Periodontology 2000, Val.
6, 1994, 79-87
Printed in Denmark. All rights reserued
Influence of hormonal variation
on the periodontium in women
AMAR& KONG MUNCHUNG
SALOMON
Hormones exert significant influence in body physi-
ology throughout life. Women, in particular, experi-
ence hormonal variation under both physiological
and nonphysiological conditions, such as hormonal
therapy or the use of oral contraceptives. This vari-
ation significantly affects women’s health. This chap-
ter focuses on hormonal influences on women’s
bodies reflected in the periodontium as hormonal
variation affects the physiology of host-parasite in-
teractions in the oral cavity.
At puberty, women change physically through the
production of sex hormones (estrogen and pro-
gesterone). This begins with the anterior pituitary
secretion of gonadotropin hormones (follicle-stimu-
lating hormone and luteinizing hormone) that
causes the ovaries to begin cyclical production and
secretion of the female sex hormones (estrogen and
progesterone). Estrogen induces several of the devel-
opmental changes observed in women during pu-
berty, and progesterone acts synergistically with es-
trogen to control the menstrual cycle and inhibits
follitropin secretion by the anterior pituitary. In ad-
dition, progesterone effects both progestational
changes in the endometrium and cyclical changes in
the cervix and vagina. These female sex hormones
also have other significant biological actions that can
affect other organ systems including the oral cavity
(38-40, 48, 50, 61) (Fig. 1). Styrt & Sugarman (63)
found from animal and human studies that preg-
nancy, estrogen supplementation and menstr ual
stage can affect the acquisition and severity of cer-
tain bacterial, parasitic and viral infections, leading
to a possible predisposition to increased infectious
morbidity in certain high-estrogen states. Receptors
for estrogen and progesterone have been demon-
strated in the gingiva, providing evidence that this
tissue can be a target organ for both sex hormones
(67, 68). This chapter reviews and discusses the
unique considerations and factors involving the in-
fluence of sex hormones on the periodontium of
women beginning with puberty, through pregnancy,
Copyright 0 Munksgaard 1994
PERIODONTOLOGY 2000
I S S N 0906-6713
to the peri- and postmenopausal periods of life. Al-
though the factors discussed do not directly cause
periodontal disease they do appear to modify the
periodontium, resulting in decreased resistance to
microbial plaque.
Puberty and menstruation
At puberty, the production of sex hormones in-
creases to a level that remains relatively constant
throughout the normal reproductive period of
women. As a result, pubescent women begin experi-
encing the menstrual cycle (Fig. 2). A number of
studies (12, 13, 43,47, 64) have shown that increased
sex hormone levels correlate with an increased
prevalence of gingivitis followed by remission. How-
ever, the improvement in gingival inflammation is
associated with a reported reduction of dental
plaque and gingival bleeding after the early teens.
Longitudinal and cross-sectional studies on mi-
crobial changes have demonstrated that high bac-
terial counts at the onset of puberty and thereafter
are accompanied by a increased incidence of a num-
ber of bacterial species, some of which are known to
be pathogens (Table 1).
In addition, gingival tissues and the subgingival
microflora respond with a variety of changes as a re-
sult of the increasing hormonal level generated by
the onset of puberty. Mombelli et al. (441, in a longi-
tudinal study, reported that the mean papillary
bleeding and percentage of interdental bleeding
scores correlated with the Tanner index for second-
ary sex characteristics (breast development). How-
ever, other studies (65, 71) were unable to demon-
strate any correlation between the onset of puberty
and gingival condition in parapubescent women.
These differences may be due in part to the baseline
oral hygiene status, the number of teeth or surfaces
measured as well as the design of the study (cross-
sectional versus longitudinal).
79
Amar & Chung

Fig. 1. Influence of estrogen and pro-

gesterone on the periodontal environ-
ment. P: effect of progesterone; E: effect
of estrogen.

