Serum 17β-estradiol and oral dryness feeling in menopause

doi:10.4236/health.2011.35046

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Vol.3, No.5, 258-262 (2011)

doi:10.4236/health.2011.35046

Health

Serum 17β-estradiol and oral dryness feeling in

menopause

Farzaneh Agha-Hosseini1*, Iraj Mirzaii-Dizgah2

1Department of Oral Medicine/Dental Research Center, Dentistry School, Tehran University of Medical Sciences, Tehran, Iran;

*Corresponding Author: [email protected]

2Department of Physiology, School of Medicine, AJA University of Medical Sciences, Tehran, Iran; [email protected]

Received 21 January 2011; revised 18 February 2011; accepted 27 February 2011.

ABSTRACT

The aim of this study was to compare serum

17β-estradiol of menopausal women with/without

Oral Dryness (OD) feeling, and evaluate the re-

lationship between serum 17β-estradiol and

severity of OD feeling. A case-control study was

carried out on 70 selected menopausal women

aged 40 - 77 years with or without OD feeling (35

as case, 35 as control) conducted at the Clinic

of Oral Medicine, Tehran University of Medical

Sciences. Xerostomia inventory (XI) score was

used as an index of OD feeling severity. The

serum 17β-estradiol concentration was meas-

ured by an enzyme immunoassay kit (ELISA).

Statistical analysis of Student’s t-test and

Spearman correlation coefficient was used. The

mean serum concentration of 17β-estradiol was

significantly lower in case than control. There

was a significant negative correlation between

XI score and concentration of 17β-estradiol in

menopausal women (r = –0.311, P = 0.004). It

seems that there is a negatively slight correla-

tion between OD feeling severity and serum

17β-estradiol in menopausal women.

Keywords: Menopause; Oral Dryness Feeling;

17β-Estradiol; Serum

1. INTRODUCTION

Life expectancy for women has increased significantly

during the last decade, and most women spend one third

of their lives after the menopause. Menopause is a nor-

mal developmental stage in a woman’s life, marking the

permanent cessation of menstruation [1]. It is the result

of irreversible changes in the hormonal and reproductive

functions of the ovaries [2]. It is a retrospective diagno-

sis usually made after 12 months of amenorrhea. Meno-

pause is accompanied by a number of characteristic physi-

cal changes; some of which occur in the oral cavity [3].

Oral dryness feeling or xerostomia is a subjective

sensation. It is associated with an unpleasant feeling in

the mouth and throat [4]. This complaint is more preva-

lent in menopausal women on medication, and is quite

common also in those without disease or drug usage,

unrelated to lowered salivary flow rates [5-8].

It has been suggested that changes in estrogen and

progesterone play a major role in the development of

some forms of gingival disease [9]. It seems that oral

soft tissues are sensitive to changes in female sex steroid

blood levels. The decrease in estrogen levels during

menopause is thought to affect the oral epithelial matu-

ration process, leading to thin and atrophic epithelium

[10]. It has been shown that hormone replacement ther-

apy can relieve oral discomfort in menopausal women,

further suggesting a role for female sex hormones in the

maintenance of oral tissues [11]. Our previous study has

also shown that the level of stimulated salivary 17β-

estradiol concentration is lower in menopausal women

with OD feeling, and there is a negative correlation be-

tween OD feeling severity and stimulated whole saliva

17β-estradiol [5].

After complain of caries and periodontal problems,

the most complain of people who referred to oral medi-

cine department of Tehran University of Medical Sci-

ences is dry mouth feeling. To relive their problem, con-

secutively studies have been designed. The purpose of

this study was to evaluate whether the serum 17β-estra-

diol level correlates with severity of OD feeling, and to

compare serum 17β-estradiol of menopausal women

with/without OD feeling.

2. METHODS AND MATERIALS

2.1. Subjects

The Ethics Committee of Tehran University of Medi-

F. Agha-Hosseini et al. / Health 3 (2011) 258-262

259259

cal Sciences (TUMS), Iran, approved the study protocol.

Informed consent was obtained from all participants.

A total of 105 menopausal women were asked to par-

ticipate in a case-control study, conducted at the Clinic

of Oral Medicine, TUMS. The participants were aged

between 40 and 77 years, had not had a menstruation

cycle for at least 24 months, and were not taking any

medication at the time of the study. Smokers, obese pa-

tients (body mass index > 30), patients with systemic

diseases (including Sjogren’s syndrome), oral candidi-

asis, or with a bad oral health condition and periodontal

disease were excluded. Of the 105 potential participants,

20 were excluded from the study based on these criteria

(13 were eliminated owing to periodontal pocket depths

more than 3 mm in multiple sites, 5 were excluded for

obesity and 2 for smoking). The remaining women were

asked to answer a questionnaire with a list of symptoms

associated with xerostomia (Table 1). Thirty five an-

swered affirmatively to at least one of the questions re-

lated to xerostomia [12,13], and formed the case group;

in fact, all the participants in the case group answered

affirmatively to at least 3 of the questions. Thirty-five

who did not answer affirmatively to any of the questions

in Ta b l e 1 formed the control group. The remaining 15

were excluded in order to match case and control groups

on the basis of age and duration of menopause. The 15

who were eliminated were done so without knowledge

of the assay data; only the demographical factors were

viewed with blinding to the assay data.

