Influences of Steroid Sex Hormones on Periodontium during Women Life Cycle

 

• Throughout the reproductive life cycle of women, fluctuating levels of sex hormones during puberty, menses, pregnancy, and menopause have direct and indirect effects on oral health and they also influence their susceptibility to periodontal disease.

• Subgingival microflora epithelial keratinization decreased salivary flo altered gingival crevicular fluid effects on specific cells of periodontium and local immune system burning sensation halitosis interproximal alveolar bone loss clinical attachment loss

• Maternal periodontitis has been associated with adverse pregnancy outcomes: preterm birth, preeclampsia, gestational diabetes, delivery of a small-for-gestational age infant, and fetal loss. The strength of these associations ranges from a 2–7-fold increase in risk

• The homeostasis of the periodontium involves complex multifactorial relationships, in which the endocrine system plays an important role.

• Fluctuating levels of sex hormones during puberty, menses, pregnancy, and menopause have direct and indirect effects on oral health and they also influence their susceptibility to periodontal disease.

• Steroid sex hormones (androgens, estrogens, and progesterone) show effects on cellular growth, proliferation, and differentiation in target tissues including keratinocytes and fibroblasts in the gingiva.

• Steroid sex hormone

  • Sex Hormones are fat soluble compounds (steroids) that control sexual maturity and reproduction.

  • Produced mainly by endocrine glands.

  • Endocrine glands are testes in males and ovaries in women.

  • Females produce mainly estrogens and progesterone, males produce mainly androgens.

  • Sex Hormones are synthesized by cholesterol and from other compounds secreted by different levels of the body over the span of a persons life

  • Production of Sex Hormones

    • Made by gonads (Ovaries in women, Testes in men).
    • Made by adrenal glands.Made by confrontation by other sex hormones in other tissues.
    • Production increases at puberty and decreases at old age.

  • Physiology

  • Estrogens

    • Estradiol is the most potent estrogen and is secreted by the ovary, testis, placenta, as well as peripheral tissues.
    • Estrone is also secreted by the ovary; however, the principal source in both women and men is through extragonadal conversion of androstenedione in peripheral tissues
    • In premenopausal women, the most abundant physiological estrogen is estradiol, and in men and postmenopausal women, the most abundant estrogen in the plasma is estrone.

  • Progestins

    • The natural progestins, or steroids that have progestational activity, are derived from a 21-carbon saturated steroid hydrocarbon known as pregnane.
    • The principal progestational hormone secreted into the bloodstream is progesterone (pregn-4-ene-3,20-dione), which is synthesized and secreted by the corpus luteum, placenta, and adrenal cortex.
    • The biological activities of progestins are principally observed during the luteal phase of the menstrual cycle and pregnancy.

  • Androgens

    In women, the major plasma androgen is androstenedione (androst-4-ene-3,17-dione), which can be secreted into the bloodstream or converted into either testosterone or estradiol by the ovary.

  • Effect of Estrogen on the periodontal tissues

    • Estrogen has significant biological actions on the oral cavity.
    • Receptors for estrogen have been demonstrated in the gingiva, periosteal fibroblasts, scattered fibroblasts of the lamina propria, and also PDL fibroblasts and osteoblasts.
    1. Decreases keratinization while increasing epithelial glycogen that results in the diminution in the effectiveness of the epithelial barrier.
    2. Increases cellular (erythrocytes, granulocytes, platelets, and mast cells) proliferation in blood vessels.
    3. Stimulates polymorphonuclear leukocyte (PMNL) phagocytosis.
    4. Inhibits PMNL chemotaxis.
    5. Suppresses leukocyte production from the bone marrow.
    6. Inhibits proinflammatory cytokines released by human marrow cells.
    7. Reduces T-cell-mediated inflammation.
    8. Stimulates the proliferation of the gingival fibroblasts.
    9. Stimulates the synthesis and maturation of gingival connective tissues.
    10. Increases the amount of gingival inflammation with no increase of plaque.

