Text B Diagnosisand Treatmentof Menopausal Symptoms Vasomotor Symptoms

Diagnosis．Vasomotor symptoms are classic manifestations of the menopause transition，and the diagnosis is generally obvious from a woman's age and description of the symptoms．No abnormal physical findings are associated with hot flushes．Estradiol，FSH，and LH levels may be in the normal premenopausal range during the menopausal transition．A woman in her middle 40s to middle 50s who complains of classic hot flushes does not require any specific physical or laboratory evaluation unless there is good reason to suspect another cause of flushing．

Estrogens therapy．Multiple randomized trials have demonstrated that estrogen markedly improves the frequency and severity of hot flushes．All types，preparations，and routes of administration of estrogen are effective． Estrogen reduces the frequency of hot flushes 60％to 95％，depending on the dose．Higher doses of estrogen may control symptoms more rapidly，but they are also associated with a higher rate of side effects，including uterine bleeding，breast tenderness，and headache．

At similar biologically active doses，oral and transdermal，estrogens are approximately equally effective for treatment of vasomotor symptoms．Oral estrogens undergo“first－pass”metabolism in the liver that results in changes in hepatic proteins and enzymes．Hepatic effects are responsible for the beneficial effects of estrogen on lipoproteins（reduced low－density lipoprotein cholesterol and increased high－density lipoprotein cholesterol）but also for potentially adverse effects such as increases in clotting factors．The transdermal route may be safer because it minimizes these changes．

Many estrogen preparations are approved for treatment of vasomotor symptoms．To individualize treatment，physicians should become familiar with several of these preparations．

Treatment with estrogen alone increases the risk for uterine hyperplasia and cancer．The risk for endometrial abnormalities appears not to be increased with the use of vaginal estrogens that deliver low systemic doses，especially if they are used only a few times per week，as is generally recommended．1

Adding aprogestin to the estrogen regimen prevents the increased risk for uterine cancer．For this reason，a woman with a uterus who takes estrogen should also be given a progestin．There is no reason to add progestins to the hormone regimen in women who have had a hysterectomy．Several progestins are approved by the United States Food and Drug Administration（FDA）for this purpose and are available either to add to estrogen or in preparations combined with estrogen．Two general approaches are used to prescribing progestins to protect the endometrium．Sequential therapy（estrogen given daily with a progestin added on the last 10 to 14 days of a 28－day cycle）results in endometrial shedding and cyclic bleeding resembling a menstrual period in approximately 80％of women．Alternatively，the progestin can be added to the estrogen every day． This continuous regimen results in endometrial atrophy and unpredictable uterine spotting or bleeding that can be difficult for the woman to anticipate and manage．2 Bleeding occurs in approximately 80％of women in the first 6 months of continuous treatment．Amenorrhea becomes more common with prolonged use，but some women continue to bleed or spot for many years．

The most commonly used progestins in sequential regimens in women using standard doses of estrogens（0．625 mg oral conjugated estrogens，1 mg oral estradiol，or 0．05 mg transdermal estradiol）are medroxyprogesterone acetate，5 mg and micronized progesterone，200 mg，for 10 to 14 days per month．Continuous regimens generally include half these progestin doses given daily．

The use of bioidentical hormones is based on the concept that estrogens （estradiol，estrone，and estriol）and progestins made from plant products are identical to women's endogenous hormones and more natural，safe，and effective than FDA－approved hormone preparations．3 Bioidentical hormone therapy often uses doses and combinations of steroid hormones guided by patient symptoms or hormone levels．There is little scientific rational for the mixtures and ratios of hormones employed，and there are no adequate clinical trial data to support the safety or efficacy of these regimens，some of which include very large doses of estradiol．Bioidentical hormones are not approved by the FDA for treatment of menopausal symptoms．

Side Effects and Risks

Estrogen is generally well tolerated，but it may cause headache（especially in women with a history of migraine）and breast tenderness．Added progestins tend to make these side effects more severe and also cause uterine bleeding．

The effects of hormone therapy on disease outcomes have been evaluated among postmenopausal women in the Women's Health Initiative（WHI） randomized trials．Both estrogen and estrogen in combination with progestin reduced the risk for hip fracture by 35％to 40％．Neither estrogen alone nor estrogen with progestin reduced risk for coronary events，and both increased the risk for stroke by approximately 40％．

Compared with estrogen alone，added progestin appears to increase the risk for coronary events，pulmonary embolism，breast cancer，and dementia． This finding suggests that adding aprogestin should be avoided，but treatment with unopposed estrogen in women with a uterus markedly increases the risk for uterine hyperplasia and cancer．

