Periodontal aspects in menopausal women undergoing hormone replacement therapy
Aspectos periodontales en mujeres menopáusicas con terapia hormonal sustitutiva

 

Joaquín Francisco López Marcos ⁽¹⁾, Silvia García Valle ⁽²⁾, Ángel Agustín García Iglesias ⁽³⁾

(1) Doctor. Médico Estomatólogo. Prof. Asociado de la Facultad de Medicina y Odontología
(2) Licenciada en Farmacia
(3) Prof. Titular del Departamento de Obstetricia, Ginecología y Pediatría. Facultad de Médicina. Universidad de Salamanca

Address:
Joaquín F. López Marcos
C/ Isaac Peral 10-24, 2ºH
37004-Salamanca
Telf: 923 25 03 25
E-mail: jflmarcos@usal.es

Received: 29-02-2004. Accepted: 1-08-2004

 

 

INTRODUCTION

Current importance and concern about HRT issues is due to the high incidence of periodontal diseases related to affectation of the gingiva and periodontal bone. This increase is governed by the increase in life expectancy, the scientific evolution of medical knowledge and the increased educational and cultural levels of society. Women in particular may undergo a decrease in bone mass(1) during menopause (2), affecting sites such as the alveolar and jaw bones, which secondarily produces periodontal-gingival-tooth disease, bringing us closer to the possibility of being able to avoid and/ or treat the sequelae of this disease.

Increasing numbers of women are now using Hormon Replacement Therapy (HRT) and estrogens for replacement therapy during menopause (3), including: oral administration, estrogen-containing dermal patches and tibolone(4). The loss of bone density (5) in menopausal women can be documented using techniques such as X-ray-based densitometry (6) and since menopause is associated with a pattern of accelerated bone loss (7) it may also indicate the existence of bone mass loss from the alveolar and jaw bones, subsequently affecting the marginal gingiva and the periodontium(8). Assessment of the severity of periodontal disease can be achieved by measuring the loss of periodontal ligament attachment and the loss of interproximal alveolar bone; other measures include, the depth of the probings, the existence of supra gingival plaque, bleeding upon probing and the presence of calculi.

The present study aims to provide new information that may clarify the controversial points and to facilitate its application in periodontal disease. Here, we analyzed the effect that menopause, and especially estrogen deprivation, can have on the oral and dental health of women, mainly referring to the characteristics of the gingiva and the periodontium and checking whether the existence of gingival recession, pain, tooth mobility and pocket formation might allow us to evaluate the degree of reduction in bone mass in menopausal women.

PATIENTS

The present study addressed postmenopausal women. In order to develop this project, a randomized multicentric study was carried out with the following population design and methodology.

1- SAMPLE SELECTION:

Patients were menopausal women undergoing hormone replacement therapy who had gingival and periodontal disturbances.

2- SAMPLE SIZE:

A population comprising 210 patients, all of them in menopause due to physiological causes, to premature ovarian failure, or to surgical castration, were selected. 20 patients were excluded from the study due to immunodeficiency, endometrial, ovarian or breast cancer, chronic hepatic failure or convulsive disorders.

The final sample, which exceeded the initial forecast of the estimation of the size of the sample, comprised 190 patients distributed in two groups. One group (n=134) received HRT while the other one (n=56) did not receive any treatment.

3- STUDY POPULATION:

The patients were women of 40 to 58 years old with a mean of 49.6 years who had a gynecological history of depressive mood associated with sleep disorders, vasomotor instability (hot flashes) and trophic alterations to the vulva or vagina. In order to rule out breast and uterine disorders, all women were subjected to both mammography and ultrasound exploration.

4- STUDY PROCEDURE:

The treatments with HRT were indicated by the respective gynecologists. Patients undergoing HRT with estrogen-containing patches received a combined treatment (dermal patches in combination with orally administered low-dose progestogen). Two groups were formed:

1.- Women receiving estrogen-containing dermal patches.

2.- Women who, knowing the risks and benefits of this therapy, had decided to reject this option but had agreed to an evaluation of their oral status by dentists.

Blood samples were taken in order to monitor the hormone replacement therapy. The menopausal women were controlled by the stomatologist at the beginning of the therapy, and then followed up and reevaluated over 6 months to one year after the beginning of treatment. This allowed homogeneous and comparable data collection.

