|
| A) | 25% | ||
| B) | 45% | ||
| C) | 85% | ||
| D) | 95% |
Symptoms of perimenopause can persist for weeks, months, or years, and symptom severity varies greatly. An early sign of perimenopause is irregular or prolonged menstrual bleeding that can become severe. As estrogen levels decline, vasomotor symptoms, including hot flashes and night sweats (hot flashes with drenching sweats), can also occur. These symptoms can interfere with sleep, which in turn can cause exhaustion, irritability, and altered mood. Up to 85% of people experience hot flashes with widely varying intensity and frequency [1].
| A) | Depression | ||
| B) | Insomnia | ||
| C) | Incontinence | ||
| D) | Increased libido |
Many people will also experience non-vasomotor symptoms, including:
Anxiety
Depression
Difficulty with concentration and/or memory
Headaches
Incontinence
Insomnia
Irritability and mood swings
Joint pain
Loss of libido
Tiredness
Vaginal dryness
| A) | On average, a person loses up to 10% of bone mass. | ||
| B) | Most people maintain bone mass density during this period. | ||
| C) | Bone mass initially increases by up to 5%, but later decreases to premenopausal levels. | ||
| D) | None of the above |
The reduction in estrogen levels that occurs with menopause accelerates age-related bone loss. It is estimated that, on average, a person loses up to 10% of bone mass in the first five years after menopause [1].
| A) | Natural hormones used in compounded products must be converted to the active form in a laboratory. | ||
| B) | Compounded bioidentical hormone replacement therapy is a "natural alternative" to traditional hormone replacement therapy. | ||
| C) | The term bioidentical simply indicates that the hormone has the same chemical and molecular structure as the endogenous hormone. | ||
| D) | Due to a lack of oversight, these compounded products carry a risk of under- or overdosing, lack of sterility, and the presence of impurities. |
Some patients may ask about compounded bioidentical HRT as a "natural alternative" to traditional HRT. However, this is a misconception. The term bioidentical simply indicates that the hormone has the same chemical and molecular structure as the endogenous hormone. Many of the prescription hormones that are approved by the U.S. Food and Drug Administration (FDA) for the management of vasomotor symptoms in menopause are also bioidentical. And although some of the hormones used in compounded products may be derived from natural sources, these natural hormones must still be converted to the active form in a laboratory [22].
In most cases, the dosing of compounded bioidentical HRT is based on unvalidated hormone testing, often using serum, salivary, or urine samples. The use of these tests to guide HRT dosing has not been validated in clinical research and is generally considered unreliable due to natural inter- and intra-individual variations in hormone levels [22]. Additionally, due to a lack of oversight, these compounded products carry a risk of under- or overdosing, lack of sterility, and the presence of impurities.
| A) | 31 years | ||
| B) | 45 years | ||
| C) | 51 years | ||
| D) | 65 years |
RECOMMENDED DIETARY ALLOWANCES OF CALCIUM AND VITAMIN D BY AGE AND SEX
| Population | Recommended Daily Dietary Allowance |
|---|---|
| Vitamin D | |
| Persons 1 to 70 years of age | 600 IU (15 mcg) |
| Persons 71 years of age or older | 800 IU (20 mcg) |
| Calcium | |
| Women 19 to 50 years of age | 1,000 mg |
| Women 51 years of age and older | 1,200 mg |
| Men 19 to 69 years of age | 1,000 mg |
| Men 70 years of age and older | 1,200 mg |
| A) | Taking calcium with vitamin D can increase the risk of CVD. | ||
| B) | The risk of CVD is indirectly proportional to the dose of calcium. | ||
| C) | Calcium supplements may be associated with a small increased risk of CVD, although research is conflicting. | ||
| D) | The Women's Health Initiative study attributed the risk of CVD to hormone replacement therapy, not calcium supplements. |
There has been some concern that calcium supplementation may increase the risk of cardiovascular disease (CVD) in postmenopausal adults. Although meta-analyses of high-quality clinical research have not confirmed an association between calcium supplementation and CVD in the general population, a meta-analysis of research in postmenopausal adults did find that taking calcium for two to seven years, often in amounts over the RDA, increases the risk of CVD and coronary heart disease by 1.1–1.2 times when compared with control. However, many of these studies have been criticized for excluding patients who were also taking vitamin D, and other clinical research has not confirmed this finding [3].
