For the past two or three years, many of my friends, women mostly in their early 50s, have found themselves in an unexpected state of suffering. The cause of their suffering was something they had in common, but that did not make it easier for them to figure out what to do about it, even though they knew it was coming: It was menopause.

在过去的两三年里，我的许多女性朋友（大多50岁出头）发现自己处于一种意外的痛苦状态。她们的痛苦来源是一样的，但这对找到应对之法并没什么帮助，尽管她们都知道那一天——她们的更年期会到来。

The symptoms they experienced were varied and intrusive. Some lost hours of sleep every night, disruptions that chipped away at their mood, their energy, the vast resources of good will that it takes to parent and to partner. One friend endured weeklong stretches of menstrual bleeding so heavy that she had to miss work. Another friend was plagued by as many as 10 hot flashes a day; a third was so troubled by her flights of anger, their intensity new to her, that she sat her 12-year-old son down to explain that she was not feeling right — that there was this thing called menopause and that she was going through it. Another felt a pervasive dryness in her skin, her nails, her throat, even her eyes — as if she were slowly calcifying.

她们的症状各不相同，令她们不胜其扰。一些人每晚好几个小时都无法睡着，并且会出现各种紊乱，而这些紊乱会一点点破坏心情、消耗精力，为人母、为人妻所需要的那种充沛的善意也在枯竭。有一位朋友忍受了持续整整一周的经血过多，出血程度严重到她甚至无法上班。另一位朋友饱受每日多达10次的潮热之苦。还有一位朋友则备受持续不断的愤怒情绪困扰，由于这种情绪的程度对她来说是不曾有过的，所以她甚至和12岁的儿子坐下来谈了谈，向他解释自己为何会感到不适——有一种东西叫做“更年期”，而她正处于其中。还有一位朋友的皮肤、指甲、喉咙、甚至是眼睛到处都感到十分干燥，就好像她正在一点点钙化一样。

Then last year, I reached the same state of transition. Technically, it is known as perimenopause, the biologically chaotic phase leading up to a woman’s last period, when her reproductive cycle makes its final, faltering runs. The shift, which lasts, on average, four years, typically starts when women reach their late 40s, the point at which the egg-producing sacs of the ovaries start to plummet in number. In response, some hormones — among them estrogen and progesterone — spike and dip erratically, their usual signaling systems failing. During this time, a woman’s period may be much heavier or lighter than usual. As levels of estrogen, a crucial chemical messenger, trend downward, women are at higher risk for severe depressive symptoms. Bone loss accelerates. In women who have a genetic risk for Alzheimer’s disease, the first plaques are thought to form in the brain during this period. Women often gain weight quickly, or see it shift to their middles, as the body fights to hold onto the estrogen that abdominal fat cells produce. The body is in a temporary state of adjustment, even reinvention, like a machine that once ran on gas trying to adjust to solar power, challenged to find workarounds.

然后在去年，我也开始了同样的转变。严格来说，它叫做“围绝经期”，这是女性最后一次经期前的一段生理混乱期，在此期间，女性的生殖周期开始最后的、逐渐衰退的周期。这一转变平均会持续四年，通常在女性年近50岁的时候开始。在这个年龄，卵巢中生产卵子的卵泡开始急剧减少，导致某些激素（包括雌激素和孕激素）出现不规律的飙升和下落，往常的信号系统也在失效。在此期间，女性的月经可能会较往常更多或更少。随着雌激素这种关键化学信使的水平持续下降，女性出现严重抑郁症状的风险也更高，骨质流失会加速。对于有较高阿兹海默症遗传风险的女性，首批大脑斑块被认为是在这个阶段形成的。随着身体努力留住腹部脂肪细胞产生的雌激素，女性的体重往往会迅速增加。女性的身体在这时处于一种暂时的调整期，甚至可以说是重塑期，就像是一个曾经以汽油为动力的机器试图调试到太阳能动力，努力在找寻解决之道。

I knew I was in perimenopause because my period disappeared for months at a time, only to return with no explanation. In the weeks leading up to each period, I experienced abdominal discomfort so extreme that I went for an ultrasound to make sure I didn’t have some ever-growing cyst. At times, hot flashes woke me at night, forcing me straight into the kinds of anxious thoughts that take on ferocious life in the early hours of morning. Even more distressing was the hard turn my memory took for the worse: I was forever blanking on something I said as soon as I’d said it, chronically groping for words or names — a development apparent enough that people close to me commented on it. I was haunted by a conversation I had with a writer I admired, someone who quit relatively young. At a small party, I asked her why. “Menopause,” she told me without hesitation. “I couldn’t think of the words.”

我知道自己进入了围绝经期，是因为我的月经会一下子好几个月都不来，又会毫无预兆地回来。在每次月经前的数周，我会感到腹部极度不适，不适程度严重到我甚至去做了B超确认是不是有不断在增大的囊肿。有时，潮热会让我在半夜醒来，迫使我在凌晨就开始焦虑地思考残酷的人生。更令人烦恼的是记忆力的急剧恶化：每次我只要刚说完什么，转头立刻就忘了，总是在想某个词怎么说或某人的名字是什么——这个新问题实在太明显了，身边人都开始对此发表意见。有一场对话在我心头一直萦绕不去，对方是一位我仰慕的作者，年纪轻轻就辞职不干了。在一场小型派对上，我问她为什么这么早就不干了。“更年期，”她毫不犹豫地对我说。“已经开始提笔忘字了。”

My friends’ reports of their recent doctors’ visits suggested that there was no obvious recourse for these symptoms. When one friend mentioned that she was waking once nightly because of hot flashes, her gynecologist waved it off as hardly worth discussing. A colleague of mine seeking relief from hot flashes was prescribed bee-pollen extract, which she dutifully took with no result. Another friend who expressed concerns about a lower libido and vaginal dryness could tell that her gynecologist was uncomfortable talking about both. (“I thought, hey, aren’t you a vagina doctor?” she told me. “I use that thing for sex!”)

