Periodontal treatment of female patients

Periodontal treatment of a female patient presents a unique challenge to clinicians because of the effect of variations in hormonal levels on oral soft tissues. Hormonal variations during the lifetime of a female patient during puberty, pregnancy, on the usage of oral contraceptives and menopause may cause worsening of the existing periodontal disease resulting in loss of periodontal support of the teeth. To render adequate periodontal treatment to female patients, it is important to thoroughly understand the hormonal variations that occur during their lifetime, starting from puberty till menopause.

Biological functions of estrogen and progesterone

Estrogen and progesterone are the two main female hormones which influence the health of periodontal tissues. These hormones exert significant effects on different organ systems by affecting cytodifferentiation of stratified squamous epithelium, and the synthesis and maintenance of fibrous collagen 1. Vittek et al. (1982) 2, for the first time, reported the presence of specific estrogen receptor in the gingival tissue.

The estrogen receptors present in osteoblast-like cells respond to the estrogen, thus directly affecting the bone metabolism. These receptors are also present on periosteal fibroblasts and periodontal ligament fibroblasts by which estrogen exerts a direct effect on periodontal tissues 3. Estrogen and progesterone along with chronic gonadotropin hormone play a key role during pregnancy. Progesterone has a major role in the preparation of endometrium for implantation of a fertilized ovum. The ovum implantation is facilitated by progesterone by the synthesis of enzymes responsible for lysis of the zona pellucida. Estrogen, progesterone, and chorionic gonadotropin hormone have a……………..

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Effects of sex steroid hormones on gingival tissue in females

As already stated, sex steroid hormones directly or indirectly affect the cellular proliferation, thereby influencing the growth and differentiation of gingival keratinocytes and fibroblasts 8, 9. Both estrogen and progesterone have a variety of cellular, vascular and immunological effects on periodontal tissues. These effects have been illustrated in Table 30.1

Table 30.1 The cellular, vascular and immunological effects of female sex hormones on periodontal tissues

Estrogen
Progesterone
Androgens
• Decreases keratinization while an increase in epithelial glycogen resulting in the diminution in the effectiveness of the epithelial barrier
• Stimulates the proliferation of the gingival fibroblasts
• Stimulates the synthesis and maturation of gingival connective tissues
• Increases the amount of gingival inflammation with no increase in plaque
• Increases cellular proliferation in blood vessels
• Stimulates PMNL phagocytosis
• Inhibits PMNL chemotaxis
• Suppress leukocyte production from the bone marrow
• Inhibits proinflammatory cytokines released by human marrow cells
• Reduces T-cell mediated inflammation
• Inhibits proliferation of human gingival fibroblast proliferation
• Inhibits collagen and non-collagen synthesis in periodontal ligament fibroblast
• Alters rate and pattern of collagen production in gingiva resulting in reduced repair and maintenance potential
• Increases the metabolic breakdown of folate, which is necessary for tissue maintenance and repair
• Increases vascular dilatation, thus increases permeability
• Increases the production of prostaglandins
• Increases PMNL and prostaglandin E2 in the
• gingival crevicular fluid (GCF)
• Reduces anti-inflammatory effect of glucocorticoids
• Enhance matrix synthesis by periodontal ligament fibroblasts and osteoblasts
• Inhibit prostaglandin secretion
• Enhance osteoblast proliferation and differentiation
• Reduce IL-6 production during inflammation

Estrogen stimulates the synthesis and maturation of gingival connective tissue by up-regulating the proliferation of gingival fibroblasts 10. On the other hand, progesterone inhibits the proliferation of human gingival fibroblast 9 thereby altering the rate and pattern of collagen production, which adversely affects the repair and maintenance of connective tissue 11. Progesterone causes vascular dilatation and increased vascular permeability and estrogen causes increased cellular proliferation in blood vessels. These changes increase the vascularity of gingiva. Increased estrogen levels are associated increased gingival inflammation without any increase in plaque accumulation 12. Progesterone increases the folate metabolism, which is required for cellular maintenance and repair 13. Its increased metabolism can deplete folate stores and inhibit tissue repair 9. Progesterone also alters collagen metabolism, thus down-regulating tissue repair. Progesterone has been shown to increase the production of prostaglandin E2, a pro-inflammatory mediator. It also enhances the accumulation of polymorphonuclear leukocytes (PMN’s) in the gingival sulcus by enhancing chemotaxis of PMN’s 14. On the other hand, estrogen stimulates PMN mediated phagocytosis 15 but inhibits PMN chemotaxis 16. Estrogen also downregulates T-cell mediated inflammation 17. These hormones have also been shown to modulate the production of cytokines. It has been demonstrated that progesterone reduces the production of IL-6 by gingival fibroblasts to 50% of that of control values 18, 19. It has also been demonstrated that estrogen and progesterone modulate gingival inflammation by impairing the monocyte functions. Monocytes are involved in the direct immune response by producing IL-1β, TNF-α, IL-6, IL-12, and IL-18 which in turn activate various other cells and processes. In one study monocytes from pregnant women were found to produce more IL-1β and IL-12, and less TNF-α, in comparison to their non-pregnant stage 20. The function of antibody producing cells (B-lymphocytes) seems to remain unaffected during pregnancy 21.

