Real‑world performance and safety of vaginal ovules in reducing the vaginal symptoms associated with vulvovaginal atrophy and postmenopausal sexual dysfunction

**Background** Vulvovaginal atrophy (VVA), also termed genitourinary syndrome of menopause, is a common condition in postmenopausal women due to declining estrogen levels. It leads to thinning of the vaginal epithelium, reduced lubrication, and symptoms such as vaginal dryness, dyspareunia, dysuria, and itching. These symptoms significantly impair quality of life and sexual function. Estrogen therapy, while effective, carries risks including thromboembolism, stroke, and potential stimulation of hormone-sensitive cancers. Non-hormonal alternatives are needed. Halova is a medical device in ovule form containing sodium hyaluronate, marigold extract, vitamin E, aloe vera oil, and other ingredients designed to hydrate, soothe, and re-epithelialize the vaginal mucosa. This study aimed to evaluate its real-world performance and safety.

**Methods** This was an open-label, multicenter, non-randomized, real-world evidence study conducted in Romania between March and July 2022. A total of 249 female participants (aged 18-70 years, Caucasian) with clinical manifestations of vaginal dryness, perimenopause, VVA, menopausal disorder, or vaginal prolapse were enrolled. Exclusion criteria included psoriasis, vitiligo, plantar ulcers, lipoid necrobiosis, granuloma annulare, and vulvar or cervical cancer. Participants were divided into two groups: 179 received Halova ovules as monotherapy, and 70 used Halova ovules in combination with vaginal lubricants (polytherapy). The ovules were administered intravaginally once daily for 10 days. Data were collected at baseline and after 30 days. Primary outcome was tolerability; secondary outcomes included clinical performance (vaginal dryness, dyspareunia, dysuria), vaginal pH, endometrial thickness (by transvaginal ultrasound), and patient satisfaction (5-point Likert scale). Statistical analyses used Fisher's exact test and Mann-Whitney U test, with p<0.05 considered significant.

**Key Results** - Clinical performance: In the monotherapy group, 84.35% of patients rated treatment as 'excellent'; in the polytherapy group, 95.71% rated it as 'excellent' or 'highly effective'. - Vaginal pH: Normal pH was achieved in 75% of monotherapy and 84% of polytherapy patients. - Dyspareunia: 72% of monotherapy patients reported absent dyspareunia vs. 48% in polytherapy; 52% of polytherapy patients reported mild dyspareunia. - Endometrial thickness: 'Absent' thickness was noted in 76% (monotherapy) and 78% (polytherapy); 'mild' in 20% each; 'moderate' in 4% and 2%, respectively. - Dysuria: 64% of monotherapy and 78% of polytherapy patients reported absent dysuria. - Vaginal dryness: 82% of monotherapy and 80% of polytherapy patients reported no vaginal dryness. - Patient satisfaction: 94.38% of monotherapy patients rated treatment as 'excellent'. - No adverse reactions were reported.

**Clinical Implications** Halova ovules demonstrated significant efficacy in reducing the core symptoms of VVA—vaginal dryness, dyspareunia, and dysuria—while restoring normal vaginal pH and maintaining endometrial safety. The high patient satisfaction and absence of adverse events support its role as a safe, non-hormonal alternative for managing postmenopausal vaginal symptoms, particularly in women with contraindications to estrogen therapy (e.g., breast cancer survivors). The study's real-world design enhances generalizability, though limitations include lack of a control group, short follow-up (30 days), and heterogeneity of the sample. Future research should assess long-term efficacy and safety, including in special populations such as pregnant women.