REVIEW
Australian Dental Journal 2005;50:(3):138-145
Effects of endogenous sex hormones on the periodontium –
Review of literature
GN Güncü,* TF Tözüm,† F Çağlayan‡
Abstract
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. The
authors conducted a Medline search up to 2004 and
in addition, a manual search was also performed
including bibliographies of relevant papers, review
articles and books. This review focuses on the effects
of endogenous sex hormones on the periodontium
and the goal was to inform and update practitioners’
knowledge about the impact of these hormones on
periodontal status. In addition, this review article
will analyze how these hormones influence the
periodontium at different life stages such as puberty,
menstruation, pregnancy, menopause and post-
menopause. Moreover, the effects of contraceptives
and hormone replacement therapies on the
periodontium will be discussed. It is clear that
endogenous sex steroid hormones play significant
roles in modulating the periodontal tissue responses.
A better understanding of the periodontal changes to
varying hormonal levels throughout life can help the
dental practitioner in diagnosis and treatment.
Key words: Steroid hormones, periodontium, periodontal
diseases, female, male.
Abbreviations and acronyms: DHT = dihydrotesterone; ERT
= estrogen replacement therapy; HRT = hormone replacement
therapy; IL-6 = interleukin-6; OPG = osteoprotegerin; PMNL
= polymorphonuclear leukocytes.
(Accepted for publication 7 October 2004.)
INTRODUCTION
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
*PhD Student, Department of Periodontology, Faculty of Dentistry,
Hacettepe University, Ankara, Turkey.
†Assistant Professor, Department of Periodontology, Faculty of
Dentistry, Hacettepe University, Ankara, Turkey.
‡Professor and Head, Department of Periodontology, Faculty of
Dentistry, Hacettepe University, Ankara, Turkey.
138
reproduction, growth and development and the
maintenance of internal environments as well as energy
production, utilization and storage.1 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 Currently accepted periodontal
disease classification recognizes the influence of
endogenously produced sex hormones on the
periodontium. 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 Therefore,
this review will focus on the effects of endogenous sex
hormones on the periodontium to update practitioners’
knowledge about the impact of these hormones on
periodontal status. The authors conducted a Medline
search up to 2004. In addition, a manual search was
also performed including bibliographies of relevant
papers, review articles and books. The articles selected
for further review included those published in English in
peer-reviewed journals.
Androgens (testosterone)
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. 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
Androgens may play a significant role in the
maintenance of bone mass and inhibit osteoclastic
Australian Dental Journal 2005;50:3.
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
Testosterone receptors are found in the periodontal
tissues14 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 Kasasa and Soory17
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. 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.
Similarly Gornstein et al.19 found androgen receptors
on both human gingival and periodontal ligament
fibroblasts, and androgens reduced IL-6 production by
cells with these receptors. It is also clear that
testosterone has inhibitory effects in the
cyclooxygenase pathway of arachidonic acid
metabolism in the gingiva by inhibiting prostaglandin
secretion.20 These results showed that testosterone may
have anti-inflammatory effects on the periodontium.18-20
An effective way to analyze the effect of androgens on
bone metabolism is the evaluation of bone remodelling
biochemical markers. 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 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
These data suggest that OPG may be important as a
paracrine mediator of bone metabolism in elderly men
and highlight the role of estrogens in the homeostasis of
the male skeleton.24
The effects of androgens on the periodontium are
summarized in Table 1.
Estrogen and progesterone
Women change physically through the production of
sex hormones at puberty. This begins with the secretion
Table 1. Effects of androgens on the periodontal
tissues
• Inhibit prostaglandin secretion20
• Enhance osteoblast proliferation and differentiation11,13
• Reduce IL-6 production during inflammation18,19
• Enhance matrix synthesis by periodontal ligament fibroblasts and
osteoblasts16
Australian Dental Journal 2005;50:3.
by the anterior pituitary of gonadotropin hormones
(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. Estradiol is additionally secreted by
the placenta and certain peripheral tissues.26 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
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
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 Estrogen receptors are
also found on periosteal fibroblasts, scattered
fibroblasts of the lamina propria, and also periodontal
ligament fibroblasts and osteoblasts.36,37 The effects of
estrogen and progesterone on the periodontium are
summarized in Tables 2 and 3.