从我的朋友们近期看医生的经历来看，对于这些症状，是没有什么简单直接的办法的。当一个朋友提到自己每晚都会因为潮热醒来时，她的妇科医生表现得仿佛这件事不值一提。我有一位同事想寻求缓解潮热的方法，于是医生给她开了蜂花粉提取物。她按时服用了，却毫无功效。另一位朋友对性欲下降、阴道干燥表达了担忧，能看出来她的妇科医生对讨论这两个问题感到不适。（“我想说，你不是阴道大夫吗？”她跟我说。“我用那玩意进行性生活的！”）

Their doctors’ responses prompted me to contemplate a thought experiment, one that is not exactly original but is nevertheless striking. Imagine that some significant portion of the male population started regularly waking in the middle of the night drenched in sweat, a problem that endured for several years. Imagine that those men stumbled to work, exhausted, their morale low, frequently tearing off their jackets or hoodies during meetings and excusing themselves to gulp for air by a window. Imagine that many of them suddenly found sex to be painful, that they were newly prone to urinary-tract infections, with their penises becoming dry and irritable, even showing signs of what their doctors called “atrophy.” Imagine that many of their doctors had received little to no training on how to manage these symptoms — and when the subject arose, sometimes reassured their patients that this process was natural, as if that should be consolation enough.

她们的医生的反应让我开始考虑进行一项思想实验，这项实验不怎么原创，却十分惊人。想象一下，男性人口的一大部分开始晚上走在街上，浑身汗津津的，而他们已经忍受这一问题好多年了。想象一下，这些男性走路跌跌撞撞地去上班，疲惫不堪，没精打采的，开会时总是一把脱下外套或帽衫，并且为了在能窗户边大口呼吸空气而离座。想象一下，这些男性中的许多人突然觉得性生活很痛苦，突然发现自己很容易尿路感染，阴茎变得干燥、易激，甚至会出现医生所说的“萎缩”。想象一下，他们中许多人的医生在如何应对相关症状方面鲜少、或根本没有接受过相关培训，并且当此类话题出现时，有时候医生还会让病人放宽心，称这一过程的出现很自然，仿佛这么说就足以给人慰藉。

Now imagine that there was a treatment for all these symptoms that doctors often overlooked. The scenario seems unlikely, and yet it’s a depressingly accurate picture of menopausal care for women. There is a treatment, hardly obscure, known as menopausal hormone therapy, that eases hot flashes and sleep disruption and possibly depression and aching joints. It decreases the risk of diabetes and protects against osteoporosis. It also helps prevent and treat menopausal genitourinary syndrome, a collection of symptoms, including urinary-tract infections and pain during sex, that affects nearly half of postmenopausal women.

现在，想象一下针对这些症状已经有了治疗方法，而医生往往没有留意。这一情境似乎不太可能出现，但对女性的更年期照护来说，这却是准确得令人沮丧的情况。确实是存在治疗方法的，而且并不难找，它被称为“更年期激素疗法”。该疗法能减轻潮热、睡眠紊乱的症状，并且可能减缓抑郁和关节疼痛。它能减少糖尿病的风险，让女性避免患上骨质疏松症。它还有助于预防和治疗更年期泌尿生殖系统综合征及一系列症状，包括尿路感染和性生活疼痛，这些症状影响着近半数绝经后女性。

Menopausal hormone therapy was once the most commonly prescribed treatment in the United States. In the late 1990s, some 15 million women a year were receiving a prescription for it. But in 2002, a single study, its design imperfect, found links between hormone therapy and elevated health risks for women of all ages. Panic set in; in one year, the number of prescriptions plummeted. Hormone therapy carries risks, to be sure, as do many medications that people take to relieve serious discomfort, but dozens of studies since 2002 have provided reassurance that for healthy women under 60 whose hot flashes are troubling them, the benefits of taking hormones outweigh the risks. The treatment’s reputation, however, has never fully recovered, and the consequences have been wide-reaching. It is painful to contemplate the sheer number of indignities unnecessarily endured over the past 20 years: the embarrassing flights to the bathroom, the loss of precious sleep, the promotions that seemed no longer in reach, the changing of all those drenched sheets in the early morning, the depression that fell like a dark curtain over so many women’s days.

更年期激素疗法在美国一度是医生最常采纳的疗法。在1990年代末，每年有约1500万女性会被开具这一处方。但在2002年，一项研究设计存在缺陷的研究发现激素疗法与各个年龄段女性健康风险升高存在关联。恐慌开始出现，在一年之间，该疗法的处方数量迅速下降。诚然，正如许多人们服用以减轻严重不适的药物一样，激素疗法是存在风险的，但自2002年以来，有数十个研究都提供了保证，即对60岁以下、受到潮热困扰的健康女性来说，服用激素药物的益处大于风险。然而，该疗法的名声不复从前，其后果也影响深远。光是想一想在过去20年里，那些没有必要经历忍受的、有损尊严的时刻有多少：令人丢脸地去卫生间的次数、宝贵的睡眠时间的损失、似乎再也无法得到的升职、晨间换下的那些被汗浸透的床单，以及在许多女性生活中，像黑色帘幕一般的抑郁症。

About 85 percent of women experience menopausal symptoms. Rebecca Thurston, a professor of psychiatry at the University of Pittsburgh who studies menopause, believes that, in general, menopausal women have been underserved — an oversight that she considers one of the great blind spots of medicine. “It suggests that we have a high cultural tolerance for women’s suffering,” Thurston says. “It’s not regarded as important.”

近85%女性会经历更年期症状。匹兹堡大学研究更年期的精神病学教授瑞贝卡·萨斯顿认为，更年期女性普遍都没有得到应有的治疗——她认为这一疏漏是医学最大的盲点之一。“这意味着我们对女性的受难在文化上有着极高的容忍度，”萨斯顿说。“被认为不重要。”

Even hormone therapy, the single best option that is available to women, has a history that reflects the medical culture’s challenges in keeping up with science; it also represents a lost opportunity to improve women’s lives.

