Clinically speaking, menopause is a date, the day after a woman's final period finishes.
In practice, "menopause" is usually not used to refer to one day, but to the whole of the menopause transition years. This span of time is also referred to as the change of life, the change , or the climacteric and more recently is known as "perimenopause”. The word menopause is also often used in popular to mean all the years of postmenopause (Wikipedia).
The age of menopause has not changed , but there is gradual increase in life expectancy. In previous centuries women were not expected to live beyond menopause, now they spend > one third of their life after menopause.
>31 million women are undergoing menopausal transition in USA.
Menopause is a normal developmental process, but the decline in E can have clinical sequelae.
Cognitive decline and Alzheimer's disease.
Menopause is OK but its sequalae are not OK Hot flashes Osteo, Urogenital CVD Mood Collagen
1.Follicular depletion ("natural" menopause) or
2.Surgical removal of the ovaries ("induced, or surgical," menopause).
The secretion of the ovarian E & P declines.
Menstrual cycles seldom cease abruptly; there is an interval of "perimenopause" or "menopausal transition," during which there are considerable hormonal fluctuations.
Perimenopause begins a few years before last cycle ; the cycles become irregular with symptoms suggesting a decline in E. Perimenopause also extends for a few years after the last menstrual cycle; during this time, transient and episodic bursts of ovarian activity may occur, which may result in some vaginal bleeding.
Climacteric :The time from the decline in reproductive capacity onward.
Reproductive aging occurs rapidly after the third decade, and fecundity is extremely low before menopause.
Both Climacteric and reproductive aging start far before menopause.
Follicular atresia accelerates at about 37.5 years . Thus, reproductive aging precedes menopause by 5-10 years, at a "young" chronologic age. This is signified by an increase in (FSH) level in the early follicular phase of regular cycles and a decrease in the circulating inhibin B level. The elevation in FSH drives the accelerated follicle depletion.
Two estrogen receptors exist: ER-alpha and ER-beta. Various estrogens have different affinities for ER-alpha and ER-beta, which, in turn, have different tissue distributions in the body. For example, in certain regions of the brain (eg, frontal cortex), ER-beta predominates over ER-alpha. In the cerebellum, only ER-beta is expressed. Because ERs are abundant throughout the body, the menopausal decline of estrogen potentially affects virtually all organ systems, so we get:
E has a positive effect on collagen, which is important for bone and skin. The loss of collagen is more rapid in the first few years after menopause, and 30% of skin collagen is lost within the first 5 years.The rate is 2% per year for the first 10 years after menopause. This statistic, is similar to that of bone loss; strongly suggests a link between skin thickness, bone loss, and osteoporosis.
More than one third of women > 65 years suffer from osteopenia/ osteoporosis, a disorder of low bone mass.
E deficiency is a dominant pathogenic factor in bone loss.
From 1.5 years before to 1.5 years after menopause, spine bone mineral density (BMD) decreases by 2.5% per year , compared with a premenopausal loss rate of 0.13% per year.
Loss of trabecular bone (spine) with E deficiency is greater than cortical bone (femoral neck) loss. E deficiency is also a risk factor for alveolar (oral) bone loss in postmenopausal women with a history of periodontitis.
There is an association between reduced BMD and both cardiovascular (CV) mortality and cognitive decline.
In women, peak BMD is achieved by the second decade and begins to decrease thereafter. At menopause, there is 3% reduction in bone mass per year for the first 5 years; thereafter, 1%-2% per year, increasing the risk of fracture.
E action on bone is mediated by direct effects on and by effects on collagen . The accelerated decline in bone mass is mediated by a variety of mechanisms, but the primary event is increased resorption (osteoclastic activity), which becomes uncoupled from bone formation (osteoblastic activity).
There are also indirect effects mediated by parathyroid hormone and cytokines, which oppose the resorptive effects . Osteoprotegin (OPG), is a soluble protein that inhibits osteoclastic bone resorption.