Table 2. Effects of estrogen on the periodontal tissues
• Decreases keratinization while increasing epithelial glycogen that
results in the diminution in the effectiveness of the epitelial
barrier38
• Increases cellular proliferation in blood vessels39,40
• Stimulates PMNL phagocytosis41
• Inhibits PMNL chemotaxis42
• Suppress leukocyte production from the bone marrow43,44
• Inhibits proinflammatory cytokins released by human marrow
cells45
• Reduces T-cell mediated inflammation43
• Stimulates the proliferation of the gingival fibroblasts46
• Stimulates the synthesis and maturation of gingival connective
tissues46
• Increases the amount of gingival inflammation with no increase
of plaque47
Table 3. Effects of progesterone on the periodontal
tissues
• Increases vascular dilatation, thus increases permeability2
• Increases the production of prostaglandins48
• Increases PMNL and prostaglandin E2 in the gingival crevicular
fluid (GCF)48,49
• Reduces glucocorticoid anti-inflammatory effect50
• Inhibits collagen and noncollagen synthesis in PDL fibroblast10,51
• Inhibits proliferation of human gingival fibroblast proliferation9
• Alters rate and pattern of collagen production in gingiva resulting
in reduced repair and maintenance potential33,52
• Increases the metabolic breakdown of folate which is necessary
for tissue maintenance and repair33,52
139
Periodontal manifestations related to endogenous sex
hormones
Puberty
Puberty marks the initiation of changes from
maturation into adulthood.49 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 Increased gingival inflammation was
positively correlated with an increase in serum estradiol
and progesterone, and was not accompanied by a
significant change in the mean plaque index.54
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.56 Especially, there is an
increased prevalence of certain bacterial species such as
Prevotella intermedia and Capnocytophaga species.57
Both estradiol and progesterone have been shown to
selectively accumulate by P.intermedia as a substitute
for vitamin K, and thus postulated to be acting as a
growth factor for this microorganism.58 Capnocytophaga
species have also been noted to increase in number as
well as proportion in the subgingival milieu during
puberty, and have been shown to correlate with an
increased bleeding tendency.57 A brief summary is given
in Table 4, and Fig 1a and 1b demonstrate the severity
of gingival inflammation in children at puberty.
Table 4. Clinical and microbial changes in the
periodontal tissues during puberty
• Increased gingival inflammation without accompanying an
increase in plaque levels1,53,54
• Increased prevalence of certain bacterial species such as P.
intermedia and Capnocytophaga species13,14
Menstruation
The onset of increased production, and secretion of
estrogen and progesterone in a cyclic pattern
accompanies the onset of puberty and is referred to as
the reproductive or menstrual cycle.9 The duration of
normal reproductive cycle is 28 days,9 and the monthly
reproductive cycle has two phases.2,59 The first phase is
the follicular or proliferative phase where the levels of
follicle stimulating hormone and estrogen are elevated,9
and estrogen peaks approximately two days before
ovulation. After ovulation the secretory or luteal phase
begins at approximately day 14 of the cycle. This phase
is characterized by the synthesis and release of estrogen
and progesterone by the follicular cells, which have
become the corpus luteum.9 If fertilization does not
occur, the corpus luteum will degenerate, plasma levels
of estrogen and progesterone will decline, and
menstruation will ensue.9,59
During the menstrual cycle, progesterone peaks at
approximately 10 days (increases from the second
week), and drops prior to menstruation.60 Progesterone
140
a
b
Fig 1a and 1b. Severe gingival inflammation is noted at
interproximal sites at puberty.
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 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
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 progesterone
is observed. 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
During the luteal phase of the cycle, when
progesterone reaches its highest concentration,
intraoral recurrent aphthous ulcers,65 herpes labialis
lesions and candida infections may also occur in
women.66 The clinical effects of menstruation are
summarized at Table 5.
Pregnancy
Some of the most remarkable endocrine related oral
alterations occur during pregnancy due to increased
Table 5. Clinical changes in the periodontal tissues
during menstruation
• Bleeding and swollen gingiva48,62,63
• An increase in gingival exudate55,57
• A minor increase in tooth mobility62
Australian Dental Journal 2005;50:3.
plasma hormone levels.9 Upon fertilization and
implantation, the corpus luteum continues to produce
estrogen and progesterone while the placenta develops.
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
Pregnancy gingivitis is extremely common occurring
in a range between 30 and 100 per cent of all pregnant
women.68,69 Pinard first described this situation in 1877
characterized with erythema, edema, hyperplasia and
increased bleeding.70 Cases range from mild
inflammation to severe hyperplasia, pain and
bleeding.52 Increased gingival probing depths,71-74
increased gingival inflammation,75 increased gingival
crevicular fluid flow,71 increased bleeding upon
probing73 and increased tooth mobility72,74 are the
clinical periodontal manifestations that have been
described during pregnancy. The anterior region of the
mouth is more commonly affected and the
interproximal sites tend to be the most involved areas.72
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 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 Figure 2 demonstrates mild
gingival inflammation at the marginal gingivae during
pregnancy.
There is also an increased incidence of pyogenic
granulomas during pregnancy at a prevalence of 0.2 to
9.6 per cent.49 The ‘pregnancy tumour’ or ‘pregnancy
associated pyogenic granuloma’ appears most
commonly during the second or the third month of
pregnancy.9 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. The tumour may be
Fig 2. Mild gingival inflammation is demonstrated at marginal
gingivae.