即便是女性可用的最佳选择——激素疗法的历史，也反映出医学文化在跟上科学脚步方面面临的挑战。它还意味着错失了一个提升女性生活质量的机会。

“Every woman has the right — indeed the duty — to counteract the chemical castration that befalls her during her middle years,” the gynecologist Robert Wilson wrote in 1966. The U.S. Food and Drug Administration approved the first hormone-therapy drug in 1942, but Wilson’s blockbuster book, “Feminine Forever,” can be considered a kind of historical landmark — the start of a vexed relationship for women and hormone therapy. The book was bold for its time, in that it recognized sexual pleasure as a priority for women. But it also displayed a frank contempt for aging women’s bodies and pitched hormones in the service of men’s desires: Women on hormones would be “more generous” sexually and “easier to live with.” They would even be less likely to cheat. Within a decade of the book’s publication, Premarin — a mix of estrogens derived from the urine of pregnant horses — was the fifth-most-prescribed drug in the United States. (Decades later, it was revealed that Wilson received funding from the pharmaceutical company that sold Premarin.)

“每个女性都有权利——实际上是责任——去抵抗在她中年时期降临的化学阉割，”妇科医生罗伯特·威尔逊在1966年写道。1942年，美国食品药品监督管理局批准了首款激素治疗药物，但威尔逊的畅销书《青春永驻》(Feminine Forever)可被视为某种历史性里程碑——女性与激素治疗间问题重重的关系的开始。由于将性愉悦列为女性的优先事项，这本书在当时颇为大胆。但它也以为男性欲望服务的视角呈现出了对日益衰老的女性身体和不断下降的激素的直白鄙弃：服用激素药物的女性在性方面“更为大方”，并且容易“相处”。她们甚至更加不会出轨。在这本书出版不到十年，一种从怀孕母马尿液中提取出的结合性雌激素“普立马”成为了美国医生开药方数量排名第五的激素药。（几十年后，威尔逊被曝出收受了销售普立马的那家制药公司的资助。）

In 1975, alarming research halted the rise of the drug’s popularity. Menopausal women who took estrogen had a significantly increased risk of endometrial cancer. Prescriptions dropped, but researchers soon realized that they could all but eliminate the increased risk by prescribing progesterone, a hormone that inhibits the growth of cells in the uterus lining. The number of women taking hormones started rising once again, and continued rising over the next two decades, especially as increasing numbers of doctors came to believe that estrogen protected women from cardiovascular disease. Women’s heart health was known to be superior to men’s until they hit menopause, at which point their risk for cardiovascular disease quickly skyrocketed to meet that of age-matched men. In 1991, an observational study of 48,000 postmenopausal nurses found that those who took hormones had a 50 percent lower risk of heart disease than those who did not. The same year, an advisory committee suggested to the F.D.A. that “virtually all” menopausal women might be candidates for hormone therapy. “When I started out, I had a slide that said estrogen should be in the water,” recalls Hadine Joffe, a psychiatry professor at Harvard Medical School who studies menopause and mood disorders. “We thought it was like fluoride.”

1975年，令人担忧的研究结果抑制了这款药的普及。服用雌激素的更年期女性患子宫内膜癌的风险显著增加。医生对相关药的开方量下降，但研究人员迅速意识到，他们基本上可以通过开出孕激素来消除这种风险。孕激素是一种可以抑制子宫内膜细胞增长的激素。服用激素的女性人数再次开始增长，并且在接下来的20年持续增加，尤其是在这段时间里，有越来越多的医生认为孕激素有助于女性避免心血管疾病。更年期来临前，女性心脏健康普遍优于男性，而在之后，女性患心血管疾病的风险会迅速飙升至同年龄段男性的同等水平。1991年，一项针对4.8万绝经后护士的观察性研究发现，那些服用激素的女性患心脏病的风险比没有服用激素的女性低50%。同年，一个咨询委员会建议FDA将“几乎所有”更年期女性作为激素治疗适用对象。“我在刚入行的时候有一张幻灯片说应该往水里加雌激素，”哈佛医学院研究更年期和情绪障碍的精神病学教授哈丁·乔夫说。“我们当时觉得这就跟氟化物一样。”

Feminist perspectives on hormone therapy varied. Some perceived it as a way for women to control their own bodies; others saw it as an unnecessary medicalization of a natural process, a superfluous product designed to keep women sexually available and conventionally attractive. For many, the issue lay with its safety: Hormone therapy had already been aggressively marketed to women in the 1960s without sufficient research, and many women’s health advocates believed that history was repeating itself. The research supporting its health benefits came from observational studies, which meant that the subjects were not randomly assigned to the drug or a placebo. That made it difficult to know if healthier women were choosing hormones or if hormones were making women healthier. Women’s health advocates, with the support of the feminist congresswoman Patricia Schroeder, called on the National Institutes of Health to run long-term, randomized, controlled trials to determine, once and for all, whether hormones improved women’s cardiovascular health.

针对激素的女权主义观点则各不相同。一些人将其视为女性掌控自己身体的方式；另有人将其视为针对一个自然过程没有必要的医疗手段，认为这是意在让女性可以进行性生活、并保持传统意义上的吸引力的多余产品。对许多人来说，问题在于其安全性：激素疗法在1960年代就在没有经过充分研究的情况下被大肆推销给女性，并且许多女性健康倡导人士认为历史在重演。支持该疗法健康益处的研究属于观察性研究，这意味着研究对象并未被随机分配药物或安慰剂。这就很难明确到底是更为健康的女性在选择激素，还是激素让女性变得更加健康。在女权主义国会议员帕特丽夏·施罗德的支持下，女性健康倡导人士呼吁美国国家卫生研究院进行一项长期的随机对照试验，以一劳永逸地明确激素能否提升女性的心血管健康。

In 1991, Bernadine Healy, the first woman to serve as director of the N.I.H., started the Women’s Health Initiative, which remains the largest randomized clinical trial in history to involve only women, studying health outcomes for 160,000 postmenopausal women, some of them over the course of 15 years. Costs for just one aspect of its research, the hormone trial, would eventually run to $260 million. The hormone trial was expected to last about eight years, but in June 2002, word started spreading that one arm of the trial — in which women were given a combination of estrogen and progestin, a synthetic form of progesterone — had been stopped prematurely. Nanette Santoro, a reproductive endocrinologist who had high hopes for hormones’ benefit on heart health, told me she was so anxious to know why the study was halted that she could barely sleep. “I kept waking my husband up in the middle of the night to say, ‘What do you think?’” she recalled. Alas, her husband, an optometrist, could scarcely illuminate the situation.

