Pakpour et al., 2014 ) Solati et al.(2005 , on the other hand, concluded that infertile women's lack of self-confidence could lead to lower sexual satisfaction and, as a result, lower scores on the Genital Self-image Scale. (Solati et al., 2006) We found that women after COVID-19 has lower total FGSIS scores than normal healthy women (8.4±0.4, and 14.1±0.9; respectively), which were statistically and clinically different. It is an important concern, however, because women with COVID-19 have an increased risk of sexual complications, which may be due to hormonal imbalance. (Berg & Denison, 2012) And Female sexual function is found to be strongly related to female genital self-image. (Mohammed & Hassan, 2014) According to research, women with higher levels of genital satisfaction are more sexually active and engage in more sexual activity than women with lower levels of satisfaction. (Rowen et al., 2018) This research has some limitations. Because this was an exploratory cross-sectional study, no conclusions about causation could be drawn.

We, on the other hand, used a validated, reliability-tested scale, trained clinic staff, multivariate analyses, and a large sample size.

There is a potential link between COVID-19 and total testosterone, free testosterone and estradiol through which it negatively impacts sexual function Totally, 150 participants agreed to join the study with 135 women completed the study and 15 refuse to continue. 100 healthy women were included as controls.

The structured interviews were conducted after 1 month of discharging. The Arabic version of the Female Sexual Function Index (FSFI) and the Arabic version of Female Genital Self Image Scale (FGSIS) were used to evaluate the sexual function and the genital self-image for the participants. 

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