Hence, the changes in the levels of these hormones during the lifetime of females have a significant effect on periodontal tissues. In the following sections, we shall discuss in detail the effects of these hormones on periodontal tissues during various stages in the lifetime of females.

Puberty

The puberty age for females averages between 11 to 14 years. During this period the production of sex hormones (estrogen and progesterone) increase, which remain irregular until postpubertal stabilization of hormones takes place. During puberty, an exaggerated periodontal tissue response has been observed towards periodontal risk factors. There is a lot of evidence in support of a significant increase in gingivitis in children entering puberty and during the pubertal period 3, 22, 23. The enlargement of the gingival tissue is observed in areas with plaque or food debris accumulation. The inflammation of the gingival tissue and its inflammatory enlargement can be seen clinically. The inflamed gingival tissue bleeds easily upon slight provocation.

One of the reasons for this increased inflammation is changes in subgingival microbiota 24, 25. The levels of Prevotella intermedia have been shown to be increased in subgingival microbiota in puberty gingivitis. P. Intermedia can substitute estrogen and progesterone for vitamin K, an essential bacterial growth factor 26, 27. Other bacterial species which have been shown to increase in number in plaque samples from puberty gingivitis patients include spirochetes, Capnocytophaga species, Actinomycetes species, and Eikenella corrodens 3, 28. In general, an increased plaque accumulation has been reported during puberty 29. An increased number of Capnocytophaga species in plaque has been associated with increased bleeding tendency 28. The severity of gingivitis during puberty has been shown to be related more to the amount of plaque accumulation rather than hormones 29. Thus, adequate oral hygiene is a primary requirement in the maintenance of periodontal health in these patients.

Management:

The most important step in preventing puberty related periodontal problems is to educate the patient as well as her parents/caretakers about biological changes in a female during this period. The patient should be motivated to maintain an excellent oral hygiene during this period. Adequate maintenance of oral hygiene itself results in improvement in periodontal condition. In the case of mild to moderate inflammation, scaling and polishing are sufficient to improve the periodontal status of the patient. In the case of severe gingival inflammation, along with scaling and polishing, use of antimicrobial agents for subgingival irrigation and use of mouth rinses is recommended 30.

Another important factor contributing to gingival inflammation in females during puberty is mouth breathing. The incidences of mouth breathing are higher in pubertal females and males. The dehydration of the tissue results in inflammation and enlargement of gingiva. The application of lubricants over the inflamed tissue, especially before going to sleep is helpful in reducing the inflammation of tissue.

Females in the adolescent age group are also susceptible to eating disorders like anorexia nervosa and bulimia nervosa. The patient should be carefully examined for perimylosis……….

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Menstrual cycle

The menstrual cycle consists of ovarian and uterine cycles which are controlled by hormones, including estrogen, progesterone, follicle stimulating hormone (FSH) and luteinising hormone (LH). An average ovarian cycle lasts 28 days, which is interrupted only by pregnancy. The ovarian cycle consists of a follicular phase, which is characterized by maturing ovarian follicles and a luteal phase which is characterized by the presence of the corpus luteum. Both of these phases last for 14 days each. The follicular phase is dominated by the presence of FSH and estrogen, which ensure follicle growth and development. Once, ovulation takes place the luteal phase starts. During this phase, old follicular cells undergo a structural transformation to form the corpus luteum (gland). If the released ovum does not get fertilized and implanted, the corpus luteum degenerates within about 14 days after formation (Figure 30.1).