1991年，国家卫生研究院首位女性院长伯纳丁·希利启动了妇女健康倡议(WHI)，这一研究至今仍是历史上仅以女性为对象的最大的随机对照临床试验。该试验对16万绝经女性的健康结果进行了研究，对其中一些对象的研究超过15年。该研究仅激素试验这一方面的花费最终就将达到2600万美元。激素试验当时预计将持续八年，但2002年6月，有传言说该试验的一个部分被提早叫停，其中包括女性得到雌激素和黄体制剂的组合治疗（黄体制剂为一种合成的孕激素）。曾对激素有益于心脏健康寄予厚望的生殖内分泌学家纳内特·桑托罗告诉我，她当时过于急于知道这项试验被叫停的原因，以至于几乎夜不能寐。“我总是在晚上把我丈夫弄醒，然后问他‘你怎么看？’”她回忆道。然而，作为一名验光师的丈夫基本没法给出什么有帮助的见解。

Santoro did not have to wait long. On July 9, the Women’s Health Initiative’s steering committee organized a major news conference in the ballroom of the National Press Club in Washington to announce both the halting of the study and its findings, a week before the results would be publicly available for doctors to read and interpret. Jaques Rossouw, an epidemiologist who was the acting director of the W.H.I., told the gathered press that the study had found both adverse effects and benefits of hormone therapy, but that “the adverse effects outweigh and outnumber the benefits.” The trial, Rossouw said, did not find that taking hormones protected women from heart disease, as many had hoped; on the contrary, it found that hormone therapy carried a small but statistically significant increased risk of cardiac events, strokes and clots — as well as an increased risk of breast cancer. He described the increased risk of breast cancer as “very small,” or more precisely: “less than a tenth of 1 percent per year” for an individual woman.

桑托罗无需等待太久。7月9日，WHI的指导委员会在华盛顿的全国新闻记者俱乐部召开了一场大型新闻发布会，以宣布这场研究被叫停的原因及其发现，这是在相关研究结果被公开、可以为医生阅读和解读的一周之前。WHI的代理主任、流行病学家杰奎斯·罗索乌告诉齐聚一堂的媒体，这项研究既发现了激素疗法的不良作用，也发现了其益处，但表示“不良作用大于益处，不良作用的数量也更多”。罗索乌说，这场试验没有像许多人希望的那样，发现服用激素可以防止女性患上心脏病，反而发现激素疗法对导致心血管事件、中风和血栓的风险出现幅度不大但具有统计学意义的增加——还会增加乳腺癌风险。他将乳腺癌风险描述为“非常小”，更准确说是对一位女性来说“每年不到千分之一”。

What happened next was an exercise in poor communication that would have profound repercussions for decades to come. Over the next several weeks, researchers and news anchors presented the data in a way that caused panic. On the “Today” show, Ann Curry interviewed Sylvia Wassertheil-Smoller, an epidemiologist who was one of the chief investigators for the W.H.I. “What made it ethically impossible to continue the study?” Curry asked her. Wassertheil-Smoller responded, “Well, in the interest of safety, we found there was an excess risk of breast cancer.” Curry rattled off some startling numbers: “And to be very specific here, you actually found that heart disease, the risk increased by 29 percent. The risks of strokes increased by 41 percent. It doubled the risk of blood clots. Invasive breast cancer risk increased by 26 percent.”

之后发生的是对未来数十年都造成了严重影响的一场误会。在接下来的几周里，研究人员和新闻主播向大众展示该数据的方式引发了一阵恐慌。在《今日秀》上，安·柯莉采访了流行病学家西尔维娅·瓦瑟泰尔-斯穆尔，她当时是WHI的首席研究员之一。“是什么让这场研究在伦理上无法进行下去？”柯莉问她。瓦瑟泰尔-斯穆尔回道，“安全起见，我们发现存在乳腺癌的过多风险。”柯莉快速说出一串令人震惊的数字：“非常确切地说，你们实际上发现心脏病的风险增加了29%。中风风险增加41%。血栓风险增加一倍。浸润性乳腺癌风险增加了26%。”

All of those statistics were accurate, but for a lay audience, they were difficult to interpret and inevitably sounded more alarming than was appropriate. The increase in the risk of breast cancer, for example, could also be presented this way: A woman’s risk of having breast cancer between the ages of 50 and 60 is around 2.33 percent. Increasing that risk by 26 percent would mean elevating it to 2.94 percent. (Smoking, by contrast, increases cancer risk by 2,600 percent.) Another way to think about it is that for every 10,000 women who take hormones, an additional eight will develop breast cancer. Avrum Bluming, a co-author of the 2018 book “Estrogen Matters,” emphasized the importance of putting that risk and others in context. “There is a reported risk of pulmonary embolism among postmenopausal women taking estrogen,” Bluming says. “But what is ‘risk’? The risk of embolism is similar to the risk of being on oral contraceptives or being pregnant.”