Each participant also answered another questionnaire

so that we could assess the severity of xerostomia Table

2. Xerostomia inventory (XI) score was determined as

the severity of dry mouth feeling [14]. The scores of

responses were added to provide an XI score for each

individual (the minimum possible score was 11 and the

maximum possible score was 55).

2.2. Sample Collection

Stimulated and unstimulated whole saliva were col-

lected under resting conditions in a quiet room between

9 a.m. and 12 p.m. (midday), and at least 2 hours after

the last intake of food or drink. Unstimulated salivary

samples were obtained by expectoration in the absence

of chewing movements. For pre-stimulation, the women

chewed a piece of paraffin of standard size. After 60

seconds of pre-stimulation, the participants were asked

to swallow the saliva present in the mouth. Thereafter,

whole saliva, stimulated by the same piece of paraffin,

was collected over a period of about 5 minutes. Stimu-

lated and unstimulated whole saliva were collected into a

pre-weighed and dry plastic tube. By subtracting the

empty tube weight from the saliva filled one, saliva

sample weight was determined to calculate the salivary

Table 1. Questionnaire used for selection of subjects with

xerostomia (oral dryness feeling).

Serial

Number Questions

1 Does your mouth feel dry when eating a meal?

2 Do you have difficulties swallowing any foods?

3 Do you need to sip liquids to aid in swallowing dry foods?

4 Does the amount of saliva in your mouth seem to be reduced

most of the time?

5 Does your mouth feel dry at night or on waking?

6 Does your mouth feel dry during the daytime?

7 Do you chew gum or use candy to relieve oral dryness?

8 Do you usually wake up thirsty at night?

9 Do you have problems in tasting food?

10 Does your tongue burn?

Response options: yes and no

Table 2. The xerostomia inventory (XI).

Serial

Number Questions

1 I sip liquids to help swallow food.

2 My mouth feels dry when eating a meal.

3 I get up at night to drink.

4 My mouth feels dry.

5 I have difficulty in eating dry foods.

6 I suck sweets or cough lozenges to relieve dry mouth.

7 I have difficulties swallowing certain foods.

8 The skin of my face feels dry.

9 My eyes feel dry.

10 My lips feel dry.

11 The inside of my nose feels dry.

Response options: Never (scoring 1), Hardly (2), Occasionally (3),

Fairly often (4), Very often (5)

flow rate. The flow rate was calculated in grams per

minute, which is almost equivalent to milliliters per

minute [6].

Venous blood was collected from each participant in

the morning under resting conditions in a quiet room,

between 9 a.m. and 12 p.m. The specimens were ob-

tained by venipuncture, collected in 10 ml glass vacuum

tubes without additive, and allowed to clot. The blood

was then centrifuged (2000 g, 10 min) and the serum

were separated and stored at −70˚C for later determina-

tion of 17β-estradiol concentration.

F. Agha-Hosseini et al. / Health 3 (2011) 258-262

260

2.3. 17β-Estradiol Concentration Assays

Serum 17β-estradiol concentration was analyzed by

ELISA technology using commercially available kits

(DRG Instruments GmbH, Germany). Wells coated with

anti-estradiol polyclonal rabbit antibody. Standards were:

0; 25; 100; 250; 500; 1000 and 2000 pg/ml. the OD was

read at 450 nm with microtiterplate reader. The range of

the assay was between 0 - 2000 pg/ml.

2.4. Statistical Analysis

For statistical analysis, the data are presented as a

mean ± SEM. The 2-tailed Student unpaired t test was

used to compare serum 17β-estradiol level between case

and control groups.

The Spearman correlation analysis was used to iden-

tify any correlation between XI score and the serum

17β-estradiol. P less than 0.05 was considered statisti-

cally significant.

3. RESULTS

The characteristics of case and control participants are

shown in Ta ble 3. There were no significant differences

between two groups in BMI, age or years after meno-

pause.

The Student’s unpaired t test showed that there was a

significant difference between the groups concerning

unstimulated whole salivary flow rate. It was lower in

the case (0.26 ± 0.12) than in the control (0.33 ± 0.01; P

= 0.001) groups. However, No significant difference was

found between the case (0.33 ± 0.02) and control (0.37 ±

0.01; P = 0.07) groups regarding stimulated saliva flow

rate.

