This document discusses the effects of endogenous sex hormones on the periodontium. It begins by explaining that hormones play an important role in homeostasis of the periodontium and can influence periodontal conditions. It then examines the specific effects of androgens, estrogens, progesterone, and how these hormones may impact the periodontium during puberty and the menstrual cycle. The document concludes by stating that periodontal manifestations can occur when there is an imbalance in these sex hormones.
4. THE NORMAL
PERIODONTIUM
• - The periodontium is composed of a group of
tissues that support and protect the teeth: gingiva
cementum, periodontal ligament, and alveolar
bone.
• The alveolar bone proper, the cementum, and the
periodontal ligament form the attachment apparatus
of the tooth.
5. • -From the oral surface point of view, the
periodontium consists of:
• 1-Attached and marginal gingiva.
• 2- A free gingival groove that separates the
attached gingiva from the marginal gingiva.
• 3- Lining (alveolar) mucosa .
• 4-Mucogingival junction that separates the
attached gingiva from the alveolar mucosa.
6. Macro-anatomy of the gingiva
Free gingiva
Free
gingival
groove
Interdental
papilla
Attached
gingiva
Mucogingival
junction
Alveolar
mucosa
12. CEMENTUM CAN ALSO BE
CLASSIFIED INTO:
I. Based on cellular component
1. Cementum containing cells
a.) Cellular cementum
b.) Intermediate cementum
2. Acellular cementum
13. • II. Based on fibrillar component
1. Intrinsic fibers cementum
(Fibers secreted by cementoblasts).
2. Extrinsic fibers cementum
(Sharpey’s fibers).
3. Mixed fibers cementum
(Extrinsic 60% + intrinsic 40%).
4. Afibrillar cementum
(Formed by mesenchymal cells after retraction of
reduced enamel epithelium or by attach. epth.).
16. cells
THE PERIODONTAL LIGAMENT IS
FORMED OF :
Fibers,
Intercellular
substances
Synthetic
Resorptive
Progenitor
Defensive
ground substances
blood vessels,
nerves & lymphatics.Epithelial cells
17. A- THE PRINCIPAL FIBERS OF PERIODONTAL
LIGAMENT ARE FORMED OF COLLAGEN BUNDLES,
WHICH ARE WAVY IN COURSE AND ARE ARRANGED IN
THREE LIGAMENTS .
a) Gingival fibers.
b) Transseptal or interdental ligament.
c) Alveolodental ligament which is subdivided
into the following five groups:
1- Alveolar crest group.
2- Horizontal group.
3- Oblique group.
4-Apical group.
5- Interradicular group.
18.
19. ALVEOLAR
PROCESS
•It is that part of the bone of the Jaw (
Mandible or Maxilla ) That Forms and
Supports the sockets of the teeth.
ALVEOLAR
PROCESS
BASAL BONE
20. • Bone components:
*Cellular components
• Osteogenic cells, which form and
maintain bone.
• Osteoclasts, which resorb bone
• *Matrix components
• It is formed of mineral content and
organic extra-cellular matrix (collagen
fiber and ground substance).
24. EFFECTS OF ENDOGENOUS SEX
HORMONES ON THE PERIODONTIUM
• Hormones are specific regulatory molecules that
have potent effects on the major determinants of the
development and the integrity of the skeleton and
oral cavity including periodontal tissues.
• It is clear that periodontal manifestations occur when an
imbalance of these steroid hormones take place.
Australian Dental Journal 2005;50:3.
25. • The homeostasis of the periodontium involves complex
multifactorial relationships, in which the endocrine system
plays an important role. (1)
• Hormones are specific regulatory molecules that
modulate reproduction, growth and development and the
maintenance of internal environments as well as energy
production, utilization and storage.1
Australian Dental Journal 2005;50:3.
26. • Hormones can be classified into four groups based upon
their chemical structure including steroids, glycoproteins,
polypeptides and amines. 2
• As well as being the regulators of reproductive functions, sex
steroid hormones have potent effects on the nervous and
cardiovascular system, and on major determinants of the
development and integrity of the skeleton and oral cavity
including periodontal tissues. 3-5
Australian Dental Journal 2005;50:3.
27. • Under the broad category of dental plaque induced
gingival diseases that are modified by systemic
factors, those associated with the endocrine system are
classified as puberty, menstrual cycle and pregnancy
associated gingivitis. 6
• Researchers have shown that changes in periodontal
conditions may be associated with variations in sex
hormones. 7-9
Australian Dental Journal 2005;50:3
28. • Androgens are concerned with normal spermatogenesis and
are responsible for the development of the secondary sexual
characteristics in male puberty.10
• There are two types of androgens: gonadal androgen,
dihydrotesterone (DHT), and adrenal androgen,
dehydroepiandrosterone.