这些数字是准确的，但对于非专业观众来说难以解读，并且无可避免地听起来比实际情况更严重。例如，乳腺癌风险的增加也可以这样呈现：一名50-60岁女性患乳腺癌的风险约为2.33%。增加26%意味着该数字最终是2.94%。（而吸烟则会使患癌风险增加2600%。）另一种看待方式是每一万名服用激素的女性中，多出了八例患上乳腺癌的情况。2018年出版的书籍《雌激素很重要》(Estrogen Matters)的共同作者阿夫鲁姆·布鲁明强调了将上述风险和其他风险放入上下文的重要性。“服用雌激素中的女性存在报告肺栓塞风险的情况，”布鲁明说。“但什么才是‘风险’呢？栓塞的风险与服用口服避孕药和怀孕的风险差不多。”

The study itself was designed with what would come to be seen as a major flaw. W.H.I. researchers wanted to be able to measure health outcomes — how many women ended up having strokes, heart attacks or cancer — but those ailments may not show up until women are in their 70s or 80s. The study was scheduled to run for only 8½ years. So they weighted the participants toward women who were already 60 or older. That choice meant that women in their 50s, who tended to be healthier and have more menopausal symptoms, were underrepresented in the study. At the news conference, Rossouw started out by saying that the findings had “broad applicability,” emphasizing that the trial found no difference in risk by age. It would be years before researchers appreciated just how wrong that was.

这项研究设计本身后来被视为存在着缺陷。WHI的研究人员希望能衡量健康结果——有多少女性最终出现中风、心脏病和癌症，但这些疾病可能直到女性年届七八十岁才会出现。这项研究计划仅持续8.5年，所以他们考察的对象偏向于那些已经60岁或以上的女性。这一选择意味着那些更为健康、有着更多更年期症状的50多岁女性在这项研究中没有得到充分代表。在新闻发布会上，罗索乌一上来就说这些研究发现“可广泛适用”，强调称这项研究没有发现不同年龄段的风险有不同。多年之后，研究人员才意识到这个表述错得离谱。

The “Today” segment was just one of several media moments that triggered an onslaught of panicked phone calls from women to their doctors. Mary Jane Minkin, a practicing OB-GYN and a clinical professor at Yale School of Medicine, told me she was apoplectic with frustration; she couldn’t reassure her patients, if reassurance was even in order (she came to think it was), because the findings were not yet publicly available. “I remember where I was when John Kennedy was shot,” Minkin says. “I remember where I was on 9/11. And I remember where I was when the W.H.I. findings came out. I got more calls that day than I’ve ever gotten before or since in my life.” She believes she spoke to at least 50 patients on the day of the “Today” interview, but she also knows that countless other patients did not bother to call, simply quitting their hormone therapy overnight.

有许多媒体时刻触发了一大波恐慌的女性打给她们的医生，《今日秀》的那一段只是其中之一。执业妇产科医生、耶鲁医学院临床学教授玛丽·珍·米金告诉我，她当时都气炸了，由于研究结果还未向公众公开，她无法向她的病人们做出保证——如果还需要保证的话（她认为是需要的）。“我还记得当约翰·肯尼迪中枪时我在哪，”米金说。“我还记得9·11发生时我在哪。我也记得当WHI研究结果出来时我在哪。那天接的电话比我这辈子接到过的都多。”据她说，她那天和至少50位病人聊了《今日秀》的采访，但她也知道，还有无数的病人没有打电话，而只是在一夜之间就停止了激素治疗。

Within six months, insurance claims for hormone therapy had dropped by 30 percent, and by 2009, they were down by more than 70 percent. JoAnn Manson, chief of the division of preventive medicine at Brigham and Women’s Hospital and one of the chief investigators in the study, described the fallout as “the most dramatic sea change in clinical medicine that I have ever seen.” Newsweek characterized the response as “near panic.” The message that took hold then, and has persisted ever since, was a warped understanding of the research that became a cudgel of a warning: Hormone therapy is dangerous for women.

在六个月内，针对激素疗法的保险索赔就下降了30%，到2009年已经下降超过70%。布莱根妇女医院预防医学部主任、该研究首席研究人员之一乔安·曼森将其后果描述为“我见过的临床医学最天翻地覆的变化”。《新闻周刊》称其造成的反应“近乎恐慌”。当时盛行并且持续至今的信息是对该研究的一种曲解，并且成为了一个警告：激素疗法对女性很危险。

The full picture of hormone therapy is now known to be far more nuanced and reassuring. When patients tell Stephanie Faubion, the director of the Mayo Clinic Center for Women’s Health, that they’ve heard that hormones are dangerous, she has a fairly consistent response. “I sigh,” Faubion told me. She knows she has some serious clarifying to do.

人们现在知道，激素疗法从整体上看远不是那么黑白分明，并且不需要有太多顾虑。当患者告诉梅奥诊所女性健康中心主任斯蒂芬妮·福比恩，他们听说激素很危险时，她的反应总是一样的。“我会叹口气，”福比恩告诉我。她知道她要做出一些严肃的澄清。

Faubion, who is also the medical director of the North American Menopause Society (NAMS), an association of menopause specialists, says the first question patients usually ask her is about breast-cancer risk. She explains that in the W.H.I. trial, women who were given a combination of estrogen and progestin saw an increased risk emerge only after five years on hormones — and even after 20 years, the mortality rate of women who took those hormones was no higher than that of the control group. (Some researchers have hope that new formulations of hormone therapy will lessen the risk of breast cancer. One major observational study published last year suggested so, but that research is not conclusive.)

福比恩也是北美更年期协会(NAMS)的医学主任，这是一个由更年期问题专家组成的协会。她说患者通常问她的第一个问题是关于乳腺癌风险的。她解释说，在WHI试验中，服用雌激素和孕激素组合的女性仅在服用这些激素五年后才会发现风险增加，即使在20年后，服用这些激素的女性的死亡率也并不高于对照组。（一些研究人员希望激素疗法的新配方能够降低患乳腺癌的风险。去年发表的一项重要的观察性研究显示是这样，但研究并没有给出结论。）

The biggest takeaway from the last two decades of research is that age matters: For women who go through early menopause, before age 45, hormone therapy is recommended because they’re at greater risk for osteoporosis if they don’t receive hormones up until the typical age of menopause. For healthy women in their 50s, life-threatening events like clots or stroke are rare, and so the increased risks from hormone therapy are also quite low. When Manson, along with Rossouw, did a reanalysis of the W.H.I. findings, she found that women under 60 in the trial had no elevated risk of heart disease.