Microbial changes have been reported during pu- concentration of hormones present. In particular,
berty and can be attributed to changes in the micro- some gram-negative anaerobes such as Prevotellu in-
environment promoted by the gingival tissue re- termedia have the ability to substitute estrogen and
sponse to the sex hormones as well as the ability of progesterone for menadione (vitamin K) as an essen-
some species of bacteria to capitalize on the higher tial growth factor (31). Furthermore, another gram-
negative bacterium, Cupnocytophaga species, in-
creases in incidence as well as in proportion. This
Follicular Luteal genus has been implicated in the increased bleeding
Phase tendency observed during puberty (19).
Most healthy and periodontally uncompromised

p-
women experience little significant periodontal
consequences as a result of hormonal changes at pu-
berty or during menstruation, since the periodontal
A'-
I .-. ................
, , , , , , / , r: ,,/,, condition improves spontaneously without substan-
tial treatment. However, Holm-Pedersen & Loe (23)
showed that women with gingivitis experienced
exaggerated inflammation reflected by an increased
gingival exudate during menstruation whereas con-
trols with healthy gingiva remain unaffected. Thus,
0

8
4

M
8

4
12

ff
16

f
20
Q
24

F
!
28
-(Days)
OvarianChanges
proper evaluation with prophylactic treatment is
suggested for compromised or susceptible individ-
uals who otherwise require periodontal care.

Fig. 2. The cyclical pattern of hormonal levels effects cor- Pregnancy

responding changes in the ovary and endometrium dur-
ing each menstrual cycle of the reproductive period of
women. FSH: follicle-stimulating hormone; LH: luteiniz- The hormonal changes that occur during pregnancy
ing hormone. include an elevation of both progesterone and estro-

