Physiology of menopause
Review of literature
Oral health, menopause and hormone replacement therapy
Oral symptoms and hormone therapy
Periodontal health and menopause
Periodontal health and hormone replacement therapy
Salivary glands, saliva and menopause
“A woman must wait for her ovaries to die before she can get her rightful personality back. Post-menstrual is the same as pre-menstrual; I am once again what I was before the age of twelve: a female human being who knows that a month has thirty days, not twenty-five, and who can spend every one of them free of the shackles of that defect of body and mind known as femininity.” ― Florence King
Women are the second creator of the world after god. She is responsible for life on our planet Earth. So, such an important creature, woman and her health is an important issue. Women health refers to the total well being of a woman. A woman’s health condition reflects in the whole family. She is the whole and sole care taker in a family.
Women have the right to enjoyment of the highest attainable standard of physical and mental health. The enjoyment of this right is vital to their life and well-being and their ability to participate in all areas of public and private life. Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity. Women's health involves their emotional, social and physical well-being and is determined by the social, political and economic context of their lives, as well as by biology. However, health and well-being elude the majority of women. A major barrier for women to the achievement of the highest attainable standard of health is inequality, both between men and women and among women in different geographical regions, social classes and indigenous and ethnic groups. In national and international forums, women have emphasized that to attain optimal health throughout the life cycle, equality, including the sharing of family responsibilities; development and peace are necessary conditions.
The oral health status of women is becoming an increasing concern in health professions' education, research, and clinical practice.
In a woman`s life at middle age, during the climacteric process, circulating sex hormone levels change and this understandably results in some clinical effects, i.e. climacteric symptoms, which also affect the quality of life. Therefore in the climacterium and post-climacterium, hormone replacement therapy which consists of administration of estrogens, progestins, and estrogen-progestin combinations, is used to alleviate climacteric complaints and also to prevent age-related diseases.
Oral health means much more than healthy teeth, and the relationship between oral and general health has been shown (WHO 2010). The majority of pain and discomfort in the oral cavity is due to diseases of the mouth. However, there are situations where oral symptoms are a consequence of systemic diseases or systemic alterations in physiological conditions.
Oral discomfort is found in many menopausal women. The principal peri- and postmenopausal oral symptoms are dry mouth, sensation of painful mouth of several causes, and less frequently burning mouth syndrome.
Burning mouth syndrome (BMS) is also known as glossodynia, since the tongue is most frequently affected. BMS is characterized by burning oral mucosal pain without any visible signs of mucosal pathology. This pain also does not follow the anatomy of peripheral nerves.
Unpleasant symptoms connected to menopause are treated with hormone replacement therapy (HRT). HRT is widely used to relieve those symptoms in order to increase the well-being of the women treated. HRT is also used to prevent age-related diseases such as cardiovascular diseases and osteoporosis. The benefits as well as side-effects of HRT are well documented.
Profile studies on HRT users have indicated that these women are more health-conscious than non-users. Therefore, the hypothesis of the present study was based on the idea that women who had chosen to take HRT in the first place were those who also had better oral health and health habits in general.
More than one third of Indian women are at menopause and they will live average of 25 to 30 more years. Symptoms are more frequent in perimenopausal age group. Although being an easily accessible mucosal cavity, the oral cavity is usually not checked by gynaecologist. Therefore, dentists treating this large number of patients need to be mindful of both systemic and oral diseases that are prevalent among this group as well as stresses that may be associated with this phase of life. Hence need was felt to evaluate the prevalence of oral manifestations in perimenopausal women by conducting an epidemiological survey.
Dentists have an opportunity to refer women who are not under the care of gynaecologist for an evaluation to determine appropriateness of hormone replacement therapy for its systemic and oral health benefits.
Many systemic diseases have oral manifestations, either along with general symptoms or preceding them. Through this study, if some correlation can be established between the generalized symptoms and oral manifestations of this stressful transitional phase in the lives of many a female; it will certainly help in their management; it may even help in early detection of some of the more serious consequences associated with this stage of life. Therefore, this study was conducted.
Listed below are some brief definitions for the terms that are used in this dissertation.
Sex steroid hormones
Female sex hormones are estrogen and progesterone. They are responsible for physiological changes in the different stages of a woman’s life, and are feminizing in their action. The ovaries secrete estrogens, small amounts of androgens and progesterone. During pregnancy progesterone is responsible for preparing the uterus for the pregnancy.