过去20年研究的最重要结论是年龄很重要：对于45岁之前经历过早期更年期症状的女性，建议进行激素治疗，因为如果她们不接受激素治疗、直到通常的绝经年龄的话，她们患骨质疏松症的风险会更大。对于50多岁的健康女性来说，血栓或中风等危及生命的情况很少见，因此激素治疗增加的风险也相当小。曼森在与罗索乌一起重新分析WHI的研究结果时发现，参与试验的60岁以下女性患心脏病的风险并未升高。

The findings, however, did reveal greater risks for women who start hormone therapy after age 60. Manson’s analyses found that women had a small elevated risk of coronary heart disease if they started taking hormones after age 60 and a significant elevated risk if they started after age 70. It was possible, researchers have hypothesized, that hormones may be most effective within a certain window, perpetuating the well-being of systems that are still healthy but accelerating damage in those already in decline. (No research has yet followed women who start in their 50s and stay on continuously into their 60s.)

然而，研究结果确实表明，60岁以后开始进行激素治疗的女性面临更大的风险。曼森的分析发现，如果女性在60岁之后开始服用激素，患冠心病的风险会小幅升高，70岁之后才开始服用，风险会显着升高。研究人员推测，激素可能在某个时间范围内最有效，可以使仍然健康的系统保持良好状态，但在已经处于衰退的系统中损害会加速。（目前还没有研究跟踪那些从50多岁开始接受激素治疗，一直持续到60多岁的女性。）

Researchers also now have a better appreciation of the benefits of hormone therapy. Even at the time that the W.H.I. findings were released, the data showed at least one clear improvement resulting from hormone therapy: Women had 24 percent fewer fractures. Since then, other positive results have emerged. The incidence of diabetes, for instance, was found to be 20 percent lower in women who took hormones, compared with those who took a placebo. In the W.H.I. trial, women who had hysterectomies — 30 percent of American women by age 60 — were given estrogen alone because they did not need progesterone to protect them from endometrial cancer, and that group had lower rates of breast cancer than the placebo group. “Nonetheless,” Bluming and his co-author, Carol Tavris, write in “Estrogen Matters,” “we have yet to see an N.I.H. press conference convened to reassure women of the benefits of estrogen.” Anything short of that, they argue, allows misrepresentations and fears to persist.

研究人员现在也对激素疗法的好处有了更多认识。即使在WHI结果刚公布的时候，数据也显示激素疗法至少带来了一项明显的改善：女性骨折的情况减少了24%。此后又发现了其他肯定性的结果。例如，研究发现，与服用安慰剂的女性相比，服用激素的女性糖尿病发病率降低了20%。在WHI试验中，接受过子宫切除术的女性（在美国60岁的女性中占比30%）只接受雌激素治疗，因为她们不需要黄体酮来保护她们免受子宫内膜癌的侵害，这组患者患乳腺癌的风险低于安慰剂组。“尽管如此，”布鲁明和他的合著者卡罗尔·塔夫里斯在《雌激素很重要》一书中写道，“我们还没有看到NIH召开新闻发布会，让女性相信雌激素的好处。”他们认为，如果不这样做，就会导致虚假陈述和恐惧持续存在。

Positive reports about hormone therapy for women in their 50s started emerging as early as 2003, and they have never really slowed. But the revelations have come in a trickle, with no one story gaining the kind of exposure or momentum of the W.H.I. news conference. In 2016, Manson tried to rectify the problem in an article for The New England Journal of Medicine, issuing a clear course correction of the W.H.I. findings as they pertained to women in their 40s and 50s. Since she published that paper, she feels, attitudes have changed, but too slowly. Manson frequently speaks to the press, and as the years passed — and more data accumulated that suggested the risks were not as alarming as they were first presented — you can almost track her increasing frustration in her public comments. “Women who would be appropriate candidates are being denied hormone therapy for the treatment of their symptoms,” she told me in a recent interview. She was dismayed that some doctors were not offering relief to women in their 50s on the basis of a study whose average subject age was 63 — and in which the risk assessments were largely driven by women in their 70s. “We’re talking about literally tens of thousands of clinicians who are reluctant to prescribe hormones.”

关于50多岁的女性接受激素疗法的正面报道早在2003年就开始出现，而且几乎一直没停过。但这些正面的揭示是一点一点出现的，没有一篇报道获得了WHI新闻发布会那样的曝光度或声势。2016年，曼森试图在《新英格兰医学杂志》的一篇文章中纠正这个问题，对WHI涉及40岁和50岁女性的研究结果进行明确的修正。她认为，自她发表那篇论文以来，人们的态度已经发生了变化，但转变速度太慢了。曼森经常对媒体发声，随着时间的推移——以及越来越多的数据表明这些风险并不像最初提出的那样令人担忧——你几乎可以在她的公开评论中察觉到她日益增加的挫败感。“本应适合接受激素疗法的女性正在被拒绝采用这一疗法来治疗她们的症状。”她在最近的一次采访中告诉我。让她感到沮丧的是，一些医生没有为50多岁的女性提供缓解措施，而他们的依据是一项受试者平均年龄为63岁的研究，而且其中存在风险的评估主要是由70多岁的女性带来的。“这里说的可是数以万计的临床医生，他们不愿意开激素处方。”

Even with new information, doctors still find themselves in a difficult position. If they rely on the W.H.I., they have the benefit of a gold-standard trial, but one that focused on mostly older women and relied on higher doses and different formulations of hormones from those most often prescribed today. New formulations more closely mimic the natural hormones in a woman’s body. There are also new methods of delivery: Taking hormones via transdermal patch, rather than a pill, allows the medication to bypass the liver, which seems to eliminate the risk of clots. But the studies supporting the safety of newer options are observational; they have not been studied in long-term, randomized, controlled trials.