METHOD

A.- GYNECOLOGIC PROTOCOL. The patients underwent the following procedures: gynecologic examination, cytology, pelvic echography and mammography, all results lying within the normal ranges. The patients received HRT because of their menopausal symptoms. A gynecologic protocol was established for data collection: the initials of the patients, age, contraception used, type of menopause, menopausal symptoms, age of onset of menopause, general habits and general diseases.

B.- ODONTOSTOMATOLOGIC PROTOCOL. Patients presenting any oral or dental disturbances (tooth mobility, marginal gingival inflammation, and pain) were explored by the stomatologist according to the following exploration guidelines:

Anamnesis : Patients were asked about the existence of previous dental treatments, previous periodontal treatments, oral hygiene measures, oral habits, dental pain and type of HRT being used.

Physical exploration: The following characteristics were evaluated:

Tooth mobility: assessed according to the degree of tooth mobility.

Grade 0: No mobility
Grade 1: Mobility of the dental corona between 0.2-1 mm measured horizontally.
Grade 2: Mobility of the dental corona greater than 1 mm measured horizontally.
Grade 3: Mobility of the dental corona, also in the vertical direction.

Gingival recession: In teeth presenting this problem, the existence of gingival recession was measured with a dental probe and expressed in mm from the enamel-cement limit to the free gingival margin.

Depth of probing: The distance from the gingival margin to the bottom of the gingival pocket was measured with a conventional periodontal probe, HU-Friedy^® PCP 11, graduated at 3, 6, 8 and 11mm with a presssure no greater than 25 gr. The depth of the pocket was measured for each tooth, only the highest value found for each tooth being recorded in the clinical records.

Depending on the data obtained and the nature of the variables studied, the best possible statistical method applicable to this situation was evaluated.

Study of between-observer reproducibility was carried out on periodontal pockets of 15 previously unidentified patients by two dentists other than the author in 15 cases. The results obtained were analyzed according to McNemar's test.

Informed consent to participate in the study was obtained from all patients.

C.- STATISTICAL METHOD.

A basic description of the socio-demographic variables of the patients using means and standard deviations for the quantitative variables and percentages for the qualitative variables was performed.

In order to analyze the efficacy of the treatment, upon considering the qualitative variables an analysis of variance of the 2 factors -where one of them was the repeated measurement (10) - was performed. The aim of this was to compare the efficacy of the treatment before and after administration, taking into account the group the patient belonged to (no HRT, HRT in patches).

For the response variables considered dichotomic qualitative variables, the McNemar test was used. For the qualitative variables with more than two categories, a generalization of the McNemar test for m×m contingency tables, called the Stuart-Maxwell test (13), was used.

Statistical significance was set at the 5% and 1% levels (at p<0.05 and p<0.01).

RESULTS

A- DESCRIPTION OF THE GENERAL SOCIO-DEMOGRAPHIC AND CLINICAL VARIABLES.

The sample comprised 190 menopausal women with the following characteristics (Table 1):

Age. The range was from 40 to 58 years, with a mean of 49.6 and a standard deviation of 3.7.

Most of the patients used different contraceptive methods (oral contraceptives, intrauterine devices or barrier methods).

Physiological menopause was the most frequent cause (128 patients out of 190 cases studied, representing 67.49 % of the cases). 36 and 26 patients had premature ovarian failure or had undergone surgical castration, respectively.

Most of the patients included in the sample had common menopausal symptoms, hot flashes being the most frequent symptom (109 patients). 16 of the patients (8.4%) had several symptoms at the same time.

In the women of our sample, menopause occurred at ages between 40 and 53 years, with a mean and standard deviation of 48.5±3.9 years, respectively.

Regarding the general life habits of the patients, 59 patients (31.1%) were smokers while 9 were regular drinkers.

Diabetes (11.6%) and hypertension (10%) were the most frequently found general diseases among these patients.

In most cases, the subjects had received one or more dental treatments. Only 16.8 of the patients reported never having received dental care.

62.6% of the patients had received tartar removal treatment and more than 10% of the patients had not received any treatment at all.

With respect to oral hygiene, surprisingly 31 patients (16.3%) reported never practicing any oral hygiene at all.

The most common feature in relation to oral habits was to have no habit at all. Clenching was the most frequent oral habit found (20.5%) and only two patients reported more than 1 type of habit.

B- OUTCOME OF THE RESPONSE VARIABLES PAIN

The analysis confirmed the absence of statistically significant differences between the two groups studied before and after the treatment, the p-values being 0.077 and 0.481, respectively.