Figure 30.1 The menstrual cycle and various hormones contributing to it

Menstrual cycle

The uterine phase reflects the hormonal changes in the uterine wall during the ovarian cycle. The average time duration of this cycle is 28 days. It consists of three phases: menstrual phase, proliferative phase, and secretory or progestational phase. The menstrual phase lasts 5-7 days and is characterized by the discharge of blood and endometrial debris from the vagina. The first day of menstruation is considered as the start of the new cycle, which reflects the onset of new follicular phase in the ovarian cycle. The menstrual phase is triggered by decreased estrogen and progesterone levels. The proliferative phase starts concurrently with the last portion of ovarian follicular phase. During this phase, the uterus prepares for receiving the fertilized ovum. This phase is dominated by estrogen. The endometrium of the uterus starts to repair itself and proliferate under the influence of estrogen. This phase lasts from the end of menstruation to ovulation. The secretory or progestational phase occurs under the influence of progesterone and estrogen. The blood supply of the endometrium increases and glands in the uterine wall enlarge and secrete glycogen-rich fluids. Uterus enters this phase after ovulation when new corpus luteum is formed. If fertilization of the ovum takes place, it gets implanted on the uterine wall. If the ovum does not get fertilized, the corpus luteum degenerates and new follicular phase with menstrual phase beginning once again.

Effect of menstrual cycle on periodontium:

The increase in progesterone levels during the menstrual cycle is associated with increased permeability of the microvasculature and increased production of prostaglandins, as a result of which significant inflammatory changes are observed in the gingiva. Inflammatory changes often occur in the interproximal sites and, usually, are significantly greater in molars than in anterior teeth 33-35. The highest incidences of pregnancy-related gingivitis due to increased levels of progesterone have been reported in second 36, 37 or third trimester 33-35, 38. After the delivery, spontaneous recovery of gingival health occurs without any progression to periodontitis.

A gradual increase in production of gingival crevicular fluid is observed during the proliferative phase just before the menstruation, which is associated with increased levels of estrogen and progesterone 39.  Hugoson (1971) 33 demonstrated that gingival exudate increased by at least 20% during ovulation in more than 75% of the females examined. During the luteal phase of menstrual cycle, progesterone concentration reaches its highest levels. The high progesterone levels have been shown to be associated with high incidences of intraoral recurrent aphthous ulcers 40, herpes labialis lesions and Candida infections 41. A minor increase in tooth mobility has also been reported during menstruation 42. The levels of pro-inflammatory cytokines have also been shown to fluctuate during the menstrual cycle, which may be directly or indirectly related to the inflammatory status of gingiva. It has been demonstrated that levels of TNF-α fluctuate during the whole menstrual cycle 43. Progesterone has been found to decrease the production of IL-6 18, 44. Both estradiol (at 20ng/ml) and progesterone (in various concentrations) have been found to be associated with increased PGE2 production 45.

Management:

In a patient with moderate to severe gingival inflammation, scaling and polishing are recommended and the patient should be motivated to maintain a good oral hygiene. In patients with a history of excessive menstrual flow, the surgical procedures are scheduled after cyclic menstruation is over. Female patients should be carefully examined for anemia and if it is found to be present, referral to a physician for its management should be considered.

Pregnancy

If the ovum gets fertilized, it gets implanted in the uterine wall and pregnancy is established. During pregnancy, there are marked changes in the hormonal levels, which exert their significant effects on oral health. After implantation corpus luteum continues to produce estrogen and progesterone while the placenta develops. The plasma levels of progesterone and estrogen reach their peak (100ng/ml and 6ng/ml, respectively) by the end of the third trimester. These levels of progesterone and estrogen are respectively, 10 and 30 times higher than as observed during menstrual cycle 8. The high levels of estrogen and progesterone during pregnancy cause increased vascular permeability thus resulting in clinical signs of gingivitis. This gingivitis is referred to as ‘pregnancy gingivitis’. It has been observed that the prevalence of pregnancy gingivitis ranges from 35% to 100% and may peak during the second trimester of pregnancy 46. The increased prevalence of gingivitis during pregnancy has been observed without any increase in mean plaque index 37, 47, 48. Increased tooth mobility has been reported during pregnancy, which is attributed to the initial free intrasocket movement of the roots 49. The possible reason suggested for the increased tooth mobility is that due to high levels of sex hormones, the vascularity of the periodontal vascular system is increased, resulting in slight edema which causes slight tooth extrusion. This results in slight increase in horizontal tooth mobility 49.

Some studies have investigated the changes in the subgingival microbiota during pregnancy. A shift of the subgingival levels of Prevotella intermedia and other Gram-negative anaerobic microorganisms has been observed during the second trimester of pregnancy 37, 50. In another study, a 55-fold increase in the population of Bacteroides species in pregnant women was demonstrated as compared to the control group 50. Studies have also been done to investigate the presence of viruses in subgingival microbiota during pregnancy. One study demonstrated that the risk of presence of subgingival Epstein Barr Virus (EBV) in pregnant women is 3.647 times more, than in non-pregnant women 51.