即使有了新的信息，医生们仍然发现自己处于两难境地。如果他们以WHI研究为依据，那就是在倚仗一项金标准试验的优越性，但该试验主要针对的是老年女性，并且和今天最常用的激素处方比起来，它使用了更高的剂量，配方也不同。新配方更贴近女性体内的天然激素。还有新的给药方法：通过皮肤贴剂而非药丸服用激素可以让药物绕过肝脏，这似乎消除了血栓的风险。但支持新疗法安全性的研究只是观察性的，尚未对其进行长期、随机、对照试验的研究。

The NAMS guidelines emphasize that doctors should make hormone-therapy recommendations based on the personal health history and risk factors of each patient. Many women under 60, or within 10 years of menopause, already have increased baseline risks for chronic disease, because they are already trying to manage their obesity, hypertension, diabetes or high cholesterol. Even so, Faubion says that “there are few women who have absolute contraindications,” meaning that for them, hormones would be off the table. At highest risk from hormone use are women who have already had a heart attack, breast cancer or a stroke or a blood clot, or women with a cluster of significant health problems. “For everyone else,” Faubion says, “the decision has to do with the severity of symptoms as well as personal preferences and level of risk tolerance.”

NAMS指南强调，医生应根据每位患者的个人健康史和危险因素提出激素治疗建议。许多60岁以下或绝经10年内的女性患慢性病的基本风险本已增加，因为她们已经在努力控制肥胖、高血压、糖尿病或高胆固醇。即便如此，福比恩表示，“极少数女性存在绝对禁忌症”——这意味着对她们来说使用激素是不可能的。使用激素的风险最高的是已经有过心脏病发作、乳腺癌、或有过中风或血栓的女性，或者存在一系列严重健康问题的女性。“对于其他人来说，”福比恩说，“如何抉择取决于症状的严重程度以及个人偏好和风险承受能力。”

For high-risk women, other sources of relief exist: The selective serotonin reuptake inhibitor paroxetine is approved for the relief of hot flashes, although it is not as effective as hormone therapy. Cognitive-behavioral therapy has also been shown to help women with how much hot flashes bother them. Doctors who treat menopause are waiting for the F.D.A.’s review of a drug up for approval this month: a nonhormonal drug that would target the complex of neurons thought to be involved in triggering hot flashes.

对于高危女性来说，还有其他缓解方法：选择性血清素再摄取抑制剂帕罗西汀被批准用于缓解潮热，尽管它不如激素疗法那样有效。认知行为疗法也被证明可以帮助女性缓解潮热困扰。治疗更年期症状的医生正在等待FDA对本月提交的一种药物进行审批：这是一种针对被认为与引发潮热有关的神经元复合体的非激素药物。

Conversations about the risks and benefits of these various treatments often require more time than the usual 15-minute slot that health insurance will typically reimburse for a routine medical visit. “If I weren’t my own chair, I would be called to task for not doing stuff that would make more money, like delivering babies and I.V.F.,” says Santoro, now the department chair of obstetrics and gynecology at the University of Colorado School of Medicine, who frequently takes on complex cases of menopausal women. “Family medicine generally doesn’t want to deal with this, because who wants to have a 45-minute-long conversation with somebody about the risks and benefits of hormone therapy? Because it’s nuanced and complicated.” Some of those conversations entail explaining that hormones are not a cure-all. “When women come in and tell me they’re taking hormones for anti-aging or general prevention, or because they have some vague sense it’ll return them to their premenopausal self — and they’re not even having hot flashes — I say, ‘Hormone therapy is not a fountain of youth and shouldn’t be used for that purpose,’” Faubion says.

医保对一次常规就诊的报销时限通常是15分钟，然而关于各种疗法的风险和益处的商谈，往往用这点时间是不够的。“如果我不在这个位置，我也会因为没有去做能赚更多钱的事而受到责备，比如接生和试管婴儿，”现任科罗拉多大学医学院妇产科系主任的桑托罗说。她经常处理更年期女性的复杂病例。“家庭医生通常不想处理这个问题，谁愿意与某人就激素治疗的风险和益处进行45分钟的对话呢？因为那是很微妙而且复杂的。”其中一些对话需要解释激素并不是包治百病的灵丹妙药。“当女性进来告诉我她们正在服用激素来抗衰老或进行一般性预防，或者因为她们有某种模糊的认知，认为这会让她们恢复到绝经前的状态——而且她们甚至没有潮热时——我会说：“激素疗法不是青春之泉，不应该用于此目的，”福比恩说。

Too many doctors are not equipped to parse these intricate pros and cons, even if they wanted to. Medical schools, in response to the W.H.I., were quick to abandon menopausal education. “There was no treatment considered safe and effective, so they decided there was nothing to teach,” says Minkin, the Yale OB-GYN. About half of all practicing gynecologists are under 50, which means that they started their residencies after the publication of the W.H.I. trial and might never have received meaningful education about menopause. “When my younger partners see patients with menopausal symptoms, they refer them to me,” says Audrey Buxbaum, a 60-year-old gynecologist with a practice in New York. Buxbaum, like many doctors over 50, prescribed menopausal hormone therapy before the W.H.I. and never stopped.

太多的医生即便愿意，也无力去分析这些复杂的利弊。在WHI的研究发布后，医学院很快就放弃了与更年期相关的教育。“没有任何治疗方法被认为是安全有效的，所以他们认为没有什么可教的，”耶鲁大学妇产科医生米金说。大约一半的执业妇科医生年龄不到50岁，这意味着她们是在WHI的试验结果发布后开始住院医师实习的，可能从未在更年期方面接受过像样的教育。“比我年纪小的合作伙伴遇到有更年期症状的患者会转给我，”60岁的纽约执业妇科医生奥黛丽·布克斯鲍姆说。与许多50岁以上的医生一样，布克斯鲍姆在WHI试验之前就为患者开出过更年期激素疗法的处方，并且一直在这样做。

Education on a stage of life that affects half the world’s population is still wildly overlooked at medical schools. A 2017 survey sent to residents across the country found that 20 percent of them had not heard a single lecture on the subject of menopause, and a third of the respondents said they would not prescribe hormone therapy to a symptomatic woman, even if she had no clear medical conditions that would elevate the risk of doing so. “I was quizzing my daughter a few years ago when she was studying for the board exams, and whoever writes the board questions, the answer is never, ‘Give them hormones,’” Santoro says. In recent years, there has been some progress: The University of Pennsylvania has established a menopause clinic, and Johns Hopkins now offers classroom instruction and hands-on experience for its residents. But the field of gynecology will, most likely for decades to come, be populated by many doctors who left medical school unprepared to offer guidance to menopausal women who need their help.