On the first and second visit, the group of patients not receiving HR therapy reported that their pain had not subsided but, instead, had persisted or become even worse. Fifty percent of the cases who had not experienced pain before began to suffer from some kind of pain: i.e, 33% of the patients started to experience acute localized pain, 10% experienced dull pain, and 3.3% felt both kinds of pain.

In patients receiving HRT administered in patches, the localized acute pain disappeared in 12.5% of the cases and did not worsen in any of the cases. Also, dull and constant pain disappeared in 16% of the cases although 4% of the patients began to feel both types of pain (Fig.1).

TOOTH MOBILITY

The results obtained for tooth mobility in the patients not receiving HRT were considered statistically significant (p= 0.035). Of the patients presenting no tooth mobility, 71.5% evolved to grade 1. Of that presenting grade-1 tooth mobility, 56% of the cases evolved to grade 2 and 3% evolved to grade 3, and of that presenting grade-2 tooth mobility, 37.5% of the cases evolved to grade 3. None of the cases showed any reduction or disappearance of tooth mobility.

The results obtained for the group receiving HRT in patches were not significant, with a p-value of 0.066. Strikingly, of the patients presenting grade-1 tooth mobility, 33.3 % of the cases evolved to no mobility, while 6.6% worsened to grade 2. Of those with presenting grade-2 tooth mobility, 50% of the cases evolved to grade 1 and 6.4% of the cases evolved to grade 3 (Fig.2).

GINGIVAL RECESSION

The results obtained for the women not receiving HRT were not significant, with a p-value of 0.167. In the group not presenting recession on the first visit, a recession of 0 to 1 mm was observed on the second visit in 58% of the cases, while of those presenting a recession of 0 to 1 mm, 66.7% evolved to a 1-3 mm recession, and of those presenting a recession of 1 to 3 mm, 15% of the cases evolved to a recession greater than 3 mm, and only 3% of the cases showed a reduction in recession to between 0 and 1 mm. In the patients with a recession greater than 3 mm, no changes were observed during the second visit (Fig.3)

The results obtained for the patients treated with dermal patches were not statistically significant, with a p-value of 0.126. In the group starting with a recession of 0 to 1 mm, in 40 % of the cases an evolution to no recession was observed, while only 5% of the cases evolved to a recession of 1-3 mm, and of those with an initial recession of 1 to 3 mm, in 27% of the cases a gingival recession of 0 to 1 mm was observed, and only 6% of the cases evolved to a recession greater than 3 mm. Patients with recessions greater than 3 mm underwent no changes.

DEPTH OF PROBING

The depth of probing variable for patients not receiving HRT was considered to be a statistically significant aggravation (p=0.004). In patients who on the first examination had periodontal probing measurements of less than 3 mm, 100% (7 women) showed an increase in the depth of the probing greater than 3-5 mm. Likewise, 38 patients who initially had probing depths greater than 3-5 mm evolved to worse stages, with a periodontal probing depth greater than 5-6 mm (60.52%) and in some cases even greater than 6 mm (7.89%).

In the case of the women treated with dermal patches, the results were statistically significant (p=0.001) since the number of patients who showed an improvement was twice the number of those who got worse. In the 16 patients with probing depths no greater than 3 mm, 25 % of the cases (4 patients) evolved to a periodontal probing depth greater than 3-5 mm. In the cases in which the initial probing depth was greater than 3-5 mm, 4 patients (7.02%) evolved to the category of probing depth greater than 5-6 mm, while the same number of patients (7.02%) evolved to a probing depth of less than 3 mm. When the initial probing depth was greater than 5-6 mm it was observed that 51.28% of the cases (20 patients) in this category before the treatment -that is, on the first visit- evolved to smaller periodontal probing depths while 10.25% of the cases (4 patients) evolved to poorer stages of the condition, with probing depths greater than 6 mm. The 22 patients who initially had periodontal probing depths greater than 6 mm did not show any variations in the second examination.

DISCUSSION

In a study by Allen I.E. (14) carried out on 13,735 postmenopausal women to examine the effects of HRT on osteoporosis and periodontal disturbances, it was reported that HRT was associated with a reduction in periodontal disturbances that women present in the menopause due to estrogen deprivation.

More recent studies (15) have reported that women undergoing HRT have better tooth retention and thus less tooth loss, but further studies would be needed to confirm this. The aim of our study was oriented in this sense and it may provide answers to this issue. Extensive clinical evidence supports the notion that patients receiving HRT administered in dermal patches undergo an improvement in tooth mobility, especially those affected by grades I and II of tooth mobility, thus delaying tooth loss.

