Before menopause, most estrogens are produced in the ovaries. After menopause, the ovaries no longer produce much estrogen and estrogens mainly come from fat tissue. After menopause, higher amounts of estrogen in the blood are linked to an increased risk of breast cancer in women [ 19 ].
For a summary of research studies on estrogen levels and the risk of breast cancer, visit the Breast Cancer Research Studies section.
Studies have shown postmenopausal women with higher blood levels of the estrogen estradiol have an increased risk of breast cancer [ 19, ]. A pooled analysis of data from 9 studies found the risk of breast cancer was twice as high among women with higher levels of estradiol compared to women with lower levels [ 19 ]. However, this measure may be useful in the future [ ]. Body weight is an important example. Estrogen is produced in fat tissue. Scientists have known for about 80 years that the hypothalamus, a region in the brain, is involved in regulating the menstrual cycle and reproduction.
Within the past 40 years, they predicted the presence of neural estrogens, but they did not know whether the brain could actually make and release estrogen. Most estrogens, such as estradiol, a primary hormone that controls the menstrual cycle, are produced in the ovaries. Estradiol circulates throughout the body, including the brain and pituitary gland, and influences reproduction, body weight, and learning and memory.
As a result, many normal functions are compromised when the ovaries are removed or lose their function after menopause. For diseases that may be linked to estrogen imbalances, such as Alzheimer's disease, stroke, depression, experimental autoimmune encephalomyelitis and other autoimmune disorders, the hypothalamus may become a novel area for drug targeting, Terasawa says. The study, published today in the Journal of Neuroscience , "opens up entirely new avenues of research into human reproduction and development, as well as the role of estrogen action as our bodies age," reports the first author of the paper, Brian Kenealy, who earned his Ph.
Kenealy performed three studies. In the first experiment, a brief infusion of estradiol benzoate administered into the hypothalamus of rhesus monkeys that had surgery to remove their ovaries rapidly stimulated GnRH release. The brain took over and began rapidly releasing this estrogen in large pulsing surges. In the second experiment, mild electrical stimulation of the hypothalamus caused the release of both estrogen and GnRH thus mimicking how estrogen could induce a neurotransmitter-like action.
Third, the research team infused letrazole, an aromatase inhibitor that blocks the synthesis of estrogen, resulting in a lack of estrogen as well as GnRH release from the brain. Together, these methods demonstrated how local synthesis of estrogen in the brain is important in regulating reproductive function.
The reproductive, neurological and immune systems of rhesus macaques have proven to be excellent biomedical models for humans over several decades, says Terasawa, who focuses on the neural and endocrine mechanisms that control the initiation of puberty. Alarmingly, after the age of 65, one out of every three women has some form of CVD.
Women undergoing the menopause transition or menopausal changes seek medical counsel for a variety of reasons. Absent or irregular menses, insomnia, depression, cephalalgia, and vasomotor instability are just a few of the reasons women visit their physicians.
Many women access information about menopause through a variety of sources including friends, family, Internet sources, television and other forms of media, which may not be accurate sources of information.
The initial evaluation by the health care provider should include a comprehensive history and physical examination accompanied by select laboratory studies and patient education. In addition, family, social, sexual, and medication histories are imperative. A complete physical examination might provide diagnostic clues to a woman's menopausal state. For example, a loss of height might suggest osteoporosis and a pelvic examination might reveal vaginal atrophy from lack of estrogen.
Baseline laboratory studies should also be performed including a screening thyroid stimulating hormone. During the menopause transition, FSH levels fluctuate, making a serum level unreliable for diagnostic purposes. Although in this setting, a FSH evaluation is rarely needed to confirm the postmenopausal state.
If a woman has taken oral contraceptives during the perimenopausal period, she must be taken off them for several months before an accurate FSH level can be determined. Serum estradiol levels fluctuate in perimenopausal women, making it a test that is seldom useful in diagnosing menopause. Testosterone and dehydroepiandrosterone levels are indicated only if a woman has symptoms of hyperandrogenism or if she is taking over-the-counter hormones that may contain these potent androgens.