The excess risk of any adverse events above in the WHI trials was about 2 per 1，000women treated for 1 year with estrogen in combination with progestin（4．3 per 1，000per year in women older than 65 years if dementia is included）and 0．6 strokes per 1，000women treated with unopposed estrogen． These risks are relatively small，but they cumulate such that treatment for 5 years is associated with an excess risk of one event per 100 women treated with estrogen in combination with progestin and 3 strokes per 1，000women treated with unopposed estrogen．Based on the findings of the WHI trials and the availability of other effective and safe drugs for prevention of osteoporotic fractures，postmenopausal hormone therapy currently has no role for prevention of disease．Some investigators have proposed that estrogen treatment，if started very soon after menopause would reduce risk for coronary disease events．However，careful subgroup analyses of data from the WHI randomized trials do not support this hypothesis．

The mean age of the women included in the WHI trials was 63 years， whereas the average age of women treated for menopausal vasomotor symptoms is approximately a decade younger．Because the risk for most diseases approximately doubles with each decade of age，the absolute risk for the outcomes is less for younger than for older women，and the absolute risk increase is proportionately smaller．However，hormone therapy is relatively contraindicated in women with a history of stroke，breast cancer，or venous thromboembolic events and should be avoided in women at high risk for these conditions．

Other Prescription Drugs

A drug that appears to be as effective as estrogens for treatment of hot flushes is tibolone，a steroid hormone that is not marketed in the United States but is widely available elsewhere．Tibolone preserves bone density，reduces the risks for fracture and breast cancer，but increases risk for uterine cancer and stroke．4 The progestins megestrol and medroxyprogesterone acetate are effective for the treatment of hot flushes，but they have frequent side effects．

Vaginal Dryness

Diagnosis．Diagnosis is primarily based on typical complaints of vaginal dryness，discomfort，itching，or dyspareunia in women undergoing the menopause transition or older postmenopausal women．Pelvic examination should exclude other causes of discomfort，itching infection，lesions，and trauma．Physical findings of vaginal dryness，pallor，friability，and vaginal p H greater than 5．5 support the diagnosis．Cytological examination of the proportion of superficial，intermediate，and parabasal cells from a scraping of the lateral vaginal wall showing primarily parabasal cells also supports the diagnosis．In clinical practice，measurement of p H and vaginal maturation index are not necessary to make the diagnosis．

Treatment．Many women with vaginal symptoms obtain adequate relief with use of over－the－counter（OTC）vaginal moisturizers．Estrogen therapy is highly effective．Topical therapy is efficacious and is preferred because it generally results in smaller increases in systemic estrogen levels than oral or transdermal therapy．

Most clinicians do not add a progestin to protect the uterus in women treated with vaginal estrogen，but evidence to support the uterine safety of vaginal estrogen is limited to short－term studies．Low－dose，intermittent treatment（e．g．1 to 2 g conjugated estrogen cream or 0．025 mg estradiol tablet twice a week）results in very small increases in systemic estrogen levels that appear not to cause endometrial stimulation．However，full－dose daily treatment has been shown to increase estradiol levels to 50 pg／ml or higher in approximately half of treated women and has been associated with uterine 130 bleeding and hyperplasia．5