Australian Dental Journal 2005;50:3
29. • The former is the most active form. The adrenal
androgen, androstenedione, is converted to testosterone
and to estrogens in the circulation, and represents an
important source of estrogens in men and
postmenopausal women. 2
Australian Dental Journal 2005;50:3
30. • Androgens may play a significant role in the
maintenance of bone mass and inhibit osteoclastic
function, inhibit prostaglandin synthesis and reduce
interleukin-6 (IL-6) production during inflammation.11-12
• Further, testosterone stimulates bone cell proliferation
and differentiation and therefore has a positive effect on
bone metabolism.13
• Australian Dental Journal 2005;50:3
31. • Testosterone receptors are found in the periodontal
Tissues (14) and the number of receptors on fibroblasts
tends to increase in inflamed or overgrown gingivae,15
where testosterone has an effect on periodontal tissues by
increasing matrix synthesis. 10,15,16
• Australian Dental Journal 2005;50:3
32. • Kasasa and Soory (17) reported that in response to IL-1,
chronically inflamed human gingival tissues and periodontal
ligament tissues showed an increase in androgen metabolic
activity and insulin like growth factor stimulated DHT
synthesis in gingiva and cultured fibroblasts.
• Australian Dental Journal 2005;50:3
33. • Parkar et al.18 demonstrated that increasing DHT
concentrations progressively reduced IL-6 production by
gingival cells isolated from normal individuals and patients
with gingival inflammation and gingival hyperplasia.
• These results showed that testosterone may have anti-
inflammatory effects on the periodontium.18-20 Australian
Dental Journal 2005;50:3
34. • Osteoprotegerin (OPG) is one of such bone-remodelling
markers. 21,22 OPG, a secreted member of the tumour
necrosis factor receptor superfamily, has been implicated in
the pathogenesis of postmenopausal osteoporosis and other
metabolic bone diseases.23
• Australian Dental Journal 2005;50:3
35. • OPG inhibits osteoclast formation and activation by
neutralizing its cognate ligand.21,22
• During periodontal disease progression, OPG action is
associated with a reduction in the loss of bone mineral
density,21 and serum concentrations of OPG increase
significantly with age, and are positively correlated with free
testosterone index and free estradiol index.24 Australian
Dental Journal 2005;50:3
•
36.
37. ESTROGEN AND
PROGESTERONE
• Women change physically through the production of sex
hormones at puberty. This begins with the secretion by the
anterior pituitary of gonadotropin hormones
• Australian Dental Journal 2005;50:3
38.
39. • (follicle-stimulating hormone and luteinizing hormone), which
causes the ovaries to begin cyclical production and secretion
of female sex hormones (estrogen and progesterone). 25
• Estradiol is the principal premenopausal estrogen and is
produced by the female gonad, the ovary. It is additionally
secreted by the placenta and certain peripheral tissues. 26
• Australian Dental Journal 2005;50:3
40. • Estrogens play a crucial role in many vital activities,
including the development and maintenance of secondary
sex characteristics, uterine growth, pulsatile release of
luteinizing hormone from the anterior pituitary gland and
the development of peripheral and axial skeleton.1,5,27-30
Australian Dental Journal 2005;50:3
41. • Another hormone critical for females is progesterone
secreted by the corpus luteum, placenta, and the adrenal
cortex, and it is active in bone metabolism and has
significant effect in the coupling of bone resorption and
bone formation by engaging osteoblast receptors directly.