Various organizations provide recommendations regarding the treatment of menopause. The North American Menopause Society guidelines contain some of the most accurate and clinically relevant information. Women should be educated about the risks and benefits of HT and consider it based on personal risk assessment and quality of life issues.
There are certain situations during which the use of HT is not recommended. Absolute contraindications to HT include pregnancy, an active venous thrombosis or embolism, undiagnosed vaginal bleeding, active liver disease, active breast or endometrial cancer, and active CVD.
Relative contraindications to HT include a history of previously treated breast or uterine cancer, previous thromboembolism, gall bladder disease, uncontrolled hypertension, migraine headaches, uterine fibroids, seizure disorders, hypertriglyceridemia, and a history of CVD.
When considering the use of HT, risks and benefits must be individualized. There is an increased risk of developing thromboembolism associated with HT use. It is estimated that the incidence of deep venous thrombosis or pulmonary embolus occurs in 3 of 10, HRT users annually, especially during the first year of therapy. This risk is present regardless of the form of hormonal or transdermal estrogen used.
A more recent randomized trial revealed a higher incidence of VTE in HT users, specifically in women who were older in age and overweight or obese, or both. In the estrogen-only arm of the WHI, conjugated equine estrogens had less risk for VTE than the combination estrogen- progestin regimen. The type of estrogen a woman takes may also influence her risk for VTE.
However, the U. An increase in the incidence of gallbladder disease is noticed in women on HT. The risk of developing endometrial adenomatous hyperplasia, a precursor for endometrial cancer, occurs in women with a uterus who are on estrogen therapy ET alone unopposed estrogen. Current therapeutic regimens recommend that women on HT with intact uteri receive combinations of estrogen and progestin. This decreases the risk of endometrial cancer to baseline.
The degree of risk, however, is quite controversial. Various studies have shown that HT is associated with an increased risk of breast cancer, but others have not concurred. Short-term HT, used to treat menopausal symptoms, appears not to increase a woman's chance of developing breast cancer.
However, women on HT for more than 5 to 10 years are calculated to have less than one extra occurrence of breast cancer per 1, women. There are no prospective, randomized controlled studies showing that women on HT are more likely to die of breast cancer.
The estrogen only arm of the WHI showed no increased risk of breast cancer in women with a hysterectomy in taking estrogen alone. In fact, women adherent to conjugated estrogen showed a reduced risk of breast cancer. After 15 years of use, however, ET was associated with an increased risk for breast cancer.
HT is effective in the treatment of hot flashes and is currently the only FDA-approved therapy. HT has also been shown to improve symptoms of anxiety, irritability, and depression associated with menopause. Hormone therapy is FDA-approved for the prevention and management of osteoporosis. A woman must continue HT indefinitely to sustain the bone protective benefits. In the WHI, impressive reductions in all types of fractures were seen.
Most women take HT for less than 2 years; therefore, women with osteoporosis, low bone density, or both need alternative treatments. In addition to taking estrogen, it is recommended that women take 1, mg of calcium a day.
If a woman is not on HT, or is older than 65 years, 1, mg of calcium daily is recommended. A clinical practice guideline for osteoporosis appears on the National Osteoporosis Foundation website.
HT has been shown to improve the symptoms of vaginal atrophy in the intravaginal, oral, and transdermal forms. The effects of HT have been controversial in the literature.
Observational studies have suggested a decreased risk of developing Alzheimer's dementia; however, HERS data found that older women with coronary artery disease on HT scored worse on verbal fluency tests and had worse cognition than women taking placebo.
In addition, the WHI memory study revealed that HT did not prevent mild cognitive impairment and, in fact, doubled the relative risk of dementia, suggesting that, like CVD, timing is important. HT and ET have no effect on ovarian cancer risk. Estrogen is given orally, vaginally, or transdermally. Signs and symptoms of urogenital or vaginal atrophy can be assessed by visual inspection at the routine pelvic examination every 1 to 2 years.
Women should be queried regarding complaints of sexual dysfunction, vaginal dryness, and dyspareunia.
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