Male sex hormones, generically known as androgens [testosterone, androstenedione, dehydroepiandrosterone(DHEA)], are responsible for masculinization. The testes secrete large amount of androgens, mainly testosterone, but they also secrete small amounts of estrogens.
Androgens are also secreted from the adrenal cortex in both sexes.
Steroidal estrogens are a group of steroid compounds. The main naturally occurring estrogens in women are estrone (E1; after menopause, estrone levels increase, possibly due to increased metabolism of androstenedione to estrone), estradiol (E2; the primary estrogen from menarche to menopause) and estriol (E3; produced during pregnancy by the placenta).
Non-steroidal estrogens are compounds which possess estrogenic activity, eg. phytoestrogens and xenoestrogens.
Progestagens (progestogens, gestagens ) are a group of naturally occurring (eg. progesterone) as well as synthetic (progestins) hormones having a pregnane skeleton. Progestagens are precursors of other steroids
Plaque-induced periodontal diseases are divided into two general categories based on whether epithelial attachment loss has occurred or not
Periodontal disease is categorized as gingivitis based on the presence of gingival inflammation without any loss of connective tissue attachment and where the junctional epithelium remains at its original level and attached to the tooth.
Periodontal disease is categorized as periodontitis in situations where there is gingival inflammation at sites where there has been pathological detachment of collagen fibers from cementum and the junctional epithelium has migrated apically. In addition to these inflammatory events, which are associated with connective tissue attachment loss, the resorption of coronal portions of tooth-supporting alveolar bone occurs.
Different indices have been developed to be used for quantifying the amount and severity of different oral diseases or conditions in individuals or populations. Some indices are mainly used in clinical practice, while other indices are used in epidemiological surveys.
Physiology of menopause 2,3
At birth, ovaries contain more than 2 million primordial follicles, each containing a single ovum. The majority of these follicles and ova, however, do not develop fully, so that by puberty there are only about 300,000 follicles. During the reproductive years (between 13 and 46 years of age), more than 299,000 of these follicles degenerate steadily (a process called “atresia”). The remaining 400 or so follicles mature into vesicular follicles and expel an ovum each month under the influence of various hormones.
Approximately every 28 days, the hypothalamus in the brain secretes gonadotropin releasing factor which stimulates the anterior pituitary gland to secrete follicle stimulating hormone or FSH. This promotes the growth of vesicular follicle, which when mature produces estrogen. The estrogen and the FSH promote maturation of ovum and thickening of uterine lining. Anterior pituitary gland then secretes luteinizing hormone or LH which assists in further maturation of ovum and its release from the follicle into fallopian tubes.(Fig 1).
The follicle is now devoid of its ovum and it further enlarges. It is then transformed into a glandlike structure called corpus luteum. Progesteron is then secreted by corpus luteum and it further promotes a thickened, well vascularized uterine lining called endometrium. It is capable of nourishing fertilized ovum if conception occurs. If conception does not occur, corpus luteum involutes and stop secreting estrogen and progesterone. The lining of the uterus breaks down and is discharged through the vagina during the process of menstruation.
illustration not visible in this excerpt
Figure 1- Physiology of menopause
Peak ovarian function occurs before the age of 30 years and then declines gradually. The menopause transition also known as climacteric or perimenopause, is defined as the months and years surrounding the last menstrual period.2
The menopause transition is precipitated by fewer functioning follicles and ova, a consequent reduction in the estrogen level and an inability to respond to pitutary gonadotropin releasing hormone, follicle stimulating hormone and lutenizing hormone. The initial sign of transition begins at around 40 years of age when there is reduction in menstrual flow. This is usually followed by missed periods. Menopause is ceasation of menstrual flow for 1 year(amenorrhea) which occurs at the mean age 51 years.
Menopause is a physiological process typically occuring in fifth decade of life in women and involving permanent ceasation of menstruation.
Women, who smoke or women who are thin tend to experience an earlier menopause, while those who are over-weight experience menopause later because of availability of estrogen in adipose tissues.
