Effect of levonorgestrel implants on the periodontium

Fibroblasts are the cells chiefly responsible for the repair and overgrowth of gingival tissue. Kavahara and Shimazu [1] have shown that gingival fibroblasts expressed progesterone receptors at low levels in both sexes and all age groups, and that these proteins are not necessarily localized in the nuclei. Working with human fibroblasts cultured in the presence or absence of progesterone, Lapp et al. [2] have shown that the production of the inflammatory mediator interleukin 6 (IL-6) was reduced by 6% to 50% when progesterone was present. Tilakaratne and Soory [3] have alerted to the potentially anabolic and catabolic roles, respectively, of estradiol and progesterone. And Yokoyama et al. [4] have demonstrated that the production of IL-6 and IL-8, the main mediators in periodontal disease, is significantly enhanced by high concentrations of female sex hormones, comparable to those found in the plasma of pregnant women. These findings may point to the modulatory mechanisms involved in both the development of periodontal disease during altered hormonal states and healing responses in the diseased periodontium.

In its active form, progesterone can stimulate the synthesis of prostaglandins, thereby contributing to increased vascular permeability within the chronically inflamed periodontium. To clarify the effect of levonorgestrel implants (Norplant; Wyeth-Ayerst Pharmaceuticals, Philadelphia, PA, USA) on periodontal health, we recruited women for a 6-month follow-up after they received the implants.

The 47 study subjects were randomly selected from a pool of women referred to the Committee for Family Planning Research to receive levonorgestrel implants, and they were then matched for age with 148 healthy women who used barrier methods of contraception (approximately 3 controls matched per study participant).

At the first visit, each participant received a gingival examination that included the following: measurement of gingival pocket depth (mm); determination of the gingival index (assessment of morphologic features such as color and thickness of the gums, and assessment of bleeding when the gums are probed) and determination of the papillary bleeding index (assessment of bleeding when the gingival pockets are probed), as measures of the inflammatory activity; and determination of the plaque index as a measure of the oral hygienic condition. A blood sample was obtained to measure the level of progesterone.

The effect of the levonorgestrel implant on the periodontium was studied after 6 months of use. The gingival, papillary bleeding, and plaque indices were calculated again. All teeth were included in this examination except the wisdom teeth, and they were grouped as molars, premolars, and anterior teeth (incisors and canines). The serum level of progesterone was measured using a standard enzyme-linked immunosorbent assay kit (kit DB52181; IBL, Hamburg, Germany).

The Mann-Whitney test was used for comparisons of independent variables within the groups and the test was used for comparisons between the case and control groups at 6 months. A 2-tailed P value less than 0.05 was considered statistically significant.

The gingival index was significantly increased for the molar and premolar teeth at 6 months (P=0.03 and P=0.04, respectively). No differences were found for the plaque or the papillary bleeding indices in distal, mesial, or middle aspects of the teeth.

In the study group, the pocket depth around the distal (P=0.001) and middle (P=0.001) aspects of the anterior teeth and the middle aspect of the premolars (P=0.02) was significantly increased at 6 months (Table 1). In comparison with the control group, except around the distal aspect of the premolars (P=0.09) and the mesial aspect of the anterior teeth (P=0.07), pocket depth was significantly increased in the study group (Table 1).

Table 1. Depth of the gingival pocket around the different teeth at baseline and at 6 months in women using levonestrogel implantsa

	Aspect of teeth by group	At baseline (mm)	At 6 mo. (mm)	P valueb	Controls (mm)	P valuec
	Molars
	Distal	3.77±0.66	3.96±0.69	0.051	2.87±0.24	0.049
	Mesial	2.50±0.41	2.54±0.41	0.6	2.17±0.24	0.003
	Middle	3.52±0.57	3.72±0.69	0.07	3.14±0.68	0.032
	Premolars
	Distal	3.22±0.91	3.83±1.13	0.13	3.62±0.25	0.09
	Mesial	2.21±0.25	2.34±0.31	0.06	2.03±0.78	0.002
	Middle	3.28±0.57	3.61±0.55	0.02	2.90±0.10	0.02
	Anterior teeth
	Distal	3.55±0.65	3.69±0.65	0.001	3.00±0.87	0.001
	Mesial	2.25±0.43	2.35±0.36	0.061	2.24±0.45	0.07
	Middle	3.29±0.49	3.58±0.57	0.001	2.52±0.85	0.004

a Values are given as mean ± SD unless otherwise indicated. b Comparison of baseline and 6-month values within the case group using the Mann-Whitney test. c Comparison between the case and control groups at 6 months using the test.

No significant relation was found between progesterone level and any of the indices (P=0.09). The hormone level was significantly higher in the case group than in the control group (P<0.001).

The quantitative findings of this study show an association between contraception with levonorgestrel implants and deeper gingival pockets after 6 months, with almost all the teeth affected by periodontitis.