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New Words and Phrases

randomize［'rændəmaɪz］v． 使随机化；随机取样

preparation［,prepə'reɪʃən］n． 制备；制剂

transdermal［træns'dзːməl］a． 经皮的

metabolism［mɪ'tæbəlɪzəm，me－］n． 新陈代谢

low－density lipoprotein（LDL） 低密度脂蛋白

cholesterol［kə'lestərɒl］n． 胆固醇

clot［klɒt］n． 凝块；血块v． 使凝块

clotting factor 凝血因子；凝结因子

endometrial［,endəʊ'miːtrɪəl］a． 子宫内膜的

progestin［prəʊ'dʒestɪn］n． 孕激素

hysterectomy［,hɪstə'rektəmɪ］n． 子宫切除；子宫切除术

shedding［'ʃedɪŋ］n． 脱落，蜕落

conjugate［'kɒndʒʊɡeɪt］v． （使）结合

medroxyprogesterone acetate 醋酸甲羟孕酮，安宫黄体酮

［me,drɒksɪprəʊ'dʒestərəʊn'æsɪteɪt］

micronize［'maɪkrənaɪz］v． 使微粉化

estrone［'estrəʊn］n． 雌酮

estriol［'eːstrɪɒl］n． 雌三醇

endogenous hormones 内生激素

steroid［'sterɒɪd］n． 类固醇，甾类化合物

steroid hormone 类固醇激素，甾体激素

migraine［'miːɡreɪn，'maɪ－］n． 偏头痛

embolism［'embəlɪzəm］n． 栓塞，栓塞形成

osteoporotic［,ɒstɪəʊpə'rɒtɪk］a． 骨质疏松（症）的

subgroup［'sʌbɡruːp］n． 亚群，亚组，亚类，亚型

hypothesis［haɪ'pɒθɪsɪs］n． 假设，假说

proportionately［prə'pɔːʃənɪtlɪ］ad． 相称地，成比例地

thromboembolic［,θrɒmbəʊem'bɒlɪk］a． 血栓栓塞的

tibolone［'tɪbəʊləʊn］ 替勃龙（7－甲异炔诺酮）

megestrol［mɪ'dʒestrɒl］n． 甲地孕酮（孕激素类药）

cytological［saɪ'tɒlədʒɪkəl］a． 细胞学的

moisturizer［'mɒɪstʃəraɪzə（r）］n． 保湿剂，润肤霜

topical［'tɒpɪkəl］a． 局部的，外用的

Notes

1．The risk for endometrial abnormalities appears not to be increased with the use of vaginal estrogens that deliver low systemic doses，especially if they are used only a few times per week，as is generally recommended．

参考译文：如按常规用药要求一周几次小剂量阴道给予雌激素，似乎并不会增加子宫内膜变异的危险。

此句是复杂句，that引导定语从句修饰the use of vaginal estrogens；if引导条件状语从句，关系代词as引导定语从句，修饰a few times per week。

2．Alternatively，the progestin can be added to the estrogen every day．This continuous regimen results in endometrial atrophy and unpredictable uterine spotting or bleeding that can be difficult for the woman to anticipate and manage．

参考译文：另外，每日除使用雌激素外还可加用孕激素。这种持续治疗方式会导致子宫内膜萎缩和无法预料的子宫斑或者出现女性难以预期和处理的出血现象。

句中that can be difficult for the woman to anticipate and manage是定语从句，修饰bleeding。

3．The use of bioidentical hormones is based on the concept that estrogens （estradiol，estrone，and estriol）and progestins made from plant products are identical to women's endogenous hormones and more natural，safe，and effective than FDA－approved hormone preparations．

参考译文：使用“纯生物激素”的治疗理念是：由植物萃取物制成的雌激素（雌二醇、雌酮和雌三醇）和孕激素制剂与女性体内的内生雌激素完全相同，并且比美国食品与药物管理局（FDA）批准使用的激素制剂更天然、更安全、更有效。

that引导的定语从句修饰主句宾语the concept；定语从句中，分词短语made from做后置定语修饰从句主语estrogens and progestins。句中identical意为“完全相同的，同一的”。近义短语：be similar to．．．与……相似；be the same as．．．与……相同；be identical with／to．．．与……完全相同

4．Tibolone preserves bone density，reduces the risks for fracture and breast cancer，but increases risk for uterine cancer and stroke．

参考译文：替勃龙能够保持骨密度，减少骨折和乳腺癌的危险，但却会增加子宫癌和脑卒中的危险。

句中preserves、reduces和increases是3个并列谓语。

5．However，full－dose daily treatment has been shown to increase estradiol levels to 50 pg／ml or higher in approximately half of treated women and has been associated with uterine bleeding and hyperplasia．

参考译文：但是，每天足量雌激素治疗会使大约一半接受治疗女性的雌二醇水平升高到50 pg／ml或更高，并可引起子宫出血和子宫内膜增生。

句中full－dose daily treatment是主语，has been shown to increase和has been associated with是两个并列谓语。

Exercises

Ⅰ．Answer the following questions．

1．What kind of risk dose treatment with estrogen alone increase？

2．What kind of symptom may estrogen cause，although it is generally well tolerated？

3．What is vaginal diagnosis primarily based on？

4．Why should a woman with a uterus who takes estrogen also be given a progestin？

5．Why is the use of bioidentical hormones more natural，safe，and effective than FDA－approved hormone preparations？

Ⅱ．Decide whether the following statements are True or False．

1．Higher doses of estrogen may control symptoms more rapidly with no side effects．

2．Treatment with estrogen alone increases the risk for uterine hyperplasia and cancer．

3．It is reasonable to add progestins to the hormone regimen in women who have had a hysterectomy．

4．Both estrogen alone and estrogen with progestin reduce risk for coronary events．

5．In clinical practice，measurement of p H and vaginal maturation index are not necessary to make the diagnosis．