| A) | The recommended daily intake of calcium and vitamin D can often be met through the diet. If the diet provides adequate amounts of these nutrients, supplements are not necessary. | ||
| B) | It is often helpful to take calcium supplements to ensure adequate intake of this nutrient in the diet. Consider taking calcium 500 mg three times daily; vitamin D supplements are not necessary. | ||
| C) | The recommended daily intake of calcium and vitamin D can often be met through the diet. In fact, vitamin D supplements may cause serious health issues when taken long-term and should be avoided. | ||
| D) | It is often helpful to take calcium and vitamin D supplements to ensure adequate intake of these nutrients. To reduce the number of pills needed, consider taking calcium 1,000 mg and vitamin D 20 mcg as a single dose daily. |
There are many different calcium supplements available on the market. Some of these supplements provide calcium alone, whereas others combine calcium with vitamin D. Although the body needs vitamin D to adequately absorb calcium, it is not necessary for vitamin D to be taken at the same time [3].
Calcium supplements are available in various salt forms, some of which provide greater amounts of elemental calcium. For example, calcium carbonate contains 400 mg of elemental calcium per gram, whereas calcium citrate contains 211 mg of elemental calcium per gram. The RDA for calcium is based on elemental calcium [3].
There may also be questions regarding the absorption of different calcium salts. For example, some early research suggested that calcium citrate may be better absorbed than calcium carbonate. However, a follow-up study using a highly sensitive tracer method found no significant difference in the absorption of calcium from either calcium citrate or calcium carbonate. Additionally, calcium from milk seems to be absorbed similarly to the calcium from supplements [3].
The active transport system for calcium in the small intestine is easily saturated. Thus, calcium supplements are typically divided into two doses daily to increase absorption. It is also usually recommended to take it with food in doses providing no more than 500 mg elemental calcium [3].
In order to ensure appropriate calcium intake, educate patients on the difference between elemental calcium and calcium salt content. Also, encourage them to take calcium supplements with food in divided doses.
Vitamin D supplements are available in two forms—D3 (cholecalciferol) and D2 (ergocalciferol). Although the RDA assumes that these forms are equivalent, some evidence suggests that vitamin D2 is less than one-third as potent as vitamin D3. Therefore, many experts now specifically recommend vitamin D3 [4].
For most patients, daily supplementation of 400–1,000 IU (10–25 mcg) is adequate to meet daily requirements. In fact, the BHOF recommends daily intake of 800–1,000 IU (20–25 mcg) for adults older than 50 years of age [4,6].
Except in patients with confirmed vitamin D deficiency, caution against the regular use of very high doses. Over the long-term, regular use of high doses, such as those above the tolerable upper intake level of 4,000 IU (100 mcg) daily, can increase the risk of serious adverse effects such as hypercalcemia, kidney stones, and azotemia. Toxicity typically occurs when blood levels exceed 150 ng/mL [4].
| A) | 32 mg | ||
| B) | 100 mg | ||
| C) | 320 mg | ||
| D) | 800 mg |
The daily RDA for magnesium is 320 mg for those 31 years of age and older. Many foods are rich in magnesium (e.g., whole grains, dark-green, leafy vegetables) and will allow most patients to attain this RDA [7].
| A) | Adequate daily protein intake of about 1 gram/kg, or about 20–25 grams of protein per meal, may help combat age-related muscle loss. | ||
| B) | Consumption of about 500 mg (about five cups of coffee) daily can limit calcium losses and reduce the severity of vasomotor symptoms. | ||
| C) | Moderate alcohol intake (two drinks per day) has been found to reduce the frequency of vasomotor symptoms. | ||
| D) | Proton pump inhibitors (PPIs) should be avoided in order to reduce the risk for calcium deficiency, which can impact bone health. |
Due to concerns regarding age-related muscle loss, adequate protein intake is also important after menopause. The RDA for protein in all adults 18 years of age and older is 0.8 grams/kg. However, the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) actually recommends a higher protein intake for women older than 50 years of age. This recommendation calls for 1–1.2 grams/kg. This comes out to about 20–25 grams of protein per meal [8].