In postmenopause, the positive effects of estrogen on growth factors, calcitonin, vitamin D metabolism, and calcium absorption are also diminished.
CVD in postmenopausal women aged 50-59 was 4-fold higher than in premenopausal women of the same age.
However, the relative risk (RR) of CVD depended on the interval that age was adjusted for (ie, for a 5-year interval, the RR was1.7; for a 1-year interval, the RR was 1.2) as well as on adjustment for smoking .
Aging and E deficiency contribute to the increased risk of CVD in older women.
Premature menopause, <age 35, has 2- to 3-fold increased risk of myocardial infarction; oophorectomy (before age 35) increases the risk 7-fold.
Blood flow in all vascular beds decreases after menopause.
Estrogen and progesterone receptors have been found in vascular tissues, including coronary arteries. Overall, the direct vascular effects that occur after menopause are considered as important as, or more important than, the changes in lipid and lipoproteins in terms of CVD risk.
Carbohydrate tolerance decreases as a result of an increase in insulin resistance.
10% DHEA vaginal cream have beneficial effects, without significant adverse effects, through the transformation of DHEA into androgens and/or estrogens in specific peripheral intracrine tissues. Endometrium remained atrmation.
How can we modify the increased mortality and morbidity rates in our older women patients?
Smoking cessation to prevent lung cancer.
Screen for breast cancer risk factors; family history; fertility or infertility history, and age at menarche, menopause, and first pregnancy. Preventive measures = frequent self-examination and provider examinations; annual mammography in women older than 40 years.
For CVD , assess family history and risk factors as BP, cholesterol , DM, smoking, poor diet, and lack of exercise.
Screen cancer colon, ovary, and uterus.
It is also important to evaluate bone mass . BMD has proved to be very useful.
Calcium and vitamin D are important adjuncts to treatment and preventive health programs.
Vitamin D together with HRT provide a bone-sparing effect that is superior to that of HRT alone.
Calcium should begin before menopause. Calcium carbonate (500 mg daily), in premenopausal women prevent bone loss, allowing them to enter menopause with greater bone mass, which may reduce the risk of later bone fracture.
What is the reason to intervene? Are there symptoms such as hot flushes? The answer is : short-term therapy.
For postmenopausal woman who has no major complaints but is concerned about osteoporosis, for example. Her family history, risk profile, and bone-mass assessment are valuable adjuncts to help decision making.
Depending on these variables, the choice of intervention may be:
Black kohosh, genistein, and soy-based products have been shown to be effective for hot flushes.
Although some data are available for soy-based products, there are no convincing data about efficacy for vaginal health, lowering CVD risk, or improving brain function.
Because phytoestrogens bind to ERs (ER-beta > ER-alpha), large doses (which are needed to achieve benefit on a statistical basis) may pose some risk for estrogen-responsive cancers, such as breast cancer; although, conventional thinking is that these products are protective for the breast.
Bisphosphonates, estrogen, and SERMs slow or stop bone loss but they do not replace bone that has already been lost. Currently in clinical development are a group of bone-building peptides -- native parathyroid hormone, its 34- to 38-amino acid N-terminal fragments, and a group of molecules known as second-generation mini-PTHs. 
Awareness of HRT is determined by race, educational level, and the perception of going or having gone through menopause.
Women selected or self-selected for long-term HRT use tended to be healthy: they were thinner, younger, and physically more active; more were involved in professional work; and more had oophorectomies and experienced earlier menopause than the average postmenopausal woman.
Many women express fear regarding HRT, especially because of the associated risk of breast cancer.
Women believe that the leading cause of death in women is breast cancer. Many also believe that only a small percentage of deaths are attributable to CVD.
The truth, of course, is the reverse. One in 3 women older than 65 years has some evidence of CVD, and the risk of breast cancer after age 65 is 1 in 36. Although it has been widely asserted that the incidence of breast cancer in women is approximately 1 in 8 women, this is the lifetime risk. Age-specific data are quite different, and the risk is 1 in 77 in the fourth decade, 1 in 42 in the fifth decade, and 1 in 45 in the eighth decade.