Review of literature
According to the policy of the WHO Oral Health Programme, oral health is integral and essential to general health. A major theme of the CAPP-report is that oral health means much more than healthy teeth. WHO defines oral health as follows: “Oral health implies being free of chronic oro-facial pain, oral and pharyngeal (throat) cancer, oral tissue lesions, birth defects such as cleft lip and palate, and other diseases and disorders that affect the oral, dental and craniofacial tissues, collectively known as the craniofacial complex”. We often take the function of these oral tissues for granted, although dysfunction of any of these tissues destabilizes our well being. The major functions of these tissues are to allow humans to speak, smile, smell, taste, touch, chew, swallow and cry out in pain. Humans also use oral tissues to convey their feelings and emotions through facial expressions. In addition, oral tissues provide protection against microbial infections and environmental insults.1
Dental caries and periodontal diseases are considered the most important global oral health threats, and losing the teeth is still seen by many people as a natural consequence of ageing. However, according to WHO reports there has been a positive trend, as tooth loss among adults has decreased in recent years. The distribution and severity of oral diseases and unfortunately the access to oral health services vary markedly in different parts of the world and even within the same country and region.2
The mouth or oral cavity is situated at the beginning of the gastrointestinal tract and it is a complex organ with various soft and hard tissue anatomical structures. The condition of the oral cavity can be seen as a reflection of the general health of the individual. Changes due to diseases, such as diabetes or vitamin deficiency, or the local effects of long-term tobacco or alcohol use, are seen as alterations in the oral mucosa.
The major role of the oral mucosa is to protect the underlying structures from mechanical damage and from the entry of some microorganisms and toxic materials that may be present in the oral cavity. The soft tissues of the human oral cavity and esophagus are covered by a stratified squamous epithelium . The oral mucosa is tightly attached to the underlying collagenous connective tissue, called lamina propria.4
In the oral cavity, mucosal regions differ from each other in their thickness, form, and state of epithelial maturation.5
In those regions that are subject to mechanical forces and associated with mastication (i.e., the gingiva and hard palate), the mucosa is covered by a keratinizing epithelium. In some regions of the oral cavity, aging causes slight thinning of the epithelium, with concomitant flattening of the epithelial-connective tissue interface. In female patients aging has also been shown to decrease permeability to water in the mucosa of the floor of mouth.6
Thompson et al in 2001, observed that the patterns of surface keratinization and the distribution and appearance of the lipid lamellae in the intercellular spaces were similar in vaginal and buccal epithelial samples of postmenopausal women. The lipid composition of the two epithelia was similar, except for the cholesterol esters and glycosylceramides, which were more abundant in buccal epithelium. The response of oral epithelia to hormones and HRT is not clear.7
However in an earlier study, Mateo P et al in 1959, corelated any variation in cellular activity of stratified squamous epithelium of gingiva with different phases of menstrual cycle. He found a notable trend towards diminished keratinization which occurs with increasing age.8
WHO has defined three age stages of midlife age for women, Menopause is the year of the final physiologic menstrual period retrospectively designated as 1 year without flow (unrelated to pregnancy or therapy) in women aged ≥ 40 years. 2) Premenopause begins at ages 35 to 39 years; during this stage, decreased fertility and fecundity appear as the first manifestation of ovarian follicle depletion and dysfunction, despite the absence 29 of menstrual changes. 3 ) Perimenopause includes the period of years immediately before the menopause and the first year after the menopause.” A model developed at the Stages of Reproductive Aging Workshop (STRAW) describes seven stages of reproductive ageing.11 (Figure 2)
Diagnosis of menopause is complex as it can be made only retrospectively as menopause is defined as the onset of last menstruation, followed by amenorrhea. Therefore the term “menopausal transition” has been used to refer to the first year of amenorrhea that marks the end of perimenopause and begins the postmenopause phase.12
The term postmenopause is defined as the prolonged period of hypergonadotropic hypogonadism after menopause . Postmenopause is further divided into two different stages: early postmenopause, when estrogen is swiftly declining, and late postmenopause, when prolonged hypoestrogenism exists. Climacterium consists of the transition period from fertility to infertility of which menopause (the last menstruation) as well as perimenopause and postmenopause are parts.13
The endocrine changes during perimenopause manifest as annoying clinical symptoms. The symptoms which may occur before and/or within the first months of menopause are defined as immediate symptoms. Most characteristic for menopause are vasomotor symptoms such as hot flushes and night sweats, which are present in 75-80% of all women in menopausal age groups. Quality of life is greatly reduced because of vasomotor symptoms. Vasomotor symptoms are causally related to decreasing estradiol concentrations, mainly in the serum and subsequently also in the hypothalamic temperature regulating centre. Immediate symptoms have become a leading reason for initiating hormone replacement therapy in clinical practice.14, 15
