Muturitus, 13 (1990) 1-5
Elsevier Scientific Publishers Ireland Ltd. MAT 00602
Oral discomfort and hormone replacement therapy in the post-menopause A. Volw, Wqmtment
V. Lucenti’, A. Foraboscob, F. BoseW, A. Maietta Latessaa, P. Pozzo”, F. Petragliaa and A.R. Genazzan?
of Oketrics
and Gynaembgy and bDepmtment of Odontologv, University of Modena, Vio &I Pozzo 71, Ma&na (Italy)
(Receives! 28 June 1989, revision received 19 March 1990, accepted 22 March 1990)
We evaluated the incidence of oral discomfort in post-menopausal women and the efficacy of hormone repkement. therapy in patknts complaining of such symptoms. Two studies were performed. In the fm. we compared oral discomfort and oral mucosa smears in 47 patients receiving repkement therapy and in 40 untreated post-menopausal women. In the second, the efficacy of hormone qkanent therapy with oestriol vaginal cream (22 patients) or conjugated oestrogens plus norethkterone acetate (10 patients) was evaluated. In the first study, oral exfoliative cytology showed a similar maturation index and vohnne in both groups. In the second, hormone replacement therapy improved st. jective and objective symptoms in 12 out of 22 patients treated with oestriol and in 7 out of 10 patients treated with conjugated oestrogens plus norethisterone. These data suggest that oestrogen deficiency cao be considered a possible cause of oral discomfort in some post-menopausal patients and that oestrogen repkement therapy may improve subjective symptoms. (Key words: Oral discomfort, Post-menopause. Hormone replacement therapy)
Interest in the study of the effects of hormone repIacement therapy on the oral mucosa in the post-menopause was aroused by the observation that some patients suffer from oral discomfort during this period [l]. In the post-menopause the oral mucosa may show peculiar features, such as a dry and shiny appearance and a colour ranging from pale to bright pink. A decrease iu oestrogen plasma levels makes oral epithelial maturation difficult, leaving it incomplete and leading to atrophy [2]. Timonen [3] reported that oral cytology is related to low oestrogen plasma levels during the climacteric. Not all studies, however, agree on the correlation between oral cytology and low oestrogen levels in the post-menopause. Jacobs [4] did not observe any correlation between oral cytology and age. In view of these confIicti.ng data, the aim of the present study was to examine the incidence of s to: FVokssor An&ale Volpe. Departmat of Obstetrics and Gynaecology. University of Modala. Vii dcl Pozzo 71. Modena, Italy. 0378512281603.50 0 1991 Eisevier §cientific Publishers Ireland Ltd. Printed and Published in Ireland
2
oral discomfort in post-menopausal women and also the effects of hormone replacement therapy on the oral mucosa. Sabjeets and methods In our first trial we studied two groups of post-menopausal women who reported no subjective oral symptoms. The first group comprised 47 women, aged 52-58, who received hormone replacement therapy (HRT’) for at least 6 months (0.625 mg/day conjugated oestrogens for 21 days and 5 mg/day norethisterone from day 12 to day 21 of the treatment cycle). The second group of 40 post-menopausal women, the controls, received no hormonal therapy. Detailed histories were taken from all the subjects concerning past systemic diseases, dietary regimens and oral hygiene habits. In addition, they each underwent a gynaecological and a dental examination during which smears were prepared. A second study was carried out in 32 post-menopausal women, aged 50-57, who were complaining of dryness and/or burning sensations in the oral mucosa and also dysgeusia. These subjects also underwent a gynaecological examination as well as a dental examination and an oral exfoliative cytology assessment in order to rule out the presence of local irritants, such as excessive tartar deposits or poor dental prostheses which might cause oral discomfort. In all patients there was clinical evidence of hypotrophy or reduction of the free gum margin and widening of the distance between the cementoenamel junction and the mucogingival line. Ten of these 32 patients were treated with conjugated oestrogens 0.625 mg/day for 21 &ys plus norethisterone 5 mg/day from day 12 to day 21 for 3 cycles. The remaining 22 received oestriol vaginal cream 0.5 mg/day for 4 weeks, followed by 0.5 mg/day twice weekly for 2 months. When the 3 months of therapy were completed the dental examination and oral smear tests were repeated.