80

Table 1. Subgingival microbial changes during puberty in women
Microbial change
Increased incidence of Cupnocytophuga spp. and
Actinomyces odontolyticus
Increased incidence of spirochetes, Eikenella corrodens
and Actinomyces uiscosus
Increased Capnocytophaga spp.
Increased black-pigmented anaerobic rods
(particularly Pre uotella intermedia)
Increased black-pigmented anaerobic rods
(particularly l? intermedia)
Increased Capnocytophaga spp. and Actinomyces
naeslundii
gen. Upon fertilization and implantation, the corpus
luteum continues to produce increasing amounts of
estrogen and progesterone while the placenta de-
velops. The placenta, aside from providing nutrition
to the fetus, serves as an endocrine organ that regu-
lates the progress of the pregnancy. By the end of
the third trimester, progesterone and estrogen reach
peak plasma levels of 100 ng/ml and 6 ng/ml respec-
tively, which represents 10 and 30 times the levels
observed during the menstrual cycle (72) (Fig. 3).
This increases the potential biological impact of es-
trogen and progesterone on the periodontium dur-
ing this period.
Kaunitz et al. (28) reported that embolism and hy-
pertensive disease of pregnancy, obstetric hemor-
rhage and infection are the most common causes of
death in a survey of 2475 maternal deaths that oc-
curred in the United States between 1974 and 1978
excluding abortive outcomes. In addition, Hess &
Hess (22) stated that pregnancy by itself posed vari-
able risks of morbidity and mortality to even young
FSH
I 1 I I I 1 1 1 , l l . l l l l l
0 4 8 12 Weeks
Rogss!wone
I I I I I , I I I . I I I , I I I I I I ~
0 4 8 12 Weeks
FIRST
TRIMESTER
Fig. 3. Changes in hormone levels during pregnancy. FSH:
follicle-stimulating hormone; LH: luteinizing hormone;
HCG human chorionic gonadotropin
Hormones and the Deriodontium in women
Correlated with
Tanner index (breast) (19)
Papillary bleeding index (45)
Pre-clinical gingivitis (45)
Pre-puberty (14)
During puberty (70)
Onset of puberty (in insulin-dependent diabetic
children) (18)
and healthy women. Hemorrhage, eclampsia and in-
fection were found as common obstetric risks and
heart disease as an important nonobstetric cause of
maternal death. Brabin (8) found that changes in
maternal susceptibility to infection in early gestation
result from gestational changes in the immune sys-
tem. Andriole & Patterson (3) noted that during
pregnancy, the urinary tract undergoes profound
physiological changes that facilitates the develop-
ment of symptomatic urinary tract infections in
women with bacteriuria. The periodontium is an-
other one of the several tissue compartments that is
potentially affected (10). Robinson & Amar (57) re-
viewed the influence of pregnancy on the oral cavity
and described 4 oral pathological conditions that in-
cluded gingivitis, pregnancy granuloma, peri-
odontitis and dental caries.
Pregnancy gingivitis
Pregnancy gingivitis is a descriptive term for gingi-
vitis occurring during pregnancy (Fig. 4). Epidemio-
logical studies of pregnancy gingivitis show a preva-
lence ranging from 35% (21) to 100% (40). The pat-
Delivery tern of pregnancy gingivitis seems to follow the
hormonal cycle. It initially increases with rising
gonadotropin levels, and is maintained from months
4-8 (with rising estrogen and progesterone levels)
and then falls off in the last month of pregnancy with
the abrupt decrease in hormone secretion (37).
A number of investigations have demonstrated
that the hormonal influence on the immune system
Weak8 contributes significantly to the etiology and patho-
genesis of pregnancy gingivitis. Sridama et al. (62)
demonstrated a decreased CD4/CD8 ratio during
SECOND THIRD
TRIMESTER TRIMESTER pregnancy, and O'Neil (49) showed that peripheral
blood lymphocytes have a decreased in vitro re-
sponse to a number of mitogens including prepara-
tions of I! intermedia. Furthermore, a decrease in
81
Amar & Chung
functional migration of inflammatory cells and
fibroblasts was demonstrated by Senelar & Bureau
(59). A shift in the subgingival microflora has been
attributed to elevated levels of progesterone and es-
trogen.
Kornman & Loesche (32) showed that, during
pregnancy, increased levels of progesterone and es-
trogen paralleled gingival conditions and pro-
portions of I! intermedia. The shift of microorgan-
isms, represented by an increasing anaerobic-to-aer-
obic ratio, is a result of change in the subgingival
microenvironment caused by an accumulation of ac-
tive progesterone, whose metabolism is reduced
during pregnancy (48) and the ability of P interme-
dia to substitute an essential growth factor, vitamin
K (33),with progesterone and estrogen. Jansen et al.
Fig. 4. Clinical presentation of pregnancy gingivitis (cour-
tesy of Alan Berkson, Milford, CT)
Fig. 5. Clinical presentation of pregnancy granuloma.
Note the presence of microbial plaque at the gingival
margin.
Fig. 6. Clinical presentation of pregnancy granuloma.
Note the overhanging restoration, a trap for plaque ac-
cumulation.
(25) demonstrated a 55-fold increase in the pro-
portion of P intermedia in pregnant women com-
pared with the nonpregnant controls. This suggests
that progesterone plays a major role in the shift in
microorganisms.
In an immunohistochemical study, Raber-Dur-
lacher et al. (55) suggested that increased CD4-posi-
tive cells found in oral and sulcular epithelium dur-
ing experimental gingivitis in pregnant women may
belong to the Th-1 subset. This subset of CD4 cells
are known to be cytotoxic to human leukocyte anti-
gen class I1 antigen-bearing cells (B cells and macro-
phages), which may result in diminished immunore-
sponsiveness during pregnancy gingivitis. Further-
more, the Th-1 subset mediates delayed-type
hypersensitivity and its cytotoxicity to B-cells may
Fig. 7. Hematoxylin and eosin section of pregnancy granu-
loma showing similar histological features to pyogenic
granuloma: stroma of myxoid connective tissue; intense
infiltration of polymorphonuclear leukocytes mostly, with
lymphocytes and plasma cells; and increased vascularity
consisting of numerous thin-walled and dilated capil-
laries.