Studies have been done on molecular mediators of inflammation during pregnancy. It has been shown that progesterone may control and reduce local production of matrix metalloproteinases, which explains that pregnancy gingivitis may not necessarily progress to periodontitis 52C-reactive protein (CRP) is considered as a highly sensitive but non-specific marker of inflammatory status and is an indirect reflection of infectious burden. CRP levels are higher among pregnant women as compared to non-pregnant women 53. Further, CRP levels have been found higher among women with periodontal disease as compared to periodontally healthy women 54. Many studies have reported that both pregnancy-associated gingivitis and periodontitis act as independent risk factors for preterm birth/low birth weight 55-63.

Another inflammatory lesion associated with pregnancy is  pyogenic granuloma. It has been found to develop in around 0.5-2% of pregnancies 64, 65. It is also referred to as “pregnancy tumor” or “granuloma gravidarum”. It is believed to develop as a result of an exaggerated response to irritation caused by dental plaque 66. It develops mostly during the second to third month of pregnancy and has a high tendency to bleed. With increasing size, it may interfere with mastication. The proposed mechanism of granuloma formation is that during pregnancy, increased levels of estrogen cause accelerated production of nerve growth factor (NGF) by macrophages, granulocyte-macrophage colony stimulating factor (GM-CSF) by keratinocytes and basic fibroblast growth factor (b-FGF) and transforming growth factor-β (TGF-β) by fibroblasts. These result in accelerated granulation tissue formation 67. It has been shown that pregnancy associated pyogenic granuloma tissue expresses significantly more vascular endothelial growth factor (VEGF) and b-FGF than normal healthy gingiva and periodontium 68.

Alteration in immune response during pregnancy:

The most important alteration that occurs during pregnancy is partial suppression of the mother’s cell-mediated immune responses associated with T-helper type 1 (Th1) lymphocytes 69-72. The maternal immune system not only recognizes the pregnancy, but responds in a manner so that no damage is done to the fetus.  The suppression of Th1 associated cell mediated response is an important component of this altered response. On the other hand, the antibody-mediated response is accentuated which is mediated by T-helper type 2 (Th2) lymphocytes 73-75. The cytokine release from these cells is altered i.e. enhanced Th2 dependent (e.g. IL-4, IL-10) and Th3 dependent (i.e. TGF-β) cytokine production and suppressed Th1 dependent (IFN-γ, IL-12) cytokine production. As cytokines are chemical messengers for various cellular activities, these changes affect both cellular and humoral arm of the immune system. Although the exact reason for this change in Th1/Th2 balance in favor of Th2 has not been explained, but increased estrogen and progesterone levels may be responsible for this shift 67, 76, 77. The cytotoxic activity of NK cells is reduced in pregnancy due to increased levels of progesterone, which reduces IFN-γ production from Th1 lymphocytes. The behavior of PMN’s is also altered during pregnancy to provide protection to the fetus from maternal immune response. The respiratory burst 78-81, phagocytosis 82 and myeloperoxidase activity 83, 84 of maternal PMN’s has been shown to……..

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Systemic changes observed during pregnancy:

A dentist should be well versed regarding the systemic changes that occur during pregnancy. Although pregnancy affects the body as a whole, but the effects on the cardiovascular, respiratory and gastrointestinal system should be well known to the dentist.

Cardiovascular system:

The cardiac output, plasma volume and heart rate, all are increased during pregnancy. A benign systolic ejection murmur is present in almost 96% pregnant women, which does not require any treatment 85. This murmur is caused by increased blood flow across the pulmonic and aortic valves. Due to vasomotor instability, the pregnant women are predisposed to postural hypotension. It is of particular importance while seating the patient in dental chair (explained later).

Respiratory system:

The increased levels of estrogen during pregnancy causes increased blood flow in the capillaries in the mucosa of the nasopharynx. It results in edema of mucosal tissue in the nasopharynx causing nasal congestion and predisposition to epistaxis. It may become more difficult for the patient to breath from the nose and there is a tendency for mouth breathing. Mouth breathing causes xerostomia and patients with high caries index may have increased caries incidences. The patient should be treated for caries control if such situation arises 86.