Moderate alcohol intake, which is defined as 0.5 to 2 alcoholic beverages per day, does not seem to have detrimental effects on BMD. However, alcohol intake in amounts greater than two drinks per day can be detrimental to bone health.
There is conflicting evidence on other possible long-term effects from regular alcohol use. While some research indicates that moderate alcohol intake may have health benefits, other research suggests that it may increase the risk for certain conditions. In general, encourage patients to limit alcohol intake. Some experts recommend reducing intake to no more than 0.5 to 1 drink per day.
There have been reports of increased severity of hot flashes with alcohol use. This association has not been evaluated in prospective research, but patients may consider reducing alcohol consumption and monitoring symptoms to determine whether this improves quality of life.
Caffeine increases the excretion of calcium in the urine. At excessive doses, this might affect bone health. According to evidence reviews conducted in the United States and Canada, healthy adults with adequate calcium intake are not at increased risk for decreased BMD, osteoporosis, or fractures as long as daily caffeine intake is limited to 400 mg (about four cups of coffee) [10].
| A) | the risk of serious injury outweighs any potential benefits. | ||
| B) | evidence supporting the use of acupoint modalities is unclear. | ||
| C) | acupuncture has been definitively shown to reduce hot flashes but not other menopause symptoms. | ||
| D) | moxibustion and acustimulation are the modalities with the greatest evidence supporting efficacy. |
Acupoint therapies, which utilize concepts based in traditional Chinese medicine, have grown in popularity over recent years. These include acupuncture, acupressure, moxibustion, and acustimulation.
Although there is general interest in the use of these therapies for the management of menopause-associated hot flashes, only acupuncture has been studied for this purpose, and the research thus far is inconclusive. While some research suggests that acupuncture may reduce hot flash severity, other studies have not supported this finding. Also, a large clinical study evaluating the use of electroacupuncture, administered in 24 separate treatment sessions over eight weeks, found no benefit for symptoms of menopause, although patients did experience a modest improvement in quality of life [11].
| A) | Depression | ||
| B) | Hot flashes | ||
| C) | Sleep quality | ||
| D) | Vaginal dryness |
Most research suggests that mindfulness improves sleep quality, although it might not be beneficial for other measures of insomnia and may not be more beneficial than other nonpharmacologic modalities.
A meta-analysis in patients with insomnia shows that mindfulness meditation improves total wake time and sleep quality, but not sleep onset latency, total sleep time, or sleep efficiency, when compared with control. Another meta-analysis of randomized controlled trials in adults with insomnia shows that practicing MBSR or modified MBSR for six to eight weeks improves sleep quality when compared with receiving education or CBT. A secondary analysis of a clinical trial in generally healthy adults also shows that practicing MBSR for eight weeks improves sleep scores when compared with no intervention, but not when compared with exercise [12].
| A) | Acupuncture | ||
| B) | Mindfulness | ||
| C) | Moxibustion | ||
| D) | Yoga |
Clinical research has found that yoga is beneficial for reducing feelings of perimenopause-related anxiety and depression. Yoga also seems to be beneficial for alleviating menopause-related hot flashes, sleep disturbances, and psychological, somatic, and urogenital symptoms when compared with no intervention. These beneficial effects appear comparable to those seen with other forms of exercise [13].