reduce the production of antibodies against such
bacteria as I? intermedia. This may, in turn, serve as
another contributing factor that explains the in-
creased levels of J? intermedia. Looking at the clinical
presentation of pregnant women, Raber-Durlacher
et al. (54) noted that the periodontal pocket bleeding
index increased during pregnancy compared with 6
months postpartum. In addition, O’Neil (49) demon-
strated that progesterone causes an increase in vas-
cular permeability, polymorphonuclear leukocytes
and prostaglandin E2 in the gingival sulcus. Taken
together, the effects of the immunosuppressive in-
fluence of progesterone, increased levels of active
progesterone in the gingiva and microbial shift to-
wards increased proportions of J? intermedia can ex-
acerbate gingival response to microbial plaque in
pregnant women.
Although a significant proportion of pregnant
women suffer from pregnancy gingivitis, this con-
dition is both self-limiting and transient. Gingival
tissues return to their original healthy state postpart-
um when estrogen and progesterone levels reach
baseline values. The ratio of anaerobic to aerobic
microorganisms increases during the second tri-
mester. This is followed by a reversal of these par-
ameters in the third trimester (32). This reversal
trend seems to parallel that observed in pubescent
females. However, women who are susceptible or
have a pre-existing gingival condition should seek
treatment to prevent extension of the inflammatory
process into deeper structures of the periodontium,
which can lead to periodontitis.
Pregnancy granuloma
Pregnancy granuloma is also known as pregnancy
tumor and epulis gravidarum (Fig. 5 ) . However, preg-
nancy granuloma is the preferred terminology since
its histological presentation is similar to that of pyo-
genic granuloma (53) (Fig. 7). Its reported frequency
ranges from 0% (66) to 9.6% (4). This lesion has a
predilection for the maxilla, and in particular the an-
terior vestibular aspect (Fig. 6). It usually presents as
pedunculated soft interdental tissue with a fiery red
color and often covered with small fibrin spots. The
lesion undergoes rapid growth initially but is rarely
larger than 2 cm. Pregnancy granulomas bleed read-
ily if disturbed and demonstrate a tendency to recur
following incomplete removal (35). The cause of
pregnancy granuloma can be attributed in part to
the general effects of progesterone and estrogen on
the immune system and especially the progesterone-
induced inhibition of collagenase superimposed on
Hormones and the periodontium in women
vascular changes. These events result in the accumu-
lation of collagen within the connective tissue, there-
by providing a possible additional mechanism for
the dramatic gingival enlargement of pregnancy
granuloma, and the vascular effects account for the
bright red appearance and hyperemia and edema for
the gingival enlargement. If left untreated, the lesion
will either regress or develop into a residual fibrous
mass postpartum. Laser surgical excision of the
lesion is recommended, as opposed to scalpel, for
less postsurgical bleeding (52). Surgical removal is
usually performed after parturition. However, if the
lesion causes functional problems or appears to
have deleterious effects on the adjacent periodon-
tium, it can be safely removed under local anesthesia
throughout a normal pregnancy, preferably during
the second trimester.
Periodontitis and dental caries in pregnancy
Jonsson et al. (26) demonstrated no significant dif-
ferences in total bacterial counts or proportion of J?
intermedia in pregnant women compared with non-
pregnant women who demonstrated attachment
loss. No significant difference was noted in the
prevalence of periodontitis in pregnant and non-
pregnant women (8,24).However, some periodontal
changes have been observed in pregnant women.
These include a reversible increase in tooth mobility
caused by changes in the periodontal membrane
(56). These studies seem to suggest that the hor-
monal variation during pregnancy has little impact
on periodontitis in pregnant women compared with
nonpregnant women. In reference to dental caries,
studies have yet to show that pregnant women ex-
perience an increased risk ( 5 ) .
Effect of pregnancy on the periodontium
Estrogens, progestins and gonadotropins interrelate
to maintain the menstrual cycle. Estrogens influence
the cytodifferentiation of stratified squamous epi-
thelium, causing keratinization of vaginal mucosa.
Estrogen also appears to be involved in the synthesis
and maintenance of fibrous collagen. Progesterone
has the opposite effect, causing increased vascular
permeability, an increase in polymorphonuclear
leukocytes and prostaglandin E2 in the gingival sul-
cus (49). However, in the clinical situation, aside
from a transient increase in bleeding, gingivitis and a
subgingival microbial shift, pregnant women in good
health are unlikely to experience any significant gin-
gival response that would have serious clinical impli-