Gastrointestinal system:

The pregnant patients are predisposed to greater sensitivity to gag reflex and gastric acid reflux. The increased progesterone levels during pregnancy cause decrease in lower esophageal tone and gastric and intestinal motility. Along with this, as the uterus size increases, it displaces stomach superiorly which increases the intragastric pressure. So, during dental treatment, the patient should be kept as upright as possible so that abdominal pressure is relieved and the patient is comfortable.

Another problem faced by pregnant women suffering from nausea during pregnancy is ptyalism (excessive salivation). There may not be an actual increase in the amount of salivation but because the pregnant women may not be able to swallow normal amounts of saliva due to nausea, there is a sensation of excessive salivation. Some patients may actually have increased salivation. The intake of complex carbohydrates has been shown to improve the condition in these cases 85.

Dental treatment of pregnant patients

The dental treatment of pregnant patients has always been difficult for clinicians. The reason for this is the pregnant woman’s and her family’s anxiety regarding dental treatment during pregnancy. The lack of proper information, as well as wrong assumptions, make people think that dental treatment during pregnancy may not be safe for the child or the mother. Even some dental professionals avoid dental treatment during pregnancy considering it possibly dangerous for the fetus 87, 88. It must be emphasized here that dental treatment during pregnancy is not only safe, but also necessary and must be delivered according to the patient’s requirements. Ideally, before conceiving during prenatal planning the woman should be referred to consult the dentist.

Positioning pregnant woman in the dental chair:

When a pregnant woman is sitting in supine position on the dental chair, the uterus may put pressure on the inferior vena cava, thus reducing venous return to the heart. It results in reduced cardiac output, which may lead to the hypotensive syndrome. The patient may become unconscious due to reduced blood supply to the brain. It occurs in approximately 15-20% of pregnant females. This problem occurs primarily during late second and third trimester as the uterus size increases sufficiently to compress the inferior vena cava. To prevent this phenomenon, the head of pregnant woman should always be higher than her feet when sitting in a dental chair. A small pillow or folded blanket should be placed under her right hip so that the uterus is displaced towards the left side and does not put pressure on the inferior vena cava 89.

Radiographs during pregnancy:

Regular radiographs do not cause any gross malformations in the developing fetus.  According to guidelines given by the National Council on Radiation Protection and Measurements (United States) (NCRP), 50 mSv radiation exposure to developing fetus does not result in any significant congenital defect 90. However, all the safety measure should be taken to minimize radiation exposure to the fetus, especially during the first trimester. The concept of As Low As Reasonably Achievable (ALARA) should be implemented, as done with all other patients.

Use of medications during pregnancy:

The primary concern regarding the use of medications during pregnancy is teratogenicity. Ideally, no drug should be administered during pregnancy, especially in the first trimester 86. However, many times drug administration is required and almost all the females commonly take one or the other kind of medicine during the pregnancy period. There are many medications which can cross the placental barrier and may reach the fetus. Food and Drug Administration (FDA) has classified various medications into different categories according to their safety when used in pregnancy (Table 30.2). In breastfeeding mothers, the drug may pass to the child through the milk. Unfortunately, we have minimal conclusive information regarding the percentage of drug in the breast milk of female taking standard adult dosage of the drug. Usually, the percentage of drug excreted in breast milk is not more than 2-3% of the maternal dose. Therefore, it is unlikely that many of the drugs can have a significant effect on infant 91, 92. It is recommended that a breastfeeding mother should take the drug just after breastfeeding her child and then avoid breastfeeding for up to 4 hours or more so that the drug concentration in breast milk reduces. Penicillins are considered safest for breastfeeding mothers.

Table 30.2 FDA categories of drugs used during pregnancy

Pregnancy category
Definition
Examples of Drugs
AAdequate, well-controlled studies in pregnant women failed to demonstrate any risk to the fetusFolic acid
Levothyroxine
BNo evidence of risk in humans; animal studies show risk but human findings do not; or animal findings are negative and no adequate human studies have been performedAmoxicillin (safe)
Paracetamol (safe)
Cephalosporins (limited information)
Metronidazole (avoid; carcinogenic data from animals)
Clindamycin (with caution, drug concentrates in fetal bone, spleen, lung, liver)
Chlorhexidine

CHuman studies are lacking and animal studies are either lacking or test positive for fetal risk; however, potential benefits may justify the riskVancomycin (avoid; limited information)
Ciprofloxacin (avoid; cartilage erosion)
Most of the non-steroidal anti-inflammatory drugs (NSAIDs)
Fluconazole
Albuterol
DPositive evidence of risk; investigational or post-marketing data show risk to the fetus; however, potential benefits may outweigh risks (as with some anti-convulsive medications)Tetracycline (avoid; depression of bone growth;
enamel hypoplasia; gray-brown tooth discoloration)
Clarithromycin (Avoid; adverse pregnancy outcomes)
Paroxetine
Phenytoin
Lithium
XStudies on humans and animals show that the medicine when given during pregnancy cause problems in the fetus. These medicines should never be used by pregnant womenThalidomide
Isotretinoin

The safest antibiotic used during pregnancy is amoxicillin and penicillin V 93, 94. Tetracycline should not be used during pregnancy because the drug gets accumulated in fetal dental tissue during the calcification stage, resulting in tooth discoloration 94. Among non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol can be safely used because it is not teratogenic.