In the first trial, oral exfoliative cytology showed that the maturation index and volume were similar in both groups (Fig. 1). In the second trial, hormone replacement therapy improved subjective symptoms and the clinical appearance of the oral mucosa in 7 out of the 10 patients treated with conjugated oestrogens plus norethisterone and in 12 out of the 22 patients treated with oestriol vaginal cream. In the remaining 13 patients the objective and subjective symptoms remained almost unchanged. Moreover, the average oral cytology maturation volume in all 32 patients showed only a slight increase, which was not signitkant. However, taking into account the maturation and volume index in the 19 out of 32 patients who benefited from replacement therapy (7 treated with conjugated equine oestrogens plus norethisterone acetate and 12 treated with oestriol vaginal cream), a significant increase in the number of intermediate and superficial cells was observed (Figs. 2 and 3).
Fii. 1.
Maturation vohuneof oralmucosain 47 women during hormone replacement therapy and in 40 Controls.(m) treatedgroup.
untreated controIs. (0)
7a 60
50 Lo s 30 2c ia (I
fig. 2. Maturation volume of oral mucosa in 7 out of 10 patients who derived benefit frcPmconjugated oc~roga~s pIus noretkterone therapy. (a) Before therapy. (m) after therapy.
4
80
20,s 10 0
L
Fig. 3. Maturation volume of oral mucosa in 12 out of 22 patients who derived benefit from oestriol vaginal cream. (P) Before therapy. (m) after therapy.
Discussion The oralmucosa is in many ways similar to the vaginal mucosa. In fact, both have a pluristratified epithelium and a desquamative growth pattern. Although it is well known that vaginal epithelium is a marker of hormonal status, it is still debatable whether the oral mucosa exhibits the same pro??rties [4IO]. There is still also much controversy about the validity of oral cytology as an index of hormonal status in the post-menopause. Bercovici et al. [ll] did not find any correlation between oestrogen deficiency and oral cytology and considered oral discomfort in post-menopausal women to be due to local irritating factors rather than hormonal influences. On the other hand, evidence has accumulated suggesting a relationship between ovarian hormones @estrogens) and structural modifications (hyperplasia, hypertrophy, and/or atrophy) of the gingiva (2-121. Some studies (13,141 have demonstrated that oestrogens may affect cellular proliferation, differentiation and keratinixation [15] of the gingival epithelium. Oestrogens may stimulate the proliferation of gingival fibroblasts [16] and maturation of connective tissue, mainly through their influence on collagen turnover, by blocking its degradation [17,18]. Wardrop et al. [ 11reported that 43% of a group of patients with climacteric symptoms complained of oral discomfort, which improved after hormone replacement therapy. Furthermore, a form of chronic gingivitis accompanied by gingival pain and bleeding in the post-menopause is well known.
5
Because of the restricted number of patients studied our data are not cozxk;sive. In general, we did not see any significant difference between the oral cytology of the post-menopausal woman receiving replacement therapy and that of the contrds. We did observe, however, that some of the post-menopausal women suffered from oral dryness and burning and from dysgeusia. This may have been due to oestrogen deficiency, since we c?refuUy excluded patients in whom these symptoms could have been caused by loca! irritants. A consid&Ie percentage of the patients gained real benefits from hormone replacement therapy. We feel, therefore, that it is important to consider oestrogen deficiency as a possible cause of oral discomfort during this period of life.
1 2
3 4 5 6
Wardrop BW, Beade PC, Hailes J. Burger HG. Oral discomfort during the menopause. Maturitas198+6:286. Wingrove FA. Bdbunce of ovarian hormone situation on atrophy, hypertrophy and for desquamation of human gingiva in premettopausal and postmenopausal woman. J Periodontol 1979; 50: 445. ThIlOrICn !k Exfokted oral cells as indicators of estrogen stimulation. Odontol T 1964; 72: 324-333. JacobsA. C~mificafi~~ ia buccal smears. Br Dent J 1959; 106: 249-250. ziskin DE, M~dtou E. A 00mparistm of oral and vaginal epithelii smears. J Clin Endocrinol Metab 1% 8: 146-149. Jnss~mR. A cytol~&al study of the comification of the oral mucosa in women. Oral Surg 19% 3: 1516-1520.