Australian Dental Journal 2005;50:3.
sessile or pedunculated and may range from purplish
red to deep blue in colour with small fibrin spots.25
Increased sex steroid hormones have effects on
gingival vasculature, subgingival microbiata, specific
cells of periodontium and local immune system during
pregnancy.9 Increased edema, erythema, gingival
crevicular exudate and hemorrhagic gingival tissues
may also be observed due to the effects of estrogen and
progesterone on the gingival vasculature.49,71
Kornman and Löesche77 reported that increased
levels of estrogen and progesterone paralleled gingival
conditions and the proportions of P.intermedia during
pregnancy. 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 Clinical and microbial changes in
the periodontal tissues during pregnancy are
summarized in Table 6.
Table 6. Clinical and microbial changes in the
periodontal tissues during pregnancy
• Increased gingival probing depths71-74
• Increased gingival inflammation75
• Increased gingival crevicular fluid flow71
• Increased bleeding upon probing73
• Increased tooth mobility72,74
• Increased incidences of pyogenic granulomas48
• Increased numbers of periodontopathogens especially P. gingivalis
and P. intermedia68,77
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 This down-regulation can affect
the development of localized inflammation, and gingiva
becomes less efficient at resisting the inflammatory
challenges produced by bacteria.79
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).
However, the initial formulations contained higher
concentrations of sex hormones (20-50μg estrogen and
0.15-4mg progesterone).80
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 This suggests a relationship between
141

Fig 3. Increased inflammation and hemorrhagic gingival sites are
observed at maxillary area.
the use of oral contraceptives and the occurrence of
gingival melanosis.81,82
A 50 per cent increase in gingival fluid volume has
been reported in women using oral contraceptives for a
period of 12 months compared to those who were not
on birth control pills.83 Kalkwarf84 reported that the
response might be due to alterations of
microvasculature, increased gingival permeability and
the increasing synthesis of prostaglandins.
As well as these signs, there are no significant
differences in plaque index and gingival index scores
and attachment level between the oral contraceptive
group and the controls.85 However, a 16-fold-increase
in Bacteroides species has been noted in the oral
contraceptive user group versus a non-pregnant group
despite the lack of statistically significant clinical
differences in gingival index or crevicular fluid.68
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
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
Impacts of contraceptives on clinical and microbial
features of periodontal tissues are summarized in
Table 7.
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
Table 7. Impact of contraceptives on clinical and
microbial features of periodontal tissues
• Inflammation ranges from mild edema and erythema to severe
inflammation with hemorrhagic or hyperplastic gingival tissues60
• A 50 per cent increase in gingival fluid volume83
• A 16-fold-increase in Bacteroides species59
142
Katz and Epstein88 suggested that peripheral conversion
of androgens to estrogens might be the main factor for
protecting bone since estrogens have inhibitory effects
on osteoclastic functions. 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
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
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 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 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 The
results demonstrated that the height of the edentulous
ridge correlated with total body calcium and
mandibular mass.95 It was also reported that skeletal
bone mineral density is related to interproximal
alveolar bone loss and, to a lesser extent, to clinical
attachment loss.94 All of these studies speculated
osteopenia is a risk factor for periodontal disease in
postmenopausal women.
The effects of reduced estrogen levels on epithelial
keratinization96 along with decreased salivary gland
flow,97 may have other significant effects on the
periodontium. Women may demonstrate menopausal
gingivostomatitis94 and the clinical signs of this disease
are drying of the oral tissues, abnormal paleness of the
gingival tissues, redness and bleeding on probing and
brushing (Table 8).98 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 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
Symptoms of the climacteric and postmenopausal
Table 8. Clinical changes in the periodontal tissues
during menopause and postmenopause
• Reduction in epithelial keratinization96
• A reduction in salivary gland flow97
• Drying of the oral tissues98
• Redness and abnormal paleness of the gingival tissues98
• Bleeding on probing and brushing98
Australian Dental Journal 2005;50:3.
period have been shown to disappear with
administration of exogenous estrogens, either alone or
in combination with progestogens.89 Paganini-Hill101
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. 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 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 These data
suggested that postmenopausal HRT protected against
tooth loss and reduced the risk of edentulousim.105
Effects of HRT on the periodontal tissues are
summarized in Table 9.
Table 9. Effects of HRT on the periodontal tissues
• A protection takes place against tooth loss102
• Reduction in gingival bleeding103
• Reduction in the risk of edentulousim104
CONCLUSION
It is clear that endogenous sex steroid hormones play
significant roles in modulating the periodontal tissue
responses and may alter periodontal tissue responses to
microbial plaque, and thus directly may contribute to
periodontal disease. They can influence the
periodontium at different life times such as puberty,
menstruation, pregnancy, menopause and
postmenopause. A better understanding of the
periodontal changes to varying hormonal levels
throughout life can help the dental practitioner in the
diagnosis and treatment. The influence of sex
hormones on periodontal wound healing is still largely
unclear. Further research is needed to improve the
understanding of how endogenous sex steroid
hormones influence the periodontal wound healing.
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Address for correspondence/reprints:
Dr Tolga F Tözüm
Department of Periodontology
Faculty of Dentistry
Hacettepe University
Sihhiye TR-06100 Ankara
Turkey
Email: ttozum@hacettepe.edu.tr
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