The Effect of a Soy Rich Diet on the
Vaginal Epithelium in Postmenopause:
A Randomized Double Blind Trial

This section is compiled by Frank M. Painter, D.C.
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FROM:   Maturitas. 2003 (Aug 20); 45 (4): 241–246 ~ FULL TEXT

L.M. Chiechi, G. Putignano, V. Guerra, M.P. Schiavelli, A.M. Cisternino, C. Carriero

Department of Obstetrics and Gynecology III,
University of Bari,
Piazza Giulio Cesare II,
Bari 70124, Italy.

BACKGROUND:   A traditional asiatic phytoestrogen-rich diet is associated with a lower incidence of estrogen-dependent cancers and clinical consequences of postmenopausal estrogen deficiency. First Wilcox in 1990, showed an increase of the vaginal cell maturation with phytoestrogens on postmenopausal women, but this has not been confirmed in some subsequent studies.

METHODS:   In this study, we analyzed the effects of a 6–month soy-rich diet on the vaginal epithelium of asymptomatic postmenopausal women in a randomized clinical trial. 187 women were recruited for the study and divided into three groups: a phytoestrogen rich diet group; a hormonal replacement group, and a control group. A vaginal sample for hormonal cytology was taken before and at the end of the study, and sent unnamed to a cytologist.

RESULTS:   The karyopycnotic index (KI) increased significantly in the diet group and in the HRT group but not in the control group. The maturation value (MV) had an identical trend to the KI.

CONCLUSION:   We conclude that a soy rich diet is efficacious in increasing the maturation indices of vaginal cells. This effect could be a useful marker of the efficacy of a dietary intervention with phytoestrogen rich foods, and should be considered during preventive interventions against menopausal effects and vaginal atrophy.

From the FULL TEXT Article:


The lack of estrogens characterizes post-menopausal condition and is often associated with several disorders, including vasomotor symptoms, atrophic vaginitis, osteoporosis and cardiovascular disease. Accumulating evidence indicates that consumption of a phytoestrogen-rich diet alleviates menopausal symptoms [1–3], exerts favorable effects on post-menopausal osteoporosis [4] cardiovascular diseases [5], and is associated with a lower incidence of hormone-depending tumors, including breast cancer [1, 6]; among dietary phytoestrogens, isoflavones of soy seem to have the most beneficial effects. [7–10]

In the present randomized double blind trial, we investigated the effect of a soy rich diet on the vaginal epitelium in menopausal women; we also compared this effect of our diet with that of the HRT. Such a comparison has never been published, to our knowledge.

Study design and methods

      Study population and statistics

The design and methods of the present study were described previously. [11]

Participants included 187 healthy postmenopausal asymptomatic women aged 39–60, living in the Bari area, Southern Italy. All women gave written informed consent and the University of Bari Ethics Committee approved the study. Inclusion criteria included spontaneous menopause since at least 6 months and with FSH–30 IU/1 and E2B/20 pg/ ml or with bilateral ovariectomy; exclusion criteria were age –60, heavy drinkers, treatment with HRT, cholesterol-lowering, antiosteoporotic or other interfering drugs (i.e. tibolone), diabetes, history of cancer, in vegetarian or macrobiotic diet, presence of menopausal symptoms requiring therapy.

Dietary intervention has also been described in the previous paper; briefly, women in the diet group were invited to continue their usual diet, only adding a soy food serving every day (e.g. soymilk, miso soup, tofu, tempeh, or soybeans) and changing two meals twice a week with two meals of the menu of the study based on phytoestrogen rich foods; the aim of this intervention was to provide an isoflavone intake of at least 20–30 mg/day that is the average consumption among Asian women. [12, 13] The other groups had instructions to continue their habitual diet; all groups received instructions to avoid any change in their own habitual lifestyle and physical activity. Control group received no placebo.

Compliance to diet was assessed by measuring urinary daidzein levels in samples from a pool of morning urine collected daily for 14 consecutive days during the fifth month of the Study. [11] Hormonal profile (FSH and estradiol), height, smoking and drinking habits, education, and sedentariness, were evaluated only at baseline. Weight, body mass index (BMI), waist to hip ratio, karyopycnotic index (KI) and maturation value (MV) were evaluated at baseline and after 6 months. The use of both KI and MV was chosen because they both characterize the hormonal action on the vagina, but in a different way: the KI, giving the percentage of the cells with pycnotic nucleus is a more sensitive index for the superficial cells; the MV is instead useful to examine vaginal maturation when the vaginal epithelium is low. [14]

FSH and estradiol levels were measured by Ready PackTM tests (Chiron Diagnostic Corporation, East Walpole, MA, USA) with a chemiluminescence method on ACS analyzer: Centaur (Chiron Diagnostic Corporation). Urinary daidzein excretion values were measured by gas chromatography, after enzymatic hydrolysis with Helix Pomatia, solid phase extraction and HPLC purification. Vaginal smears for hormonal evaluation were taken from the upper third of the vagina and a quantitative analysis provided the KI and the MV (0/% parabasal cells/0.5/% intermediate cells/1.0/% superficial cells); vaginal slides were read separately by two expert medical cytologists who were unaware of which group was paired. Of 108 slides, 15 (16.2%) had too few cells to count and were not included in the calculations.