7
Main DMG. Bitehie GM. Cyclic cbattges in oral smears from young menstruating women. Br J
8
Detmatol 1967; 79: 20-U). Croley TE. EpitbeliaJ changes in oral mucosa resulting from a variation in hormone stimulus. J
9 10 11 12 13 14 IS
16 17 18
Oral Med 197% 33: 3. of human gingiva in the menstrual cycle and menopause. Papic M, Glickman 1. Kem&zation WStUg1950;3:504-587. Trott JR. A desquamative eytologicaJ study of the gingiva and oral mucosa in women. J Perident 195% 29: 213-216. Bercovici B. Gran S, F5santy S. Vaginal and oral cytology of tbe menopause. Acta Cytologica 1985; 29: 805-809. El-Ashir GM, El-Kaftawy AM, Nash MF. Yonis N: Comparative study of the influence of pregnancy and oral eotttraeeptives on the gingiva. Oral Surg 1970; 30: 472. Graziauo V, D’Angclo M, Ferrara P. Histomorphologico~ -xxhBcation durin& treatmer’ with e. Minetva Stomatolog 1973; 26: 421. Abate G, Capuzai P, Covaes V, Stefzmini F. oral pathology in stomatologic patients with endocrittopatbies. Endocrmol Sci DeJla Costituzione 1968; 29~ 428. Wtttek S, Ahman K, Rapport SC, Gordon GG, Hagedoom S, Souzhren AL. Effect of progestins on attdro8en 4-3 ketosteroid-Sa-A-ring reductase system in rat oral mucosa. J Dent Res 1978; 57: 511. Beagrie GS. Observation on cell biology of gingival tissue of mice. Br Dent J 1966; 121: 417. Ft&upa H_ -tat studies on the effect of sex hormones on the proliferation Of cells derived from the gingival tissues in tissue culture. Shikwa Gaku Ho 1973; 71: 1214. Skosey JL, w E. Effect of esttadiol benzoate on the degradation of insoluble collagen
of
ynt skjn. EtuM&nology
1973; 93: 311.
Elsevier Scientific Publishers Ireland Ltd. MAT 00602
Oral discomfort and hormone replacement therapy in the post-menopause A. Volw, Wqmtment
V. Lucenti’, A. Foraboscob, F. BoseW, A. Maietta Latessaa, P. Pozzo”, F. Petragliaa and A.R. Genazzan?
of Oketrics
and Gynaembgy and bDepmtment of Odontologv, University of Modena, Vio &I Pozzo 71, Ma&na (Italy)
(Receives! 28 June 1989, revision received 19 March 1990, accepted 22 March 1990)
We evaluated the incidence of oral discomfort in post-menopausal women and the efficacy of hormone repkement. therapy in patknts complaining of such symptoms. Two studies were performed. In the fm. we compared oral discomfort and oral mucosa smears in 47 patients receiving repkement therapy and in 40 untreated post-menopausal women. In the second, the efficacy of hormone qkanent therapy with oestriol vaginal cream (22 patients) or conjugated oestrogens plus norethkterone acetate (10 patients) was evaluated. In the first study, oral exfoliative cytology showed a similar maturation index and vohnne in both groups. In the second, hormone replacement therapy improved st. jective and objective symptoms in 12 out of 22 patients treated with oestriol and in 7 out of 10 patients treated with conjugated oestrogens plus norethisterone. These data suggest that oestrogen deficiency cao be considered a possible cause of oral discomfort in some post-menopausal patients and that oestrogen repkement therapy may improve subjective symptoms. (Key words: Oral discomfort, Post-menopause. Hormone replacement therapy)
Interest in the study of the effects of hormone repIacement therapy on the oral mucosa in the post-menopause was aroused by the observation that some patients suffer from oral discomfort during this period [l]. In the post-menopause the oral mucosa may show peculiar features, such as a dry and shiny appearance and a colour ranging from pale to bright pink. A decrease iu oestrogen plasma levels makes oral epithelial maturation difficult, leaving it incomplete and leading to atrophy [2]. Timonen [3] reported that oral cytology is related to low oestrogen plasma levels during the climacteric. Not all studies, however, agree on the correlation between oral cytology and low oestrogen levels in the post-menopause. Jacobs [4] did not observe any correlation between oral cytology and age. In view of these confIicti.ng data, the aim of the present study was to examine the incidence of s to: FVokssor An&ale Volpe. Departmat of Obstetrics and Gynaecology. University of Modala. Vii dcl Pozzo 71. Modena, Italy. 0378512281603.50 0 1991 Eisevier §cientific Publishers Ireland Ltd. Printed and Published in Ireland