83
Amar & Chung
cations. Although pregnant women with peri-
odontitis may not experience exacerbation of their
periodontal condition, it would be prudent to seek
treatment to avoid periodontal abscess formation
that may cause bacteremia. In general, pregnant
women should note that preventive measures con-
sisting of dental prophylaxis and meticulous plaque
control help to prevent any periodontal condition
from developing.
Management of pregnant women
Pregnancy is not a disease state, but special con-
sideration is required in the dental management of
pregnant women. Physical changes include in-
creases in heart rate, cardiac output, red cell mass,
respiratory vital capacity, oxygen consumption and
respiratory rate. Increased energy demands by the
fetus and increased snacking by the mother may el-
evate insulin requirements, unmasking a prediabetic
state. The safety of the developing fetus is also of
concern, and treatment should be planned for times
when the fetus is least affected. Because organogen-
esis occurs mainly in the first trimester, most devel-
opmental defects take place during this time. Most
medication appears to cross the placental barrier,
and fetal exposure to compounds through the inges-
tion by the mother is the second most common
cause of teratogenesis. Central nervous system de-
pression with narcotics use and spontaneous abor-
tions have been reported following nitrous oxide ad-
ministration. Nonsteroidal anti-inflammatory drugs
may interfere with the closure of the arterial duct
if taken during the third trimester (9). Additionally,
tetracycline, vancomycin and streptomycin should
be avoided because of staining of teeth (4-9
months), and ototoxic and nephrotoxic effects. Ery-
thromycin, penicillin and cephalosporins are con-
sidered safe, but consultation with the patient’s ob-
stetrician is recommended before prescribing any
drug. Lynch et al. (41) suggested that due consider-
ation must be given to physical changes in preg-
nancy and the prenatal effects of antibiotics. The
drug selection requires balancing the seriousness of
the infection with the antibiotic’s safety and anti-
microbial activity.
As the fetus continues to grow, the mother’s blad-
der and abdominal vessels are impinged upon and
the diaphragm is displaced upward, reducing respir-
atory volume. Although emergency treatment can be
accomplished any time during pregnancy, the sec-
ond trimester is considered the best time to render
treatment, since organogenesis is complete and the
84
mother is not as uncomfortable as during the first
and third trimesters. Radiographic exposure to the
fetus is nil if proper technique and equipment is
used ( 2 ) . Single films for aid in diagnosis and/or
treatment are, therefore, acceptable.
Contraceptives
Hormonal contraceptives are based on the use of
gestational hormones inducing a hormonal con-
dition that simulates a state of pregnancy to prevent
ovulation. However, the use of oral contraceptives
carries a number of significant implications for the
health of women. Kelleher (29) reviewed the risk of
cardiovascular disease faced by oral contraceptive
users and discussed epidemiological studies that
demonstrate that oral contraceptives increase the
risk of both arterial and venous thromboembolic dis-
ease; the progesterone component is responsible for
arterial events and estrogen for both. Women who
use oral contraceptives show increased plasma levels
of several clotting factors that are related to the dose
of estrogen. The increased levels of Factors VIIc and
XIIc, which causes a state of hypercoagulability, is
significant because, in men, the levels of Factor VIIc
and fibrinogen are strongly and independently re-
lated to ischemic heart disease.
A number of studies (42) have shown various ef-
fects of contraceptive influence on gingival tissue. el-
Ashiry et al. (15) found an increase in clinically as-
sessed inflammation for women using oral contra-
ceptives, and Lindhe & Bjorn (36) observed an in-
creased amount of gingival exudate following 12
months of regular use of oral contraceptives. Pank-
hurst et al. (51) demonstrated a statistically signifi-
cant increase in gingival inflammation related to the
duration of oral contraceptive use. In addition,
women using oral contraceptives had a higher mean
gingival inflammatory index than control subjects
who were not using contraceptives (27). However,
Knight & Wade (30) did not find any significant dif-
ferences in Plaque Index and Gingival Index scores
and attachment level between women using oral
contraceptives and controls but noted that women
using oral contraceptives for more than 1.5 years
tended to have higher Gingival Index scores and
more loss of attachment.
These results suggest that prolonged use of oral
contraceptives may detrimentally affect the peri-
odontium. More studies are required to determine
the underlying mechanisms involved with these
findings. It seems that the periodontal implications