1,31
• Australian Dental Journal 2005;50:3
42. • Estrogen and progesterone have significant biological
actions that can effect other organ systems including the oral
cavity.10,32-33
• Receptors for estrogen and progesterone have been
demonstrated in the gingiva, in which the gingiva can be
thought of as a target organ for progesterone and
estrogen.34,35
•
43. Estrogen receptors are also found on periosteal fibroblasts, scattered
fibroblasts of the lamina propria, and also periodontal ligament fibroblasts
and osteoblasts.36,37
46. PUBERTY
• It is associated with a major increase in the secretions of
the sex steroid hormones: testosterone in males and
estradiol in females.2
• Several cross-sectional and longitudinal studies have
demonstrated an increase in gingival inflammation without
accompanying an increase in plaque levels during
puberty.1,53-55 Australian Dental Journal 2005;50:3
49. During the menstrual cycle, During the menstrual cycle, progesterone peaks at approximately 10
days (increases from the second week), and drops prior to menstruation.60at
approximately 10 days (increases from the second week), and drops prior to menstruation.60
MENSTRUATION
50. MENSTRUATION
• Progesterone has been associated with increased
permeability of the microvasculature, altering the rate and
the pattern of collagen production in the gingiva,60
increases folate metabolism,33,52 stimulates the
production of prostaglandins and enhances the
chemotaxis of polymorphonuclear leukocytes (PMNL).61
Australian Dental Journal 2005;50:3
•
51. MENSTRUATION
• As a result, significant gingival inflammatory
changes have been documented in association with
the menstrual cycle, and gingival inflammation
seems to be aggravated by an imbalance and/or
increase in sex hormones.62-64 Australian Dental
Journal 2005;50:3
52.
53. • Bleeding and a swollen gingivae,49,62,63 an increase
in gingival exudate55,57 and a minor increase in tooth
mobility have all been demonstrated during menses.62
• A gradual increase in gingival fluid occurs during the
proliferation phase just before menstruation,63 where an
increase in the production of estrogen and progesteroneis
observed.
Australian Dental Journal 2005;50:3
54. • A peak level of exudate is detected just before
ovulation, coinciding with the highest levels of these
hormones.63 Nevertheless, most women with a
clinically healthy periodontium experience few
significant changes as a result of menstruation.25
Australian Dental Journal 2005;50:3
55. • During the luteal phase of the cycle, when progesterone
reaches its highest concentration,intra oral recurrent aphthous
ulcers,65 herpes labialis lesions and candida infections may
also occur in women.66
56. PREGNANCY
• Some of the most remarkable endocrine related oral
alterations occur during pregnancy due to increased
plasma hormone levels.9Upon fertilization and
implantation, the corpus luteum continues to produce
estrogen and progesterone while the placenta
develops. Australian Dental Journal 2005;50:3
57. • Progesterone and estrogen reach their peak plasma
levels of 100ng/ml and 6ng/ml respectively, by the
end of the third trimester, and the potential biological
impact of estrogen and progesterone take place in
periodontal tissues during this period.1,25,67
Australian Dental Journal 2005;50:3
58.
59. • Gingival inflammatory changes in pregnancy
usually begin during the second month and the
severity of the disease increases through the
eight month, after which there is an abrupt
decrease related to a concomitant reduction in
sex steroid hormone secretion.69
• Australian Dental Journal 2005;50:3
60. • Moreover, it has been confirmed that during pregnancy
the severity of gingival inflammation is correlated to
elevations of sex steroid hormones and is reduced
following parturition and the concomitant drop-off in
hormone production.71
• The ‘pregnancy tumour’ or ‘pregnancy associated
pyogenic granuloma’ appears most commonly during the
second or the third month of pregnancy.9
61. • Gingiva is the most common site involved (70 per cent)
followed by tongue, lips, buccal mucosa and the
palate.76 The pregnancy tumour develops as a result of
an exaggerated inflammatory response to local
irritations, then enlarges rapidly and bleeds easily, and
becomes hyperplastic and nodular.
Australian Dental Journal 2005;50:3
62. • The tumour may be sessile or pedunculated and may
range from purplish red to deep blue in colour with small
fibrin spots.25
• Kornman and Löesche 77 reported that increased
levels of estrogen and progesterone paralleled gingival
conditions and the proportions of P.intermedia during
pregnancy.
Australian Dental Journal 2005;50:3
63. • During the second trimester, an increase in gingivitis and
gingival bleeding without an increase in plaque levels
have been reported and further a 55-fold of an increase
in the proportion of P.intermedia has been reported in
pregnant women compared to non pregnant controls.68
• Australian Dental Journal 2005;50:3
64. • Sex steroid hormones have been shown to have effects
on cellular growth, proliferation and differentiation in
target tissues including keratinocytes and fibroblasts in
the gingiva.1
• Sex steroid hormones may also modulate production of
cytokines,71 and progesterone has been shown to down
regulate IL-6 production by human gingival
fibroblasts.79 Australian Dental Journal 2005;50:3
65. • This down-regulation can affect the development of localized
inflammation, and gingiva becomes less efficient at resisting
the inflammatory challenges produced by bacteria.79
66. CONTRACEPTIVES
• Hormonal contraceptives are agents based on the effects
of gestational hormones that simulate a state of pregnancy
to prevent ovulation.9,49 Oral contraceptive agents are
one of the most commonly used classes of drugs.