The analysis of variance (ANOVA) was used to detect the differences recorded in the different groups for each variable at baseline; the Kruskal– Wallis test has been used where necessary; we used a linear regression model to analyze the variations of the single indices (KI and MV) between sixth month and baseline values adjusted for BMI, age, months since menopause, FSH, E2. In the regression linear model, we used the following variables: BMI, age, months from menopause, FSH, estradiol for controlling the effects of each single variable on the variation of the KI and MV. The statistical significance was performed at 0.10. Stata Corp 2001 STATA Statistical Software: Release 7.0. College Station, TX: Stata Corporation was used in the statistical analyses.

Table 1

Table 2

Table 3

Table 4

Baseline characteristics of subjects in the study are reported in Table 1.

Controls show significant higher levels of KI at baseline than intervention groups; this is not of easy explanation; the high drop out probably introduced some bias; for example at the end of the study the women of the control group showed a greater BMI than diet and HRT groups (29.09 vs. 25.1 and 25.8, respectively).

According to the food frequency diaries, women in the diet group consumed approximately 47 mg/ diet of isoflavones, largely from soy milk. [11] The content of each isoflavone is shown in the Table 2. The good compliance to the diet in this group is shown by the high levels of urinary daidzein; this was 3114.6 ng/ml in the diet group versus 91.4 ng/ ml in the control group and 124.07 ng/ml in the HRT group.

The biggest increase of MV and KI has been obtained in the HRT group; these indices increased with statistical significativity in the diet group too, but not in the control group (39.1 in the HRT group vs. 12.6 in the diet group vs. 3 in the control group and 34.3 in the HRT group vs. 15.5 in the diet group vs. 0.7 in the control group, respectively) (Tables 3 and 4).


Phytoestrogens are diphenolic compounds with structural similarities to natural and synthetic estrogens and antiestrogens [15] acting as estrogen agonists and producing estrogen-like effects; they are plant-derived compounds that comprise several classes; among these the most potent are the isoflavones, widely present in the soybean subfamily of the Leguminosae.

Daily consumption of soy is followed by a significant increase of phytoestrogens in the serum of postmenopausal women. [16]

In the present study, we assessed the ability of a soy rich diet, because of the high content in isoflavones, to affect vaginal epithelium; it was the minor aim of the Menfis study, a clinical trial planed to assess the efficacy of a phytoestrogen rich diet on a long term effects of the menopause. [11] First Wilcox in 1990 [17], showed an increase of the vaginal cell maturation with phytoestrogens on postmenopausal women, and other authors found an estrogenic effect on vaginal cytology in animals [18–20] or in postmenopausal women [21] and vaginal dryness [22, 23], but the vaginal cell maturation has not been confirmed in some subsequent studies. [1, 4, 16, 24–27]

The vagina is covered by a mucosa with a Malpighian pluristratified epithelium with marked sensitivity to sex steroids, particularly to estrogens, even weak or little active on the upper genital part such as estriol; this specific action of natural estrogens is due to the presence of specific receptors [28] that make it the most sensitive marker for the morphological changes by estrogen substances. Due to the presence of the phenolic rings isoflavones have the ability to bind to estrogen receptors [29, 30] and exert the biological responses evoked by physiological estrogens; also on vaginal parameters genistein behaved as an agonist [31]; dose-finding study demonstrated this estrogenic effect of phytoestrogens on vaginal cytology even if this estrogenic potency is weak compared with that of estradiol and is proportional to estrogen receptor-binding capacity [32]; this weak estrogenicity or the short duration of receptor binding could explain the different behavior on the endometrium where we have no proliferative effect. [11–31]

The positive estrogenic effect on vaginal cells found in our study is probably to attribute to prolonged exposure to dietary phytoestrogens, the first time to our knowledge. We had a high drop out in the diet group because soy products are not usual components of the diet in our populations, and this could have introduced some bias; however our data seem to show quite clearly the estrogenic effects of the dietary phytoestrogens on vaginal epithelia of postmenopausal women indicating that vaginal cells seem to require a prolonged exposure to dietary estrogens to exert proliferative changes. [10] Because KI is the percentage of superficial cells found in the total population of the squamous cells examined and the MV is the total score of superficial cells and half of the intermediate cells [33] KI seems a more sensible marker of the action of phytoestrogens; in the study of Baird [21] the overall maturation index did not differ between women in dietary interventions and controls; but the difference became significant if superficial cells were examined; we report similar results.

Dietary phytoestrogens may modulate the consequences of the postmenopausal estrogen deficiency state, as it happens for asiatic populations that use these foods; our data are promising and important in preventing postmenopausal vaginal atrophy by dietary interventions; moreover vaginal cytology could be an useful tool to assess the estrogenic effects of dietary soy.


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