Student t test showed that there was a significant dif-

ference in serum concentration of 17β-estradiol between

the groups (Figure 1). It was significantly lower in case

compared with the control (P = 0.01). Coefficient of

variations (CV) was 0.30 for control group and 0.41 for

case group.

Spearman correlations were performed to see if rela-

tionship existed between severity of OD feeling (XI

score) and serum 17β-estradiol. There was a negative

significant correlation between XI score and serum

17β-estradiol concentration (r = –0.311, P = 0. 004).

4. DISCUSSIONS

Oral dryness is a major complaint for many elderly

individuals, and is strongly associated with the meno-

pause [6,15,16]. The exact mechanisms that cause sensa-

tion of OD in menopausal women have not been firmly

established. However, there are reports on amelioration

of these symptoms by estrogen treatment [8]. In this

Table 3. Clinical characteristics of menopausal women with/

without oral dryness (OD) feeling.

Clinical characteristics

(mean ± S.D.)

Women without

OD feeling

Women with

OD feeling

Age (years) 56.55 ± 6.31 55.87 ± 6.55

Years-since-menopause 10.0 ± 6.9 10.1 ± 7.6

Body mass index

(BMI, Kg/m2) 24.2 ± 2.5 24.8 ± 2.1

Xerostomia inventory

(XI) score 12.21 ± 1.2 30.24 ± 6.14

Figure 1. Comparison of serum concentration of 17β-estradiol

(means ± SEM) between menopausal women with oral dryness

feeling and healthy individuals as determined by unpaired stu-

dent’s t-test, *P = 0.001.

study, the relationship between serum 17β-estradiol level

and OD in menopausal women was investigated.

Our data showed that serum 17β-estradiol concentra-

tion is significantly lower in menopausal women suffer-

ing from oral dryness. It also appears that OD severity

correlates with serum 17β-estradiol concentration. It has

been shown that the composition of saliva in menopausal

women is estrogen dependent [17]. In addition, hormo-

nal replacement therapy has been reported to reduce the

complaints of dry mouth feeling resulting in improved

oral wellbeing. On the other hand, oral discomfort is a

common symptom of menopause, it often occurs without

overt clinical signs, and it frequently resolves during

appropriate hormone replacement therapy [8,15,16,18,

19]. It seems that a positive relationship exists between

ovarian hormone modifications and changes in the oral

mucosa, and sex hormone withdrawal might be a cause

in incidence of oral dryness feeling in menopausal

women [10]. Gingival tissue is known to be sensitive to

changes in the hormonal balance, especially to changes

in female sex steroids [9]. It has been suggested that

changes in hormone levels and types (predominantly

F. Agha-Hosseini et al. / Health 3 (2011) 258-262

261261

estrogen and progesterone) play a great role in the de-

velopment of some forms of gingival or periodontal dis-

ease [20]. Clinical reports of gingival enlargement con-

current with the onset of puberty and during pregnancy,

or gingival atrophy and surface desquamation during

menopause, have led some investigators to regard the

gingival as a secondary target organ for the direct action

of female sex hormones [9]. Also, human gingiva has

been showed to metabolize estrogens [21].

Consistent with our previous studies on stimulated

whole salivary 17β-estradiol [5], and serum and saliva

progesterone [22] the results showed that subjects with

OD had significantly lower serum 17β-estradiol concen-

tration in menopausal women with OD feeling compared

with the control group. In addition, a negative correla-

tion between serum 17β-estradiol level and severity of

OD in menopausal women was also observed. Therefore,

it is possible that there is a relationship between serum

17β-estradiol level and OD feeling in menopausal

women.

We also found that unstimulated, but not stimulated

whole saliva flow rate, was significantly lower in meno-

pausal women with OD feeling, in comparison with

women without OD feeling, which was consistent with

our previous studies [5,6,22,23]. It can be concluded that

menopausal women with OD feeling suffer from re-

duced salivary flow rate in unstimulated conditions.

However, it may alleviate in a stimulated state.

Our research had not planned for day-to-day collec-

tion of serum sample, because we anticipated and ex-

perienced resistance from the study participants espe-

cially in the control group, so we took only one sample.

There were other limitations to this study, e.g., this was a

cross-sectional study and longitudinal studies may find

similar or different results.

5. CONCLUSIONS

It seems that there is a slight negative correlation be-

tween OD feeling severity and serum 17β-estradiol in

menopausal women.

6. ACKNOWLEDGEMENTS

Research conducted with Grant from Tehran University of Medical

Sciences, Tehran, Iran. The authors declare that there is no conflict of

interests.

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