It is important to note that yoga is also recognized as a form of both muscle-strengthening and balancing exercises, which are recommended for all older adults. Considering that yoga has also shown benefit for the improvement of many menopause-related symptoms, it should be considered as a complementary treatment modality for those in perimenopause and post-menopause.
| A) | Chemicals found naturally in plants that, when purified, have similar potency to endogenous estrogen | ||
| B) | Plant hormones that are bioidentical to human estrogen and can be used as an alternative to hormone replacement therapy | ||
| C) | Plant constituents that, while not structurally related to estrogen, demonstrate weak activity at human estrogen receptors | ||
| D) | A class of plant chemicals, including isoflavones, lignans, and coumestans, that can increase the production of estrogen in humans |
Most of the herbal therapies promoted for symptoms of menopause are classified as phytoestrogens, or "plant estrogens." The three main kinds of phytoestrogens are isoflavones, lignans, and coumestans. Of these, isoflavones are the most potent and also the most common.
Phytoestrogens are not structurally related to estrogen. Instead, they contain a phenolic ring that allows for binding to estrogen receptors. These chemicals are 100 to 10,000 times weaker than endogenous estrogen, and, depending on the tissue type and location in the body, phytoestrogens can act as estrogens or antiestrogens. This is similar to selective estrogen receptor modulators (SERMs) [14].
The estrogenic activity of phytoestrogens also appears to vary with the level of endogenous estrogen. In premenopausal adults with normal endogenous estrogen levels, isoflavones found in soy exhibit an antiestrogen effect, since they can displace endogenous estrogen from receptors. In postmenopausal adults with low endogenous estrogen levels, soy isoflavones are more likely to act as weak estrogens.
| A) | Observational research suggests that the long-term use of soy can increase the risk of breast cancer, although it is unclear if it is associated with endometrial cancer. | ||
| B) | The available clinical and population research suggests that soy does not increase the risk of estrogen-related health issues. | ||
| C) | Most research indicates that soy has no clinically relevant activity at estrogen receptors and is not expected to cause long-term hormone-related health issues. | ||
| D) | Although population research has raised concerns that soy may increase the risk of endometrial cancer, clinical studies show that soy increases the risk of breast, not endometrial, cancer. |
Soy is well tolerated when consumed as part of the diet or as a supplement. The most commonly reported adverse effects are bloating, constipation, diarrhea, and nausea. In postmenopausal adults, specifically, soy isoflavone supplements have also been shown to increase the rate of insomnia.
As with other phytoestrogens, there have been many concerns raised over the years regarding the association between soy intake and the risk for long-term health issues. However, most research in postmenopausal adults indicates that these concerns are not likely to be clinically relevant [14].
Population research has found that soy, as part of the diet or as a supplement, is protective against breast cancer. This research has consistently found that a high-soy diet in Asian and Asian-American women is associated with a reduced risk of breast cancer. However, the amount of soy consumed in a Western diet, even among those who consume the highest amounts of soy, was not found to have a preventative effect [14].
Despite some early research suggesting that soy supplements might stimulate the growth of breast tissue, there does not seem to be a concern for increased risk of breast cancer with the use of soy, even in those with a history of breast cancer. One clinical study shows that taking a tablet containing 50 mg soy isoflavones daily for 12 months does not alter mammographic or breast MRI tissue density in those at high risk of breast cancer, those with non-endocrine-treated breast cancer, or those previously treated for breast cancer and without recurrence [14].
| A) | tamoxifen. | ||
| B) | antidiabetes medications. | ||
| C) | antidepressant medications. | ||
| D) | antihypertensive medications. |
Soy may potentiate the effects of antidiabetes or antihypertensive medications, potentially increasing the risk of hypoglycemia or hypotension. There is also some concern that soy isoflavones, including genistein and daidzein, might antagonize the antitumor effects of tamoxifen. Although research on this topic is conflicting, advise patients requiring treatment with tamoxifen to avoid the use of soy supplements [14].
| A) | fatigue. | ||
| B) | insomnia. | ||
| C) | hot flashes. | ||
| D) | vaginal dryness. |
Multiple clinical studies show that taking S-equol 10–30 mg daily modestly reduces symptoms of menopause, including hot flashes, and improves mood when compared with placebo. Most of this research has been conducted in Japan; however, one clinical trial has evaluated equol in North Americans. In this study, taking S-equol 10 mg, 20 mg, or 40 mg daily for two months resulted in similar reductions in hot flash frequency as a soy isoflavone tablet containing 24 mg daidzein, 22 mg genistein, and 2 mg glycitein. The lack of a placebo group limits the validity of these findings [15].
