Effects of Glycine max (L.) Merr. soy isoflavone vaginal gel on epithelium morphology and estrogen receptor expression in postmenopausal women: A 12-week, randomized, double-blind, placebo-controlled trial
Introduction
Vaginal atrophy (VA) is a common condition in postmenopausal women associated with vaginal and/or urinary symptoms such as vaginal dryness, itching, discomfort and dyspareunia, dysuria, urinary urgency and frequency [1]. The disorder typically occurs in postmenopausal women, but can affect women of any age who experience a decrease in estrogenic stimulation of the urogenital tissues [2]. Sexual function and quality of life may also be reduced as a result of these changes [3].
According to The North American Menopause Society (NAMS), symptoms associated with vulvovaginal atrophy (VVA) affect 20–45% of midlife and older women, but this aspect of menopause is often overlooked and undermanaged, because only a minority seek medical help for the problem [4]. In contrast to vasomotor symptoms, which tend to improve over time even without treatment, VVA can be progressive and is less likely to resolve without intervention [4].
The primary goal of treating symptomatic VVA is to alleviate symptoms. First-line therapies include nonhormonal, long-acting vaginal moisturizers and low-dose vaginal estrogen, assuming no contraindications [4]. Despite the effectiveness of estrogen, concerns over side effects and safety have hindered its use by postmenopausal women. In recent years, phytoestrogen supplements have become attractive as safer alternatives, and their efficacy has been investigated in experimental and clinical trials [5], [6], [7], [8].
Isoflavones are the most studied of the phytoestrogens and some trials involving its oral form for treating climacteric symptomatology have shown no change in vaginal epithelium or endometrium [9], [10]. Similarly, topical preparations for the prevention and delay of skin maturation in postmenopausal women have shown satisfactory outcomes [11], [12].
Cytologic examination of vaginal mucosa from menopausal women shows a decreased proportion of superficial cells and an increased proportion of parabasal cells [13]. Also, the vaginal lining thins and vaginal pH increases from the normal 3.5–4.0 (which favors lactobacilli) to 6.0–8.0 (which favors pathogenic organisms) [14], [15].
Although cytohormonal analysis of the vaginal epithelium is well established as a method of evaluating oestrogenic influence, where maturation value (MV) can be calculated to express degree of vaginal atrophy as a numeric rating [16], in cytology analysis, only the exfoliated cells are studied. In order to gain a broader picture of the process of maturation of the vaginal epithelium a morphometric method should also be used.
Estrogen is a dominant regulator of vaginal physiology. Estrogen-receptor (ER) is present in the vaginal tissues of both premenopausal and postmenopausal women [17], [18]. The biological effect of estrogens is mediated by direct interaction with two ERs, ERα and ERβ. The ERs belong to the superfamily of steroid nuclear receptor transcription factors that activate binding to specific DNA sequences, called estrogen-responsive elements, on the promoters of the target genes [19].
Few studies investigating the effects of vaginal administration of isoflavones on vaginal atrophy symptoms are available [7], [20], [21] while no studies using the morphometric method as a means of assessing vaginal epithelium and ER expression in vaginal cells in postmenopausal women have been reported. The aim of the current investigation was to evaluate the effects of vaginal administration of isoflavones derived from Glycine max (L.) Merr. as a treatment option for vaginal atrophy, on the morphology and expression of estrogen receptors in vaginal epithelium of postmenopausal women.
Section snippets
Setting
The study commenced in July 2011 and was concluded in April 2013. The clinical trial was performed in accordance with the Declaration of Helsinki and International Standards of Good Clinical Practice (ICH-E6). The study protocol and patient informed consent form were approved by the Research Ethics Committee of the Irmandade da Santa Casa de Misericórdia de São Paulo hospital, in São Paulo – Brazil. All investigations were performed at this institution.
Study design
The double-blind, randomized,
Results
Of the 117 participants enrolled, 60 subjects remained after applying the inclusion and exclusion criteria. A total of 30 women received 1 gram of isoflavone vaginal gel 4% daily for 12 weeks and 30 women received 1 gram of placebo vaginal gel for the same period. In the placebo group, two women discontinued treatment due to lack of improvement and two subjects were lost to follow up. In the isoflavone group, one woman discontinued due to leucorrhea (Fig. 1). Patient baseline characteristics
Discussion
The effect of isoflavones derived from Glycine max (L.) Merr. in the treatment of vaginal atrophy by topical gel compared to placebo was evaluated. Systemic hormone therapy with natural estrogens is used for the relief of menopausal symptoms. However, a substantial proportion of women with urogenital complaints and changes in sexuality have no clinical improvement from systemic hormone treatment, where the combination of local treatment for relief of symptoms is required in this group [29].
Contributors
They were responsible for the clinical history, physical examination and treatment of the study participants, and also contributed to the writing of the paper, statistical tests and conclusions
Maria Antonieta L. Galvão da Silva (PhD) contributed to the cytological, morphological and immunohistochemical study.
Competing interests
None of the authors involved in this study have any form of conflict of interest.
Funding information
Funding for the entire study was conducted by researchers.
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