for oral contraceptive users are minimal compared
with the implications of increased risk of cardio-
vascular disease.
Menopause and postmenopause
There is currently controversy over the risk versus
benefit of estrogen replacement therapy. A review by
Barrett-Connor (6) discusses the issue of meno-
pause, which affects 470 million women aged 50
years and above around the world. Estrogen replace-
ment therapy for menopausal women reduces the
risk of osteoporotic fracture by 50% and may prevent
heart disease by up to 50%. However, its unopposed
application is accompanied by a 200-300% increase
in the risk of endometrial cancer (11).Long-term es-
trogen treatment has been found to correlate with
an increased risk of breast cancer (20). The serious
implications of unopposed estrogen replacement
continue, even years after it has been discontinued.
A review by Styrt & Sugarman (63) sounded another
caution that the clinical implication of estrogen ther-
apy on the incidence and outcome of infection
needs to be better defined in light of the immuno-
logical side effects of estrogen. Progesterone in pro-
tective doses has been suggested as part of a combi-
nation therapy, but no consensus has yet been
reached (69). However, progesterone causes signifi-
cant physical, mental and metabolic side effects, in-
cluding regular withdrawal bleeding with cyclical
progesterone.
Kritz-Silverstein & Barrett-Connor (35) showed
that elderly women reporting early menopause or
fewer reproductive years have a higher incidence of
osteoporosis and significantly lower bone density.
However, the level of serum estrogen seems to vary
between different ethnic and sociogeographic
groups. Indeed, Shimizu et al. (60) showed that rural
Japanese postmenopausal women had 43% and 27%
higher levels of estrogen and estradiol after weight
adjustment than their white American counterparts.
A number of studies have linked menopause with
some periodontal conditions. Moshcil’ et al. (46)
demonstrated that women with functional disorders
of the ovaries experienced increased severity of peri-
odontal disorders together with reduced mineral
density of the mandible compared with healthy
women with normally functioning ovaries. Moshcil’
et al. (46) suggested a potential correlation linking
ovarian dysfunction, which could parallel meno-
pause, and lowered bone density of the mandible
with an increased incidence of periodontal disease.
Hormones and the periodontiurn in women
Groen et al. (17) found that the incidence of peri-
odontitis correlates with signs of generalized osteo-
porosis. Another study of 85 osteoporotic women
(34) demonstrated a significant correlation between
skeletal bone mass and the number of teeth remain-
ing in the mandible. But a positive cause-effect re-
lationship between tooth loss from periodontitis and
osteoporosis has yet to be demonstrated. In contrast,
Elders et al. (16) investigated 286 women from a ran-
dom sample of 1200 aged between 46 and 55 years
(9%menopausal and 86% postmenopausal), exclud-
ing those who had hysterectomy, oophorectomy, re-
nal failure, metabolic bone disease or a history of
urolithiasis or used contraceptives or postmenopau-
sal hormonal supplements. No relationship was
found between clinical parameters of periodontitis
and bone mass parameters. Taken together, these re-
sults show that, although osteoporosis in women is
not an etiological factor in periodontitis, it may af-
fect the severity of the disease in pre-existing peri-
odontitis. Women on hormonal replacement therapy
experience problems similar to those of oral contra-
ceptive users. Thus, menopausal and postmenopau-
sal women in good gingival health cannot be con-
sidered to be at increased risk of periodontal disease.
Conclusion
Both progesterone and estrogen affect the oral cavity
significantly. Fortunately, healthy women experience
minimal and transient side effects from variation in
hormone levels. In fact, an epidemiological study
(58) found no significant difference in periodontal
microflora between men and women. In addition,
females have demonstrated a better oral condition
than males. Furthermore, Addy et al. (1) found that
girls consistently had lower plaque, bleeding and
pocketing scores than boys within the same social
class and age group (11-12 years and 15-16 years).
Finally, Bhat (7) noted in a group of 14- to 17-year-
olds in the United States that the boys consistently
had a higher proportion of gingival bleeding on
probing and approximately 3% higher prevalence
rates for supra- and subgingival calculus accumu-
lation than girls in each age group examined. These
results suggest that girls may be more conscientious
and consistent about oral hygiene than boys, thereby
explaining the lack of correlation between puberty
and periodontal clinical parameters in girls.
It seems that, for most healthy young women, the
negative influence of the changes in estrogen and
progesterone levels can be controlled by additional
85
Amar & Chum
plaque control. However, women with pre-existing
gingival conditions or susceptibility to periodontal
disease may experience an exacerbated response to
bacterial plaque if they are pregnant, use oral contra-
ceptives, have hormonal replacement therapy or un-
dergo menopause. Taking into account the effects of
hormonal changes and their corresponding impact
on the periodontium, proper periodontal evaluation
and treatment for these women is recommended.
Acknowledgement
We would like to thank John R. Kalmar for pro-
fessional assistance and for providing appropriate il-
lustrations.
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