Overall, the evidence confirms the association of periodontal disease with bone mineral density, since menopausal women with low bone mineral density not receiving HRT showed greater gingival recession. Regarding this, the results obtained in our study for both women not receiving HRT as well as for those receiving treatment with dermal patches were not statistically significant, although in the latter group it was found (although the results were not statistically significant), that the proportion of women in which the degree of recession decreased was greater than the number of women in which it increased.

Dental pain of periodontal origin is caused by stimulation of the periodontal ligament (17) and most authors (18-21) support the conclusion that pain is associated with the periodontal disturbance. In the present study no statistically significant differences between patients not undergoing HRT and those who did were found, pain remaining a constant in both groups.

In relation to depth of the periodontal probing, some authors (22) failed to find any statistically significant differences (p= 0,625) between the probing of healthy teeth and the probing of teeth with gingival inflammation. The results obtained here were considered significant (p=0.001), indicating an improvement in the depth of the probing in patients receiving HRT.

Although the existence of estrogen receptors in the gingiva and periodontal ligament was not analyzed in our study, it was considered that this may play an important role in maintaining or improving the different variables analyzed in the women undergoing HRT, as proposed by many authors (23-28).

Hormone replacement therapy with estrogens improves periodontal symptoms in postmenopausal women (23). It has been reported (24) that most patients responding to HRT have estrogen receptors in the epithelium of the oral mucosa. This implies that the identification of estrogen receptors in the oral mucosa could help to select patients that could benefit from this therapy.

Vittek (26) described the existence of these receptors in the gingiva and periodontal ligament, thus confirming that the cytoplasm of gingival cells contains a receptor that binds specifically to 17-beta-estradiol and to moxestrol. These receptors are found in the basal layer of the gingival epithelium, in fibroblasts and in the lamina propria of the endothelium of small vessels. Such results supply the first evidence that gingival tissue can be considered as a target organ for estrogens. Other authors (27) have made use of cultured periodontal ligament cells to examine the binding capacity of steroid hormone (17-beta-estradiol), demonstrating that periodontal ligament cells contain high-affinity receptors for several steroid hormones, suggesting that these cells could be target organs of estrogens. Similarly, specific steroid receptors have been found in the gingiva.

According to the latest studies (29), which include the HERS and HERS II (Heart and Estrogen/Progestin Replacement Study) trials and the WHI study, it must be considered that there is an increased risk of cardiac coronary disease and for breast cancer associated with HRT. Taking this into account, the FDA (Food and Drug Administration) has recommended low-dose of conjugated-estrogens therapy during the shortest period possible.

CONCLUSIONS

HRT acts as a protecting factor against tooth mobility and improves the depth of periodontal probing. Regarding gingival recession and the dental pain, no significant results were obtained either for patients not receiving HRT or for patients being treated with dermal patches.

The above gingival-periodontal clinical evaluation is important for the general stomatologist since it allows easy diagnosis of an already existing periodontal disease in menopausal women due to bone mass loss.

The response to HRT in periodontal disease is probably favored by the existence of estrogen receptors localized in the gingiva and periodontal ligament.

REFERENCES

1. Orozco P. Actualización en el abordaje y tratamiento de la osteoporosis 2001. Información terapéutica del SNS 2001;25:117- 41.        [ Links ]

2. Bungay GT, Vessey MP, Mc Pherson CK. Study of symptoms in middlelife with special reference to the menopause. Br Med J 1980;2:181-3.        [ Links ]

3. Palacios S, Menéndez C, Cifuentes L. Cumplimiento de la terapia hormonal sustitutiva. Cuadernos de Medicina Reproductiva 1999;4:339-54        [ Links ]

4. Ederveen AG, Kloosterboer HJ. Tibolone, a steroid with a tissue-specific hormonal profile, completely prevents ovariectomy-induced bone loss in sexually mature rats. J Bone Miner Res 1999;14:1963-70.        [ Links ]

5. Varney LF, Parker RA, Vincelette A, Greenspan SL. Classification of osteoporosis and osteopenia in postmenopausal women is dependent on site specific analysis. J Clin Densitometry 1999;2:275-83.        [ Links ]

6. Blake GM, Glüer CC, Fogelman I. Bone densitometry: current status and future prospects. Brit J Radiol 1997;70:177-86.        [ Links ]

7. Payne JB, Reinhardt RA, Nummikoski PV, Patil KD. Longitudinal alveolar bone loss in postmenopausal osteoporotic/osteopenic women. Osteoporos Int 1999;10:34-40.        [ Links ]

