Purpose/Background: Many investigators reported that pharmacological treatment of female sexual dysfunction (FSD) has been a promising field yet to be explored. The purpose of this pilot study was to investigate the efficacy and safety of a topical cream containing small concentrations of three vasodilators with different mechanisms of action in treating FSD.
Methods: In this randomized, controlled pilot trial, premenopausal (n = 30) and postmenopausal (n = 30) cases of 21- to 62-year age range with FSD were allocated randomly into 15 given placebo or 15 given active cream in each group. The women included had FSD for more than a 6-month duration and a total score of Female Sexual Distress Scale-Revised of at least 15. Assessing sexual function by measuring female sexual function index (FSFI) during five clinic visits, one at the end of baseline week and at the end of each week of the 4-week treatment period. The primary end point was changed from baseline FSFI total scores to week 4 treatment. Secondary end point included the changes from baseline arousal, desire, orgasm, and satisfaction scores to week 4 treatment.
Findings/Results: The sexual problem reported by patients was orgasmic or/and arousal disorders. In premenopausal cases, active cream led to a high significant increase inmean change FSFI total score fromthe baseline to week 4 compared with placebo (1.7 ± 1.886 vs 13.35 ± 4.646, respectively; P < 0.0001). Greater improvement of mean change of orgasm and arousal domain score was also observed (0.3 ± 0.45 and 0.35 ± 0.39 vs. 2.66 ± 0.63 and 1.87 ± 0.168, respectively; P < 0.0001). In postmenopausal cases, there were significantly greater improvements with active cream in all sexual functions compared with placebo cream (P < 0.0001). In triple cream, mean change of FSFI total score, orgasm domain score, and arousal
score domain were 14.85 ± 6.33, 1.87 ± 0.168 and 2.66 ± 1.182, whereas in the placebo cream, they were 1.54 ± 2.1,0.7 ± 0.76 and 0.22 ± 0.44, respectively. Meanwhile, orgasm scores increased significantly after the use of
placebo cream. No serious adverse effects were reported during treatment.
Implications/Conclusions: The results of the pilot trial suggest that topical cream containing small concentrations of three vasodilators may act synergistically, and was effective in improving arousal, orgasmic, and satisfaction disorder with a safer profile for premenopausal and postmenopausal women with FSD. Further studies are recommended to be conducted using a large number of non-depressive and depressive patients.

Breakthrough infections have been reported in fully vaccinated persons. Furthermore, rebound symptoms have been reported following the new FDA granted emergency use to combat SARS-CoV-2. Glycyrrhizin (GR) and boswellic acids (BAs) combination has been shown to have highly successful actions against COVID-19 in our recent clinical trial. However, the study is limited by the small sample size, and therefore, the aim of this article is to comprehensively evaluate recent evidence on  the efficacy of GR and BAs in preventing the development of COVID-19 in patients with mild and moderate infections and in preventing post-COVID-19 cognitive impairment, which is the most important symptom after recovery from Covid-19 disease. We have reviewed and discussed information published since the outbreak of the COVID-19 pandemic until July 2022 on preclinical (in vivo, in vivo and bioinformatics) and clinical studies related to the antiviral, anti-inflammatory and immunomodulatory activity of Gr and BAs. Sixteen studies were performed to determine the efficacy of GR against SARSCoV- 2. Ten studies were used primarily for in vitro and in vivo assays and six used molecular docking studies. However, the antiviral activity of BAs against SARS-CoV-2 was determined in only five studies using molecular modeling and bioinformatics. All these studies confirmed that GR n and BAs have strong antiviral activity and can be used as a therapeutic agent for COVID-19 and as a protective agent against SARS-CoV-2. They may act by inhibiting the main protease SARS-CoV-2 (Mpro) responsible for replication and blocking spike protein-mediated cell entry. Only seven rigorously designed clinical trials regarding the usefulness of GR, BAs or their combinations in the treatment of COVID-19 have been published as of July 2022. Although there is no clinical study regarding the treatment of cognitive impairment after COVID-19 that has been published so far, several preclinical and clinical studies have demonstrated the potential effect of GR and BAs in the prevention and treatment of cognitive impairment by inhibiting the activity of several molecules that activate inflammatory signaling pathway. In conclusion, the findings of our study documented the beneficial use of GR and BAs to treat SARS-CoV-2 and its variants and prevent post-COVID cognitive impairment. However, it warrants further studies with a larger randomized sample size to ensure that the studies have sufficient evidence of benefits against COVID-19 and post-COVID-19 symptoms.