  • Effect of progesterone of the periodontal tissues

    Progesterone is secreted by the corpus luteum, placenta, and adrenal cortex and is active in bone metabolism and has significant effect in the coupling of bone resorption and bone formation by engaging osteoblast receptors directly.

    1. Increases vascular dilatation, thus increasing permeability.
    2. Increases the production of prostaglandins.
    3. Increases PMNLs and prostaglandin E2 in the gingival crevicular fluid (GCF).
    4. Reduces glucocorticoid anti-inflammatory effect.
    5. Inhibits collagen and noncollagen synthesis in PDL fibroblast.
    6. Inhibits proliferation of human gingival fibroblast proliferation.
    7. Alters rate and pattern of collagen production in gingiva, resulting in reduced repair and maintenance potential.
    8. Increases the metabolic breakdown of folate which is necessary for tissue maintenance and repair.[

  • Effect of Androgens (Testosterone) on Periodontal Tissues

    Testosterone receptors are found in the periodontal tissues, and the number of receptors on fibroblasts tends to increase in inflamed or overgrown gingiva, where testosterone has an effect on periodontal tissues by increasing matrix synthesis. It has inhibitory effects on the cyclooxygenase pathway of arachidonic acid metabolism in the gingiva by inhibiting prostaglandin secretion.

    1. Inhibits prostaglandin secretion.
    2. Enhances osteoblast proliferation and differentiation.
    3. Reduces interleukin-6 production during inflammation.
    4. Enhances matrix synthesis by periodontal ligament (PDL) fibroblasts and osteoblasts.

  • Influence on Periodontium During Puberty

    • A peak prevalence of gingivitis has been determined at 12 years, 10 months in females and 13 years, 7 months in males, which is consistent with the onset of puberty.
    • There is a higher incidence of black-pigmented Bacteroides and higher populations of other Gram-negative rods in the subgingival microflora compared with healthy sulci in puberty.
    • The alteration in the subgingival microflora includes the presence of Prevotella intermedia, which can substitute estrogen and progesterone for Vitamin K, an essential bacterial growth factor, spirochetes, Capnocytophaga sp., Actinomyces sp., and Eikenella corrodens. Capnocytophaga species have been associated with a tendency toward increased bleeding.

  • The characteristics of puberty-associated gingivitis

    1. Plaque present at gingival margin.
    2. Pronounced inflammatory response of gingiva must be circumpubertal as designated by Tanner Stage 2 or greater (girls, estradiol ≥26 pmol/L; boys, testosterone ≥8.7 nmol/L).
    3. Change in gingival color.
    4. Change in gingival contour with possible modification of gingival size.
    5. Increased gingival exudates.
    6. Bleeding upon provocation.
    7. Absence of attachment loss.
    8. Absence of bone loss.
    9. Reversible following puberty.

  • Influence on Peridontium during Menstruantion

    • During the menstrual cycle, progesterone peaks at approximately 10 days (increases from the 2nd week) and drops before menstruation.
    • Progesterone has been associated with increased permeability of the microvasculature, alters the rate and pattern of collagen production in the gingiva, increases folate metabolism, stimulates the production of prostaglandins, and enhances the chemotaxis of PMNLs.

  • The characteristic of mentsrual cycle-associated gingivitis

    1. Plaque present at gingival margin.
    2. Modest inflammatory response of gingiva before ovulation.
    3. Must be at ovulatory surge when luteinizing hormone levels are >25 mLU/mL and/or estradiol levels are >200 pg/mL.
    4. Increase in gingival exudates by at least 20% during ovulation.
    5. Absence of attachment loss.
    6. Absence of bone loss.
    7. Reversible following ovulation.

  • Other complaints seen during menstruation are

    1. Burning sensation in the oral cavity.
    2. Prolonged hemorrhage following oral surgery.
    3. Swollen salivary glands.
    4. Activation of herpes labialis and oral aphthous ulcer.
    5. Infections with Candida albicans.
    6. Estrogen levels have been implicated in menstrual cycle-associated mood changes which have in turn been linked with increased susceptibility to major depression.