2
oral discomfort in post-menopausal women and also the effects of hormone replacement therapy on the oral mucosa. Sabjeets and methods In our first trial we studied two groups of post-menopausal women who reported no subjective oral symptoms. The first group comprised 47 women, aged 52-58, who received hormone replacement therapy (HRT’) for at least 6 months (0.625 mg/day conjugated oestrogens for 21 days and 5 mg/day norethisterone from day 12 to day 21 of the treatment cycle). The second group of 40 post-menopausal women, the controls, received no hormonal therapy. Detailed histories were taken from all the subjects concerning past systemic diseases, dietary regimens and oral hygiene habits. In addition, they each underwent a gynaecological and a dental examination during which smears were prepared. A second study was carried out in 32 post-menopausal women, aged 50-57, who were complaining of dryness and/or burning sensations in the oral mucosa and also dysgeusia. These subjects also underwent a gynaecological examination as well as a dental examination and an oral exfoliative cytology assessment in order to rule out the presence of local irritants, such as excessive tartar deposits or poor dental prostheses which might cause oral discomfort. In all patients there was clinical evidence of hypotrophy or reduction of the free gum margin and widening of the distance between the cementoenamel junction and the mucogingival line. Ten of these 32 patients were treated with conjugated oestrogens 0.625 mg/day for 21 &ys plus norethisterone 5 mg/day from day 12 to day 21 for 3 cycles. The remaining 22 received oestriol vaginal cream 0.5 mg/day for 4 weeks, followed by 0.5 mg/day twice weekly for 2 months. When the 3 months of therapy were completed the dental examination and oral smear tests were repeated.
In the first trial, oral exfoliative cytology showed that the maturation index and volume were similar in both groups (Fig. 1). In the second trial, hormone replacement therapy improved subjective symptoms and the clinical appearance of the oral mucosa in 7 out of the 10 patients treated with conjugated oestrogens plus norethisterone and in 12 out of the 22 patients treated with oestriol vaginal cream. In the remaining 13 patients the objective and subjective symptoms remained almost unchanged. Moreover, the average oral cytology maturation volume in all 32 patients showed only a slight increase, which was not signitkant. However, taking into account the maturation and volume index in the 19 out of 32 patients who benefited from replacement therapy (7 treated with conjugated equine oestrogens plus norethisterone acetate and 12 treated with oestriol vaginal cream), a significant increase in the number of intermediate and superficial cells was observed (Figs. 2 and 3).
Fii. 1.
Maturation vohuneof oralmucosain 47 women during hormone replacement therapy and in 40 Controls.(m) treatedgroup.
untreated controIs. (0)
7a 60
50 Lo s 30 2c ia (I
fig. 2. Maturation volume of oral mucosa in 7 out of 10 patients who derived benefit frcPmconjugated oc~roga~s pIus noretkterone therapy. (a) Before therapy. (m) after therapy.
4
80
20,s 10 0
L
Fig. 3. Maturation volume of oral mucosa in 12 out of 22 patients who derived benefit from oestriol vaginal cream. (P) Before therapy. (m) after therapy.