• Current oral contraceptives consist of low doses of
estrogens (0.05mg/day) and progestins (1.5mg/day).
Australian Dental Journal 2005;50:3
67. • Gingival tissues may have an exaggerated response to
local irritants. Inflammation ranges from mild edema and
erythema to severe inflammation with hemorrhagic or
hyperplastic gingival tissues60 (Fig 3). It has also been
reported that there may be a spotty melanotic
pigmentation of the skin with the use of oral
contraceptives.81
Australian Dental Journal 2005;50:3
68. • This suggests a relationship between the use of oral
contraceptives and the occurrence of gingival melanosis.
81,82
• Kalkwarf 84 reported that the response might be due to
alterations of microvasculature, increased gingival
permeability and the increasing synthesis of
prostaglandins.
Australian Dental Journal 2005;50:3
69.
70. • Women taking oral contraceptives experience a two fold
increase in the incidence of localized osteitis following
extraction of mandibular third molars due to the effects of
oral contraceptives on clotting factors.86
• Australian Dental Journal 2005;50:3
71. • The estrogen in the oral contraceptives causes a variation
in the coagulation and fibrinolytic factors in women taking
them leading to a greater incidence of clot lysis. 49
Australian Dental Journal 2005;50:3
72. MENOPAUSE AND
POSTMENOPAUSE
• Menopause usually begins between 45 and 55 years of
age unless accelerated by hysterectomy and/or
ovariectomy.2,49
• The levels of estrogen begin to drop mainly during the late
follicular and luteal phase of the menstrual cycle when
women approach menopause.87
• Australian Dental Journal 2005;50:3
73. • Katz and Epstein 88 suggested that peripheral conversion
of androgens to estrogens might be the main factor for
protecting bone since estrogens have inhibitory effects on
osteoclastic functions.
• Australian Dental Journal 2005;50:3
74. • The postmenopausal period is associated with an
increased risk of osteoporotic fractures, myocardial
infarction, menstrual cycle disorders, hot flushes, night
sweats, vaginal dryness and possibly with an early onset of
Alzheimer’s disease.89-91
• Australian Dental Journal 2005;50:3
75. • The most significant problem that develops during
menopause is osteoporosis.49 Osteoporosis is a
worldwide disease characterized by low bone mass and
fragility and a consequent increase in fracture risk.92
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•
76. • Osteoporosis is also responsible for less crestal alveolar
bone per unit volume, a condition that may promote
quicker bone loss when encountered with infections such
as periodontal infections.92
• Australian Dental Journal 2005;50:3
77. • Moreover, osteoporotic/osteopenic women exhibited a
higher frequency of alveolar bone height loss as well as
crestal and subcrestal density loss compared to women
with normal bone density.93
• Australian Dental Journal 2005;50:3
78. • The incidence of periodontitis also correlates with signs of
generalized osteoporosis. 94
• Eighty-five osteoporotic women demonstrated a significant
correlation between skeletal bone mass and the number of
teeth remaining in the mandibular.95
• Australian Dental Journal 2005;50:3
79. • Oral discomfort is also commonly reported by
postmenopausal women with burning sensation,
xerostomia and bad taste.9
• Despite the linkage between menopause and
periodontal disease, menopause may affect the
severity of the present disease.25
Australian Dental Journal 2005;50:3
80. • However, for women with periodontal health, menopause is
not a risk factor.25
• Peri or postmenopausal women take hormone
replacement therapy (HRT) for relieving climacteric
symptoms and increasing the quality of life. 99,100
Australian Dental Journal 2005;50:3
81.
82. • Paganini-Hill (101) analyzed the effects of estrogen
replacement therapy (ERT) on the prevention of tooth loss,
and the proportion of edentulous women was reported to
decrease with increasing duration of ERT.
• Australian Dental Journal 2005;50:3
83. • A two-year follow-up study with 42 171 postmenopausal
women showed that the risk of tooth loss was significantly
lower amongst postmenopausal hormone users, and the anti-
inflammatory effects of estrogen (decreased synthesis of
prostaglandins) could protect against tooth loss. 102 Australian
Dental Journal 2005;50:3
84. • Further, 228 women (50 to 64 years old) taking estrogen
hormonal supplementation had significantly lower gingival
bleeding sites than age-matched controls. 103
• It was also reported that the odds of being edentulous
were reduced by six per cent for each one year increase in
duration of HRT use.104
• Australian Dental Journal 2005;50:3