ET clearly decreases bone turnover and prevents postmenopausal bone loss.
A positive correlation exists between systemic osteoporosis and oral alveolar bone resorption.(Alveolar bone in the maxilla and mandible provides the framework for tooth support.) Estrogen replacement reduces oral alveolar bone loss, increasing the probability of better tooth retention in postmenopausal women.
With estrogen treatment, vaginal cytology can change from a profile of predominantly parabasal cells to one with an increased number of superficial cells. Along with this change, vaginal pH decreases, vaginal blood flow increases, and the electropotential difference across the vaginal mucosa increases to premenopausal levels.
ERT increases venous thromboembolic events (VTEs). The risk of VTEs was higher in the first year of treatment.
In women with a history of thrombosis, there is an increased risk of VTEs with ERT. Women who have a family history of thrombosis or had VTEs with oral contraceptives or other prior ERT should be discouraged.
Vaginal Bleeding, breast tenderness and bloating may also occur but can be alleviated by alterations in dosage and type of preparation.
Unscheduled bleeding in any postmenopausal woman should be investigated regardless of results of US endometrial thickness, because abnormalities may be present when the endometrial thickness is less than 4 mm.
Recurrent bleeding during sequential HRT regimens causes many patients to stop treatment.
Decision model for the calculation of breast cancer risk on the basis of 7 risk factors: testosterone levels, BMI, waist-to-hip ratio, alcohol consumption, density to mammography, previous benign disease, and family history.
Short-term estrogen use (~ 5 years) is not associated with increased breast cancer risk, But controversy surrounds long-term estrogen use (> 10 years).
The positive association was especially pronounced with continuously combined estrogen-progestin combinations.
Bleeding is one of the most common reasons for discontinuance of HRT. Progestins may also cause mood alterations. These side effects have to be dealt with effectively and usually require more flexibility in prescribing habits. It would be prudent to use the lowest dose of progestin necessary to prevent endometrial hyperplasia until more data are available.
Whether or not HRT should be considered is a very individual decision, which must take into account symptoms, risk factors, and individual preferences and needs. Alternatives should always be carefully considered .
If hormonal therapy is chosen, there should be flexibility in prescribing -- there is no ideal regimen for every woman.
Estrogen can be used for short-term treatment of symptoms at the lowest dosage that will adequately control hot flushes or vaginal dryness or dyspareunia.
Recent data support the initiation of HT around the time of menopause to treat menopause-related symptoms; to treat or reduce the risk of certain disorders, such as osteoporosis or fractures in select postmenopausal women; or both. The benefit-risk ratio for menopausal HT is favorable for women who initiate HT close to menopause but decreases in older women and with time since menopause in previously untreated women
The statement suggests that the association between ovarian cancer and HT beyond 5 years , if any, should be considered as rare or very rare, but that women with a positive family history or other increased risk for ovarian cancer should be counseled about this rare association.
Overall data, including those from WHI analysis, suggest that starting EPT in older women with a positive smoking history may promote the growth of existing lung cancers. In contrast, evidence from the WHI and some case-control and cohort studies suggests that use of HT in women younger than 60 years offers some protection against lung cancer.
Although safety of EPT in survivors of breast cancer is controversial, with observational studies suggesting that it is safe and possibly even protective against recurrence, a randomized controlled trial showed a statistically significant 2.4-fold increase in new breast cancer events. ET use in breast cancer survivors has not been proven to be safe and may be associated with an increased risk for recurrence.
HT is currently not recommended as a sole or main indication for coronary protection in women of any age.
Starting HT by age 50 to 59 years or within 10 years of menopause to treat typical menopausal symptoms does not seem to increase the risk for CHD events, and there is some recent evidence that starting ET in early postmenopause may lower CHD risk.
Current data suggest that when HT is either tapered or abruptly discontinued, rates of vasomotor symptom recurrence are similar. The statement therefore makes no recommendation concerning how to discontinue therapy.