  • Influence on Periodontium during Pregnancy

    During pregnancy, both progesterone and estrogen are elevated due to continuous production of these hormones by the corpus luteum. By the end of the third trimester, progesterone and estrogen reach peak plasma levels of 100 and 6 ng/mL, respectively, which represent 10 and 30 times the levels observed during the menstrual cycle.[9]

    The relationship between pregnancy and periodontal inflammation is known since long. In 1788, Vermeeren discussed “tooth pains” in pregnancy. In 1818, Picarin described gingival hyperplasia in pregnancy. In 1877, Pinard recorded the first case of “pregnancy gingivitis.”[10]

    Susceptibility to infections (e.g., periodontal infection) increases during early gestation due to alterations in the immune system and can be explained by the hormonal changes observed during pregnancy, suppression on T-cell activity, decreased neutrophil chemotaxis and phagocytosis, altered lymphocyte response and depressed antibody production, chronic maternal stress, and even nutritional deficiency associated with increased nutritional demand by both the mother and the fetus.[9]

  • The clinical and microbial changes in the periodontal tissues during pregnancy

    1. Increased gingival probing depths.
    2. Increased gingival inflammation.
    3. Increased GCF flow.
    4. Increased bleeding upon probing.
    5. Increased tooth mobility.
    6. Increased incidence of pyogenic granulomas.
    7. Increased number of periodontopathogens, especially P. gingivalis and P. intermedia.

  • The characteristics of pregnancy-associated gingivitis

    Plaque present at gingival margin

    Pronounced inflammatory response of gingival

    Onset in pregnant women (second and third trimester)

    Change in gingival color

    Change in gingival contour

    Increase in gingival exudates

    Bleeding upon provocation

    Absence of attachment loss

    Absence of bone loss

    Reversible at parturition.

  • The characteristics of pregnancy-associated pyogenic granuloma/pregnancy tumor/granuloma gravidarum/epulis gravidarum are:

    Plaque present at gingival margin

    Pronounced inflammatory response of gingival

    Can occur anytime during pregnancy

    More common in maxilla

    More common interproximally

    Sessile or pedunculated protuberant mass

    Not a neoplasm, has histologic appearance of a

    pyogenic granuloma

    Regresses following parturition.

  • Periodontal infection is one of many infections that have been associated with adverse pregnancy outcomes. Recent research suggests that the presence of maternal periodontitis has been associated with adverse pregnancy outcomes, such as preterm birth, preeclampsia, gestational diabetes, delivery of a small-for-gestational-age infant, and fetal loss. The strength of these associations ranges from a 2–7-fold increase in risk. The increased risks suggest that periodontitis may be an independent risk factor for adverse pregnancy outcomes.[11]

• Influence on Periodontium During Menopause

  In the menopause stage, the estrogen levels decline rapidly and lead to systemic bone loss.

  Estrogen deficiency leads to up-regulation of immune cells (macrophages and monocytes) and osteoclasts, which are responsible for a greater production of bone-resorbing cytokines.

  Lipopolysaccharide-released by-products related to periodontal tissues and bacterial plaque biofilm stimulate the production of inflammatory cytokines, which further activates the osteoclasts that resorb the bone.

• Oral manifestations at menopause

  • Oral discomfort

    • Pain
    • Burning sensation
    • Modification of the gustatory sensations (salty, hot, and sour)
    • Xerostomia

  • Modifications of the oral mucous membrane

    • Gingival atrophy
    • Menopause gingivostomatitis

  • Other symptom

    • Lichen planus
    • Neurological disorders
    • Eating disorders

  • Osteoporosis

    • Severe osteoporosis-rapid loss of teeth and atrophy of the residual edentulous ridge
    • Accelerated bone atrophy
    • May affect the severity of the preexisting periodontopathy.