There is also interest in using equol for various other purposes during menopause, including for improving BMD and reducing facial wrinkles. However, the available research is exploratory, and findings are inconclusive.
| A) | Black cohosh extracts bind to estrogen receptors or upregulate estrogen-dependent genes. | ||
| B) | At least one black cohosh product seems to be comparable to certain forms of hormone replacement therapy. | ||
| C) | Research on the use of black cohosh for vasomotor symptoms of menopause has primarily evaluated generic extracts. | ||
| D) | Clinically, black cohosh appears to affect levels of hormones such as estradiol, luteinizing hormone (LH), or follicle-stimulating hormone (FSH). |
Black cohosh, an herb that is native to eastern North America, appears to have estrogen-like effects, although these effects are exerted via an unknown mechanism. Laboratory research suggests that black cohosh extracts do not bind to estrogen receptors or upregulate estrogen-dependent genes. However, it might have SERM-like activity, exerting estrogenic effects in some tissues and antiestrogenic effects in others. Clinically, black cohosh does not appear to affect levels of hormones such as estradiol, luteinizing hormone (LH), or follicle-stimulating hormone (FSH) [16].
Research on the use of black cohosh for vasomotor symptoms of menopause has primarily evaluated a specific branded product (Remifemin). When taken in doses of 40–127 mg daily for up to 12 weeks, this product reduces symptoms of menopause and hot flash frequency when compared with placebo. It also seems to be comparable to certain forms of HRT, including low-dose transdermal estradiol 25 mcg every week, conjugated equine estrogens 0.625 mg daily, or tibolone 2.5 mg daily [16]. (Tibolone is a synthetic steroid with estrogenic properties that is approved for use in Europe.)
However, research evaluating other proprietary black cohosh extracts has been less consistent. One extract (Klimadynon/Menofem) taken as 40 mg daily for 60 to 90 days does not reduce menopausal symptoms when compared with control groups. However, another extract (Remixin) taken as 40 mg daily for six months modestly reduces hot flashes and night sweats when compared with fluoxetine 20 mg daily. Studies of non-branded black cohosh extracts have been mostly negative, suggesting a lack of benefit on vasomotor symptoms [16].
Although there is speculation that the benefits seen with Remifemin may be due to bias introduced by industry funding, it is also possible that conflicting findings may be related to cultivation and processing methods. Remifemin is standardized across batches to triterpene glycosides, whereas the contents of other products are not clearly defined. Additionally, some non-standardized black cohosh products have been found to contain other species of Actaea, which may have different effects [16].
There is also interest in the use of black cohosh for a variety of other purposes during menopause, such as anxiety, bone health, cognitive function, and cardiovascular risk. However, clinical research to date has shown no benefit for these uses.
| A) | diarrhea. | ||
| B) | headache. | ||
| C) | skin irritation. | ||
| D) | All of the above |
Chasteberry is generally well tolerated, although it has been reported to cause diarrhea, fatigue, headache, insomnia, nausea, skin irritation, stomach pain, and vomiting [17].
| A) | insomnia. | ||
| B) | vaginal bleeding. | ||
| C) | cognitive dysfunction. | ||
| D) | prolongation of the QT interval. |
The most common adverse effect reported with Panax ginseng is insomnia. In postmenopausal adults, specifically, it has also been reported to cause vaginal bleeding. Panax ginseng has also been associated with prolongation of the QT interval when used short-term; its effects when used long-term are unclear [20].
| A) | Black cohosh | ||
| B) | Equol | ||
| C) | Soy | ||
| D) | St. John's wort |
St. John's wort is generally well tolerated but may cause diarrhea, dizziness, dry mouth, mild gastrointestinal discomfort, fatigue, headache, insomnia, and sedation.
This plant is a potent inducer of CYP3A4 and a moderate inducer of CYPs 1A2, 2B6, 2C19, and 2C9, as well as P-glycoprotein. Thus, St. John's wort interacts with many drugs available on the market and should be used with caution in most patients [23].