Discussion The oralmucosa is in many ways similar to the vaginal mucosa. In fact, both have a pluristratified epithelium and a desquamative growth pattern. Although it is well known that vaginal epithelium is a marker of hormonal status, it is still debatable whether the oral mucosa exhibits the same pro??rties [4IO]. There is still also much controversy about the validity of oral cytology as an index of hormonal status in the post-menopause. Bercovici et al. [ll] did not find any correlation between oestrogen deficiency and oral cytology and considered oral discomfort in post-menopausal women to be due to local irritating factors rather than hormonal influences. On the other hand, evidence has accumulated suggesting a relationship between ovarian hormones @estrogens) and structural modifications (hyperplasia, hypertrophy, and/or atrophy) of the gingiva (2-121. Some studies (13,141 have demonstrated that oestrogens may affect cellular proliferation, differentiation and keratinixation [15] of the gingival epithelium. Oestrogens may stimulate the proliferation of gingival fibroblasts [16] and maturation of connective tissue, mainly through their influence on collagen turnover, by blocking its degradation [17,18]. Wardrop et al. [ 11reported that 43% of a group of patients with climacteric symptoms complained of oral discomfort, which improved after hormone replacement therapy. Furthermore, a form of chronic gingivitis accompanied by gingival pain and bleeding in the post-menopause is well known.
5
Because of the restricted number of patients studied our data are not cozxk;sive. In general, we did not see any significant difference between the oral cytology of the post-menopausal woman receiving replacement therapy and that of the contrds. We did observe, however, that some of the post-menopausal women suffered from oral dryness and burning and from dysgeusia. This may have been due to oestrogen deficiency, since we c?refuUy excluded patients in whom these symptoms could have been caused by loca! irritants. A consid&Ie percentage of the patients gained real benefits from hormone replacement therapy. We feel, therefore, that it is important to consider oestrogen deficiency as a possible cause of oral discomfort during this period of life.
1 2
3 4 5 6
Wardrop BW, Beade PC, Hailes J. Burger HG. Oral discomfort during the menopause. Maturitas198+6:286. Wingrove FA. Bdbunce of ovarian hormone situation on atrophy, hypertrophy and for desquamation of human gingiva in premettopausal and postmenopausal woman. J Periodontol 1979; 50: 445. ThIlOrICn !k Exfokted oral cells as indicators of estrogen stimulation. Odontol T 1964; 72: 324-333. JacobsA. C~mificafi~~ ia buccal smears. Br Dent J 1959; 106: 249-250. ziskin DE, M~dtou E. A 00mparistm of oral and vaginal epithelii smears. J Clin Endocrinol Metab 1% 8: 146-149. Jnss~mR. A cytol~&al study of the comification of the oral mucosa in women. Oral Surg 19% 3: 1516-1520.
7
Main DMG. Bitehie GM. Cyclic cbattges in oral smears from young menstruating women. Br J
8
Detmatol 1967; 79: 20-U). Croley TE. EpitbeliaJ changes in oral mucosa resulting from a variation in hormone stimulus. J
9 10 11 12 13 14 IS
16 17 18
Oral Med 197% 33: 3. of human gingiva in the menstrual cycle and menopause. Papic M, Glickman 1. Kem&zation WStUg1950;3:504-587. Trott JR. A desquamative eytologicaJ study of the gingiva and oral mucosa in women. J Perident 195% 29: 213-216. Bercovici B. Gran S, F5santy S. Vaginal and oral cytology of tbe menopause. Acta Cytologica 1985; 29: 805-809. El-Ashir GM, El-Kaftawy AM, Nash MF. Yonis N: Comparative study of the influence of pregnancy and oral eotttraeeptives on the gingiva. Oral Surg 1970; 30: 472. Graziauo V, D’Angclo M, Ferrara P. Histomorphologico~ -xxhBcation durin& treatmer’ with e. Minetva Stomatolog 1973; 26: 421. Abate G, Capuzai P, Covaes V, Stefzmini F. oral pathology in stomatologic patients with endocrittopatbies. Endocrmol Sci DeJla Costituzione 1968; 29~ 428. Wtttek S, Ahman K, Rapport SC, Gordon GG, Hagedoom S, Souzhren AL. Effect of progestins on attdro8en 4-3 ketosteroid-Sa-A-ring reductase system in rat oral mucosa. J Dent Res 1978; 57: 511. Beagrie GS. Observation on cell biology of gingival tissue of mice. Br Dent J 1966; 121: 417. Ft&upa H_ -tat studies on the effect of sex hormones on the proliferation Of cells derived from the gingival tissues in tissue culture. Shikwa Gaku Ho 1973; 71: 1214. Skosey JL, w E. Effect of esttadiol benzoate on the degradation of insoluble collagen
of
ynt skjn. EtuM&nology
1973; 93: 311.