  • Management

    • Throughout a woman's life cycle, hormonal influences affect therapeutic decision-making in periodontics.
    • Oral health-care professionals have greater awareness of, and better capabilities for dealing with, hormonal influences associated with the reproductive process.
    • Periodontal and oral tissue responses may be altered, creating diagnostic and therapeutic dilemmas. Therefore, it is imperative that the clinician recognize, customize, and appropriately alter periodontal therapy according to the individual woman's needs based on the stage of her life cycle

  • Management during menopause

    • If the patient is susceptible to osteoporosis, the dentist should consult the patient's physician as to the risks versus benefits of hormone replacement therapy (HRT)/estrogen replacement therapy and calcium/Vitamin D supplementation for the individual patient.

    • The National Institutes of Health (1994 Conference on Optimal Calcium Intake) recommends as follows: Premenopausal women (25–50 years old), 1000 mg/day

      Postmenopausal women (estrogen therapy), 1000 mg/day

      Postmenopausal women (no estrogen therapy), 1500 mg/day

      Women >65 years old, 1500 mg/day.

    • Sodium fluoride, bisphosphonates (e.g., alendronate), selective estrogen receptor modulators, and parathyroid hormone may be other therapies for the osteoporotic patient.

  • Effects of Oral Contraceptives on the Periodontium

    The use of hormonal contraceptives by women has been considered to influence gingival and periodontal disease progression. The two possible factors influencing the effects of oral contraceptives (OCPs) on periodontal condition include hormonal dosage and the total duration of intake. A continued exposure of OCPs used for a longer period results in a higher risk to periodontal disease development and progression because of increased production of proinflammatory cytokines and prostaglandins resulting from elevated levels of these hormones.

    Gingival tissues may have an exaggerated response to local irritants. OCPs can aggravate patients' inflammatory condition, causing erythema and an increased propensity to gingival bleeding. Inflammation may vary from mild edema, erythema to severe inflammation with hemorrhagic or hyperplastic gingival tissues. There is evidence that the presence of metabolic products of the sex hormones in gingiva is an essential factor in the pathogenesis of chronic gingivitis

    • Ginggival Hyperplasia

      OCPs have been reported to induce gingival enlargement.

      The incidence of gingival overgrowth by OCPs is common and resolves when the drug is withdrawn.

      Maintenance of adequate plaque control is essential for gingival health during the intake of OCPs

    • Pigmentation of the oral mucosa

      Pigmentation of the oral mucosa can be caused by the use of OCPs, and withdrawal of the drug does not produce complete regression.

      Estrogens are well known to induce high levels of cortisol-binding globulin which leads to a decrease in plasma-free cortisol.

      This produces a hypersecretion of adrenocorticotropic hormone and melanocyte-stimulating hormone, the latter may cause increased pigmentation of the oral mucosa

  • Alveolar osteitis

    OCP is the only medication associated with developing alveolar osteitis following extraction of impacted lower third molars.

    Estrogen plays a significant role in the fibrinolytic process, which is believed to indirectly activate the fibrinolytic system, contributing to the premature destruction of the clot and the development of dry socket.

  • Saliva

    Several changes have been observed in the composition and flow of saliva in women taking contraceptive medications.

    There is a decrease in concentrations of protein, sialic acid, hydrogen ions, and total electrolytes.

    Studies have shown both an increase and a decrease in salivary flow. A study has also shown that salivary buffer effect of OCP users is significantly higher than nonusers.

  • Effect of Phytoestrogens on Osteoporosis

    Phytoestrogens are plant compounds that are structurally and functionally similar to β-estradiol and bind to estradiol receptors. Whereas their affinity for binding is only 1/500–1/1000 of that of estradiol, they compete with estradiol for receptor sites. As a result, phytoestrogens are thought to act as both agonists and antagonists

    Soy isoflavones may be useful in preventing and treating postmenopausal osteoporosis due to their similarity in structure to estradiol. They may thus act as potential replacements for estrogen deficiency