Use of local anesthetics:

Commonly used local anesthetic agents during periodontal non-surgical and surgical procedures include lidocaine (2%) and mepivacaine (3%). Most safely used local anesthetic agents during pregnancy are lidocaine, prilocaine, and etidocaine. These drugs fall in B category of the FDA classification, whereas mepivacaine falls in the C category (Table 30.3). These agents can be used in combination with vasoconstrictor. However, the recommended maximum dose of local anesthesias during pregnancy should be well below the maximum recommended dose. The maximum dose for lidocaine is 500 mg. For prilocaine, it is 600 mg and for etidocaine, it is 400 mg.  There is no clear-cut evidence regarding the effect of vasoconstrictor on uterine muscles.

Table 30.3 FDA classification of local anesthetic agents when used during pregnancy

Local anesthetic agents
FDA category
Considerations for use
Lidocaine (2%)BCan be used safely
PrilocaineBCan be used safely
EtidocaineBCan be used safely
Mepivacaine (3%)CUsed only if needed in consultation with obstetrician
BupivacaineCUsed only if needed in consultation with obstetrician
ProcaineCUsed only if needed in consultation with obstetrician
ArticaineCUsed only if needed in consultation with obstetrician

Periodontal treatment:

A careful medical history of the pregnant patient should be recorded and obstetrician should be contacted, if required to discuss the medical status of the patient. Regular oral prophylactic treatments such as scaling and polishing may be performed whenever necessary. Any invasive dental treatment should preferably be done during the second trimester as it is considered to be the safest period for dental treatment. If there is any emergency, dental treatment can be done at any point during pregnancy by taking recommended precautions regarding radiation exposure, operative procedure, and medications.

Trimester periodontal care during pregnancy:

During the first trimester of pregnancy, preventive periodontal therapy is done and home care instructions are given to the patient. As pregnant women are more susceptible to periodontal diseases, a complete periodontal screening is recommended and its importance should be explained to the patient. As during the first-trimester organogenesis takes place, any environmental influence may adversely affect the process of organogenesis. So, elective dental care if possible should be avoided during the first trimester.

The early portion of the second trimester (14–20 weeks of gestation) is most suitable for providing elective dental care. Periodontal debridement aimed at cessation of periodontal disease progression can be carried out during this period. The treatment for pregnancy-associated pyogenic granuloma can be done safely during this period (second trimester). It is treated by conservative surgical removal of the tissue and removal of the causative agents such as plaque, calculus, foreign materials and any other cause of local irritation. However, surgical excision of pyogenic granuloma is sometimes associated with its recurrence due to a combination of poor plaque control and hormone mediated growth of the lesion. The patient should be advised to maintain a good oral hygiene and professional plaque removal and subgingival irrigation are helpful in preventing its recurrence. Laser excision of the lesion is helpful in minimizing bleeding during excision. The surgical removal should preferably be done during the second trimester of pregnancy.  However, major elective oral or periodontal surgical procedures should be postponed until after delivery.

During the third trimester, the uterus is very sensitive to external stimuli and the chances of premature delivery exist. The woman is quite uncomfortable during this time, so prolonged sittings in the dental chair should be avoided. All the precautions should be exercised to avoid supine hypotensive syndrome (already explained). During early or mid of the third trimester a periodontal maintenance visit should be scheduled for the patient to evaluate the periodontal status and provide treatment, if required.

Some patients suffer from a condition called pre-eclampsia during pregnancy. It is a condition where hypertension is associated with proteinuria. This condition is not a contraindication for dental treatment. However, the patient should be carefully examined and only elective treatment should be provided.

Use of oral contraceptives

The use of oral contraceptives started in 1960’s. Initially, high dosage of estrogen and progestin were used in these formulations. The first oral contraceptive contained estrogens (150 μg) and progestins (9.85 mg). The high dosage of hormones was shown to be associated with high risk of cardiovascular events 95. The presently available oral contraceptives contain a low dosage of these hormones. Most of the present-day formulations typically contain estrogen doses of 20-35 μg/day and progestin doses of 0.5-1.0 mg/day.