Other symptoms which are commonly linked to the climacteric stage are mood swings, urogenital dryness, tiredness, joint and muscle pains, dizziness, irritability and insomnia.16 In a Finnish study, 46% of women aged 52-56 years had moderate or severe climacteric symptoms and only 5% were asymptomatic.17
Waugh E J et al in 2009, reviewed previous articles on reduced bone mineral density and data has established an association between low estrogen levels and bone loss.18
Estrogen plays an essential role in the development and maintenance of the skeleton; its effects are mediated via interactions with two estrogen receptor (ER) subtypes, α and β. In 2001, Bord S et al established the cellular distribution of ERα and ERβ in neonatal human rib bone. ERα and ERβ immunoreactivity was seen in proliferative and prehypertrophic chondrocytes in the growth plate, with lower levels of expression in the late hypertrophic zone. Different patterns of expression of the two ERs were seen in bone. In cortical bone, intense staining for ERα was observed in osteoblasts and osteocytes adjacent to the periosteal-forming surface and in osteoclasts on the opposing resorbing surface. In cancellous bone, ERβ was strongly expressed in both osteoblasts and osteocytes, whereas only low expression of ERα was seen in these areas. Nuclear and cytoplasmic staining for ERβ was apparent in osteoclasts.19
The adult skeleton regenerates by temporary cellular structures that comprise teams of juxtaposed osteoclasts and osteoblasts and periodically replace old bone with new. A considerable body of evidence accumulated during the last decade has shown that the rate of genesis of these two highly specialized cell types, as well as the prevalence of their apoptosis, is essential for the maintenance of bone homeostasis; and that common metabolic bone disorders such as osteoporosis result largely from a derangement in the birth or death of these cells.20
Estrogen defficiency is considered to be a major factor predisposing to osteoporosis. For years, experts have recommended HRT as a first-line therapy to prevent trabecular and cortical bone loss in postmenopausal women. Wells et al in 2002, reviewed 57 studies that randomized postmenopausal women to HRT or a control (placebo or calcium/vitamin D) and data showed that HRT has shown a bone strengthening effect both in the spine and hip after 2 years of treatment. Estrogen use has been associated with a reduction of osteoporotic fractures of up to 40-59%.21
In 2001, Maarten L W et al studied women aged between 47 to 54; to investigate the relationship between climacteric symptoms and menstrual pattern during menopausal transition in a population based cross sectional survey. He found that hot flashes are strongly associated with the transition of premenopause to perimenopause, while urogenital complaints, day time sweating and insomnia are more prevalent with transition from perimenopause to postmenopause.24
Sudhaa S et al in 2007, conducted a cross sectional study among 117 urban women with natural menopause to evaluate the correlation of age on these symptoms by interviewing regarding their menopausal complaints. The study revealed, varying nature of symptoms with age and MDSM (Mean Duration since Menopause), with vasomotor symptoms being more prevalent with lesser MDSM and psychological and rheumatic complaints more prevalent with increasing age and MDSM in this region.25
Cardiovascular diseases (CVD) are rarely diagnosed in premenopausal women compared with age-matched men. However, menopause has been known to be associated with the incidence of CVD. Menopause is known to induce hypoestrogenism and this has been suggested to be one of the explanatory factors for this association.30
In 2001, Arthur et al assessed panoramic radiographs of 52 neurologically asymptomatic menopausal women for atheromas in carotid arteries. The radiographs of 16 menopausal women (31%) exhibited atheromas located in the neck, 2 cm inferior and posterior to angle of mandible. So he concluded that some neurologically asymptomatic menopausal women are at high risk of developing stroke and can be identified in the dental office via panoramic radiography.45
Psycho somatic status at menopause
In 1930, George R et al stated that the majority of women pass through the climacteric with its psycho-physiological adjustments with great discomforts. Of the psychotic syndromes at the climacteric, melancholia is by far the most common.22
Previous studies have found increased rates of depression in women aged 45 to 54 years, but the factors that influence these rates are not understood. In 2001, Hayden B et al collected data from 581 women between ages of 45 years to 54 years for depressive symptoms at menopause. Depression was measured with the abbreviated CES-D, a depressive symptoms screening measure. There were 168 women (28.9%) who reported a high level of depressive symptoms when the abbreviated CES-D was used. In a logistic-regression analysis, significant factors associated with increased depressive symptoms included physical inactivity, inadequate income, use of estrogen/progesterone combination, and presence of climacteric symptoms (trouble sleeping, mood swings, or memory problems).23