8. Payne JB, Zachs NR, Reinhardt RA, Nummikoski PV, Patil K. The association between estrogen status and alveolar bone density changes in postmenopausal women with a history of periodontitis. J Periodontol. 1997;68:24-31.        [ Links ]

9. Nyman S, Lindhe J. Exploración de pacientes con enfermedad periodontal. En Lindhe J, Karring T, Lang N, Eds. Periodontología clínica e implantología odontológica. Madrid: Médica Panamericana Editores; 2000. p. 387-99.        [ Links ]

10. Neter J, Cutner H, Nachtsheim CH J, Wasserman W, Eds. Applied Linear Statistical Models. United States: IRWIN Editores; 1996. p. 6-82        [ Links ]

11. McNemar Q. Note on the sampling error of the difference between correlated proportions or percentages. Psychometrika 1947;12:153-157.        [ Links ]

12. Armitage P, Berry G, Eds. Statistical Methods in Medical Research. Oxford: Blackwell Scientific Editores; 1994. p. 98-214.        [ Links ]

13. Fleiss JL, Eds. Statistical Methods for Rates and Proportions. N. J. : Wiley Editores; 1981. p. 18-123.        [ Links ]

14. Allen IE, Monroe M, Connelly J, Cintron R, Ross SD. Effect of postmenopausal hormone replacement therapy on dental outcomes: systematic review of the literature and pharmacoeconomic analysis. Manag Care Interface 2000; 13:93-9        [ Links ]

15. Mattson JS, Cerutis DR, Parrish LC. Osteoporosis: a review and its dental implications. Compend Contin Educ Dent 2002;23:1001-14        [ Links ]

16.Ronderos M, Jacobs DR, Himes JH, Pihlstrom BL.Associations of periodontal disease with femoral bone mineral density and estrogen replacement therapy: cross-sectional evaluation of US adults from NHANES III. J Clin Periodontol 2000;27:778-86.        [ Links ]

17. Mason AG, Scott BJ, van der Glas HW, Linden RW, Cadden SW. Remote noxious stimuli modulate jaw reflexes evoked by activation of periodontal ligament mechanoreceptors in man. Exp Physiol 2002;87:699-706.        [ Links ]

18.Glick DH. The interpretation of pain of dental origin. Dent Clin North Am 1967;11:535-48.        [ Links ]

19.Hall EH, Terezhalmy GT, Pelleu GB Jr. A set of descriptors for the diagnosis of dental pain syndromes. Oral Surg Oral Med Oral Pathol 1986;61:153-7.        [ Links ]

20. Ellegaard B. Periodontal pain . Tandlaegebladet. 1987;91:222-4.        [ Links ]

21.Annino DJ Jr, Goguen LA. Pain from the oral cavity. Otolaryngol Clin North Am 2003;36:1127-35.        [ Links ]

22. Molina GO, Souza SL, Grisi MF, Novaes AB Jr, Taba M Jr. The influence of gingival health status on periodontal probing measurements. A clinical study in humans. J Int Acad Periodontol 2004;6:56-62.        [ Links ]

23. Genco RJ, Grossi SG. Is estrogen deficiency a risk factor for periodontal disease? Compend Contin Educ Dent Suppl 1998;22:23-9        [ Links ]

24. Yin D, Gao W, Kearbey JD, Xu H, Chung K, He Y, et al. Pharmacodynamics of selective androgen receptor modulators. J Pharmacol Exp Ther 2003; 304:1334-40        [ Links ]

25. Forabosco A, Criscuolo M, Coukos G. Efficacy of hormone replacement therapy in postmenopausal women with oral discomfort. Oral Surg Oral Med Oral Pathol 1992;73:570-4.        [ Links ]

26. Vittek J, Hernandez MR, Wenk EJ, Rappaport SC, Southren AL. Specific estrogen receptors in human gingiva. J Clin Endocrinol Metab 1982;54:608-12.        [ Links ]

27. Lewko WM, Anderson A. Estrogen receptors and growth response in cultured human periodontal ligament cells. Life Sci 1986;39:1201-6.        [ Links ]

28. Staffolani N, Guerra M, Pugliese M, Cardinale G, Gulino A. Hormonal receptors in gingival inflammation. Minerva Stomatol 1989;38:823-6.        [ Links ]

29. Deady J. Clinical monograph: hormone replacement therapy. J Manag Care Pharm 2004;10:33-47.        [ Links ]