Equol is produced when daidzein, a soy isoflavone, is metabolized by intestinal bacteria. It is said that approximately 50% of Japanese women produce equol. Equol has an estrogenic effect and, similar to estrogen, a link between equol and lifestyle-related diseases such as hypertension, diabetes and dyslipidemia, and menopausal disorders, has been reported [1]. In addition, some reports also have shown the effectiveness of estrogen as a treatment for lower urinary tract symptoms (LUTS) in women, including overactive bladder (OAB), urge urinary incontinence, and stress urinary incontinence which are induced by various lifestyle-related diseases as mentioned above. Furthermore, genitourinary syndrome of menopause (GSM), which results in LUTS due to urogenital atrophy caused by decreased secretion of sex hormones around menopause, has attracted attention in current clinical practice. In addition, estrogen replacement therapy is believed to improve LUTS by reducing urogenital atrophy. However, there have been no reports on the association between estrogenic equol and LUTS, including OAB. This study examined the association between the presence or absence of equol production and female OAB.

Female patients diagnosed with OAB at our hospital between April 2019 and December 2023 were included in this study. Patients were divided into two groups according to the presence or absence of equol production. Differences in patient background, such as age of onset, subjective symptoms of OAB, and other objective findings, such as voided volume, were examined retrospectively. Subjective symptoms were assessed using the Overactive Bladder Symptom Questionnaire (OABSS), with a urinary urgency score (Question 3) of at least 2 points, and a total OABSS score of at least 3 points was defined as an OAB. Patients with an obvious neurogenic lower urinary tract dysfunction or pelvic organ prolapse were excluded. We evaluated the equol production level using spot urine samples, and the equol level was determined by enzyme-linked immunosorbent assay. The cut-off value of urinary equol for the equol production was defined at 1.0 µmol/L.

The study included 84 patients: 39 (46.4%) in the equol-producing group and 45 (53.4%) in the equol-non-producing group. The age of onset of OAB was 63.7±11.2 years in the equol-producing group and 57.3±13.4 years in the non-producing group, with the age of onset significantly higher in the producing group (P=0.0211). The OABSS showed no difference in the daytime frequency or nocturia between the two groups. However, the urgency (3.44±1.23 vs 3.82±0.98: P=0.1600) and urgency incontinence (2.26±1.85 vs 3.00±1.75: P=0.0783) tended to be lower in the equol-producing group. In objective findings, there was no significant difference between the two groups regarding voiding volume (237.1±150.9 mL vs 183.4±97.8 mL: P=0.2947). The median age of onset of OAB in the patients was 63.5 [28- 83] years, which was used as the cut-off value for a similar study in the young onset and old onset groups. In the young group, 15 (32.6%) were equol-producing, and 31 (67.4%). Conversely, 24 (63.2%) were equol-producing in the older group. As the results,there were significantly more equol-producers in the older group than in the young group (P=0.0081). The older group had no significant differences in symptoms or voided volume between the equol-producing and non-producing groups. However, in the younger group, the OABSS scores at diagnosis were significantly lower for the equol-producing group than for the non-producing group, both in urgency (2.93±1.10 vs 3.94±0.89; P=0.0039) and urgency incontinence (1.53±1.77 vs 3.13±1.65; P=0.0074). Additionally, the total OABSS scores (7.13±3.11 vs 10.13±2.93; P=0.0033) were significantly lower in the equol-producing group. When the severity of OAB was classified as mild, with a total OABSS score of 5 or less; moderate, with a score between 6 and 11; or severe, with a score of 12 or more, the severity of OAB was significantly lower in the equol-producing group than in the non-producing group (mild: 40.0% vs 9.7%; moderate: 46.7% vs 48.4%; severe: 13.3% vs 41.9%, P=0.0349).

In this study, we found that individuals who produce equol had a significantly later onset of Overactive Bladder (OAB) and milder symptoms, as assessed by the Overactive Bladder Symptom Score (OABSS), compared to those who do not produce equol. Additionally, among patients with an earlier onset of OAB, those who were equol producers experienced less severe symptoms than non-producers. These findings indicate that exposure to equol may postpone the onset of OAB to a later age, and equol production plays a vital role in alleviating its symptoms. Equol exhibits effects similar to estrogen and is thought to help maintain the health of the urinary and reproductive systems in women, protect vascular functions, and reduce oxidative stress. Although exploring these various mechanisms of action in detail is beyond this study's scope, it is suggested that equol may contribute to preserving lower urinary tract function.

The presence or absence of equol production may affect the onset and severity of female LUTS, including OAB.

Usui, T.; Tochiya, M.; Uchiyama, S.; et al. Effects of natural S-equol supplements on overweight or obesity and metabolic syndrome in the Japanese, based on sex and equol status. Clin. Endocrinol. 2012, 78, 365–372.

Continence 12S (2024) 101610
DOI: 10.1016/j.cont.2024.101610