The periodontal problems in women taking oral contraceptives include elevated inflammatory response to local irritants, mild to severe gingival inflammation and in some cases increased size of gingiva 96. Increased flow of gingival crevicular fluid (GCF) has been reported in women taking oral contraceptives. A study compared the GCF production in women taking oral contraceptives to those who did not, over a period of 12 months. A 50% increased GCF flow was observed in women taking oral contraceptives 96. The oral contraceptives containing estrogen alter the coagulation process and women taking them show greater incidences of clot lysis 97. In a study done on osteitis following extraction of mandibular third molars, it was observed that women taking oral contraceptives were at two times more risk of developing localized osteitis. It is due to the effect of oral contraceptives on coagulation factors 98. Spotty melanotic pigmentation on skin has been reported in some cases with the use of oral contraceptives 99.

Management:

The patient should be informed about the periodontal problems associated with the use of oral contraceptives. Maintenance of adequate oral hygiene and regular dental visits should be advised. In the case of gingival inflammation scaling and root-planing should be performed.

Menopause

Menopause is defined as the cessation of menstrual periods that occurs naturally or is induced by surgery, chemotherapy or radiation 100. These are many hormonal changes that occur after menopause. Due to few remaining follicles in the ovaries, the follicle-stimulating hormone levels rise 10- to 20-fold, and luteinizing hormone levels rise threefold. Their levels gradually rise to maximum up to 3 years after menopause after which there is a gradual decline in their levels 101. There are various changes associated with the changes in hormone levels after menopause. These include disturbance in menstrual pattern, reduced fertility, progression to amenorrhea, atrophy of genitor-urinal tissues, vasomotor instability (hot flashes and sweats), increased cardiac morbidity, osteoporosis, cognitive decline and mood associated symptoms.

The most commonly associated symptoms with menopause are………

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The ovarian changes following menopause also predispose women for mood-related symptoms, including depression, anxiety and/or irritability. However, estrogen therapy in post-menopausal women has been shown to cause mixed results and there is only a weak evidence of improvement in depression or anxiety after estrogen replacement therapy.

Effects of menopause seen in the oral cavity:

There is thinning of gingival and oral mucosal epithelium. The thin epithelial lining may easily get rubbed off which may cause pain in the oral cavity due to any minor trauma such as toothbrushing trauma. The deficiency of estrogen is associated with precipitation of xerostomia. Xerostomia may predispose oral tissue for injury to already thinned gingival and oral tissues. Many reports suggest improvement in oral symptoms following implementation of hormonal replacement therapy, which is primarily due to the increased salivary secretion 108-110. On the other hand, in a study done on 43 healthy pre-menopausal and post-menopausal females, Ship et al. (1991) 111 demonstrated that there was no significant difference between salivary gland function in pre-menopausal and post-menopausal females, suggesting that menopause or hormone replacement therapy does not significantly affect salivary gland function. Farzaneh, et al. (2012) 112 evaluated salivary cortisol levels in post-menopausal women with oral dryness and reported that these levels were in direct proportion to the severity of oral dryness. Taste sensation may also change, causing frequent complaints of a metallic taste 113. Burning mouth syndrome, also known as glossodynia or stomatodynia is also observed more frequently after menopause (Figure 30.2) 114. Other oral symptoms in burning mouth syndrome are dry mouth or alterations in taste sensation 115, 116. The exact reason for burning mouth syndrome is not clear.

Figure 30.2 A post-menopausal patient demonstrating burning mouth syndrome

Burning mouth syndrome

Burning mouth syndrome

One major problem associated with post-menopausal women is osteoporosis. It has been well documented that estrogen depletion after menopause is an important reason for osteoporosis 12 in post-menopausal women. During bone growth, estrogen is needed for proper closure of the epiphyseal growth plates, both in females and in males. The exact mechanism, how estrogen deficiency causes osteoporosis is not completely understood, however, it has been stated that decreased estrogen levels cause more production of TNF-α by immune cells. TNF-α is a very potent osteoclast activating factor which ultimately causes bone resorption.

Various alterations in the oral environment associated with osteoporosis include increased incidences of tooth loss, ridge resorption, inflammatory changes in gingiva and poor wound healing 117. The decreased bone density is an important consideration, when planning for dental implant treatment. The quality of bone is an important factor determining the long-term success of dental implant treatment.

 

Know more…….

Osteopenia and osteoporosis:

Both osteopenia and osteoporosis are characterized by reduction in bone mass and may result in skeletal fragility. According to WHO, osteoporosis is defined as the bone mineral density level more than 2.5 standard deviations below the mean of young, normal women. Osteopenia is a reduction in bone mass due to an imbalance between bone resorption and formation, favoring resorption and resulting in demineralization and osteoporosis.

 

Management:

A thorough case history of the patient should be compiled, followed by intraoral examination and thorough evaluation of mucosal surfaces. The periodontal examination should be done followed by evaluation of salivary flow for both quantity and quality. Whenever required, sialometry can be performed. The patient should be motivated to maintain a good oral hygiene. To prevent the occurrence of dental caries, fluoridated toothpaste, varnishes or gels containing fluorides should be advised.

To treat problems associated with post-menopausal hormonal disturbance many systemic treatments have been suggested. Out of these treatments, most extensively studied treatment is hormone replacement therapy (HRT) by providing external estrogen, often in combination with progestin. Other treatments include treatment with antidepressants, isoflavones and other phytoestrogens, botanicals, acupuncture and behavioral interventions 118.

Hormone replacement therapy (HRT)

Estrogen:

Low-dose estrogen therapy has been used extensively for hormonal replacement. Low dose concentration of estrogen, including ≤ 0.3 mg of conjugated equine estrogen, ≤ 0.5 mg of oral micronized estradiol, ≤  25 μg of transdermal estradiol or ≤ 2.5 μg of ethinyl estradiol have been used clinically. However, it has been demonstrated that estrogen therapy at doses equivalent to 0.625 mg of conjugated equine estrogen increases the risk of stroke, deep vein thrombosis, and pulmonary embolism. Estrogen alone can be given daily as a monotherapy, whereas for combined therapy with estrogen and progestin, there are two types of regimens,

  • Cyclic therapy: Estrogen is taken every day, and progestin is added for several days each month or for several days every 3 months or 4 months.
  • Continuous therapy: Estrogen and progestin are taken every day.

Local estrogen therapy is used for the treatment of vaginal dryness. Estrogen can be applied in the form of vaginal ring, tablet or cream. These agents release a small amount of estrogen in the vaginal tissues which help in restoring the thickness and elasticity of the vaginal wall.

Progestins:

Progestins are used in combination with estrogen in hormonal replacement therapy because there is a conflicting data regarding the efficacy of progesterone alone in for the treatment of hot flashes in post-menopausal women. The pharmacological properties and adverse effects of progestins used in hormonal replacement therapy vary for different formulations of progestin. Presently formulated progestins have anti-androgenic properties which make them free of side effects associated with testosterone-derived progestins.

Other than estrogen and progestin, androgens have also been used in HRT. Dehydroepiandrosterone has also been used but its long-term benefits and side effects have not been evaluated. Tibolone, which has a weak hormonal activity has also been used for hormone replacement. Bioidentical (and natural hormones) refer to a combination of individually compounded recipes of a variety of steroids in various dosage forms for a particular patient. These are formulated based on patient’s salivary hormone concentrations. The combination formulated for an individual patient includes the specific concentration of steroid hormone designed for that particular patient. The combination is formed of components like estrone, estradiol, estriol, dehydroepiandrosterone, progesterone, pregnenolone and testosterone. The data authenticating their safe use for long duration of time is not available and requires further research.

Other medications:

Many other medications that are used for the treatment of problems associated with post-menopausal women include antidepressants, clonidine, gabapentin, methyldopa, and bellergal. These drugs are advised to the patient according to the clinical symptoms and may provide symptomatic relief. Medications derived from various plants have also been used. In this respect, Black cohosh (Actacea racemosa or Cimicifuga racemosa) is the most studied botanical products. However, there is a paucity of adequate research on it.  Other botanical products used include Kava (Piper methysticum), Red clover leaf (Trifolium pretense), Dong quai root (Angelica sinensis) and Ginseng root (Panax ginseng or Panax quinquefolius).

Conclusion

The female hormones play a vital role in influencing their periodontal health and wound healing. From the above discussion, it is clear that female hormones undergo significant changes during the lifetime of a woman.  The changing levels of these hormones significantly affect the systemic and oral health of females. Early identification of oral and systemic problems associated with hormonal changes is required to improve their overall health. So, it is important for an oral health care provider to take into consideration these factors and plan the treatment accordingly.

Periobasics: A textbook of Periodontics and Implantology
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Periobasics: A textbook of periodontics and implantology

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