影响着世界半数人口的一个人生阶段的教育在医学院仍然被严重忽视。2017年对全国住院医生进行的一项调查发现，20%的人没有上过任何关于更年期主题的课程，三分之一的受访者表示，他们不会对有症状的女性采用激素疗法，即使患者没有明确会增加这样做的风险的身体状况。“几年前，当我女儿正在准备医护资格考试时，我问了她这个问题，无论出题的人是谁，答案都不会是‘给她们激素’，”桑托罗说。近年来，事情获得了一些进展：宾夕法尼亚大学建立了更年期诊所，约翰·霍普金斯大学现在为学生提供课堂教学和实践机会。但在妇科领域仍然会有许多人从医学院毕业时没有这方面的准备，无法向需要帮助的更年期女性给出建议，这一点未来几十年恐怕都不会改变。

I didn’t know all of this when I went to see my gynecologist. I knew only what my friends had told me, and that hormone therapy was an option. The meeting was only my second with this gynecologist, a woman who struck me as chic, professional and in a bit of a hurry, which was to be expected, as she is part of a large health care group — the kind that makes you think you’d rather die from whatever’s ailing you than try to navigate its phone tree one more time. Something about the quick pace of the meeting — the not-so-frequent eye contact — made me hesitate before bringing up my concerns: They felt whiny, even inappropriate. But I forged on. I was having hot flashes, I told her — not constantly, but enough that it was bothering me. I had other concerns, but since memory issues were troubling me the most, I brought that up next. “But that could also just be normal aging,” she said. She paused and fixed a doubtful gaze in my direction. “We only prescribe hormones for significant symptoms,” she told me. I felt rebuffed, startled by how quickly the conversation seemed to have ended, and I was second-guessing myself. Were my symptoms, after all, “significant”? By whose definition?

我去看妇科医生时完全不知道这些。我只知道朋友们告诉我的那些，以及激素疗法是一种选择。那是我第二次与那位妇科医生会面，她给我的印象是时髦、专业、有些匆忙——这并不令人意外，因为她隶属于一家大型医疗集团，那种让人觉得宁愿死于任何让你不舒服的东西、也不愿拨打他们的自动应答电话的公司。我们的会面节奏很快，没有频繁的眼神交流，这让我在提出自己的担忧前犹豫不决：我觉得自己在发牢骚，甚至是不合时宜。但我还是坚持了下来。我告诉她，我有潮热，虽然不是经常性的，但已经足够让我感到困扰。而在所有问题中记忆问题是最困扰我的，所以我接着提出了这个问题。“但这也可能只是正常的衰老，”她说。她停顿了一下，略带怀疑地看了我一眼。“我们只针对明显的症状开激素处方。”她告诉我。我感到被拒绝了，谈话看起来如此之快就结束了也令我很吃惊。我开始怀疑自己。我的症状算“明显”吗？根据什么来定义呢？

The NAMS guidelines suggest that the benefits of hormone therapy outweigh the risks for women under 60 who have “bothersome” hot flashes and no contraindications. When I left my doctor’s office (without a prescription), I spent a lot of time thinking about whether my symptoms were troubling me enough to take on any additional risk, no matter how small. On the one hand, I was at a healthy weight and active, at relatively low risk for cardiovascular disease; on the other hand, because of family history and other factors, I was at higher risk for breast cancer than many of my same-age peers. I felt caught between the promises and, yes, risks of hormone therapy, the remaining gaps in our knowledge and my own aversion, common if illogical, to embarking on a new and indefinitely lasting medical regimen.

NAMS的指导方针指出，对于60岁以下、有“令人烦恼”的潮热且无禁忌症的女性来说，激素疗法的益处大于风险。离开医生办公室（没有获得处方）后，我花了很多时间思考我的症状是否足以让我承担任何额外的风险，无论风险有多小。一方面，我的体重很健康，也还有活力，罹患心血管疾病的风险相对较低；另一方面，由于家族病史和其他因素，我罹患乳腺癌的风险比许多同龄人都要高。我觉得自己被夹在了激素疗法的承诺和风险、我们的知识中仍然存在的空白以及我自己对开始一种新的、无限期持续的医疗方案的厌恶之间，这种厌恶虽说不合逻辑，但却是常见的。

Menopause could represent a time when women feel maximum control of our bodies, free at last from the risk of being forced to carry an unwanted pregnancy. And yet for many women, menopause becomes a new struggle to control our bodies, not because of legislation or religion but because of a lack of knowledge on our part, and also on the part of our doctors. Menopause presents not just a new stage of life but also a state of confusion. At a time when we have the right to feel seasoned, women are thrust into the role of newbie, or worse, medical detective, in charge of solving our own problems.

女性本应在更年期感觉到对自己的身体有了最大的控制权，我们至少终于可以摆脱被迫意外怀孕的风险了。然而，对许多女性来说，更年期成为了一场新的控制我们身体的斗争，这不是因为立法或宗教，而是因为我们和医生都缺乏相关知识。更年期不仅是人生的一个新阶段，也是一种困惑的状态。在我们有权感到自己经验丰富的时候，女性却被迫成为了一个新手，更糟的是还要承担起一个医学侦探的角色，负责解决我们自己的问题。

Even the most resourceful women I know, the kind of people you call when you desperately need something done fast and well, described themselves as “baffled” by this stage of their lives. A recent national poll found that 35 percent of menopausal women reported that they had experienced four or more symptoms, but only 44 percent said they had discussed their symptoms with a doctor. Women often feel awkward initiating those conversations, and they may not even identify their symptoms as menopausal. “Menopause has the worst P.R. campaign in the history of the universe, because it’s not just hot flashes and night sweats,” says Rachel Rubin, a sexual-health expert and assistant clinical professor in urology at Georgetown University. “How many times do I get a 56-year-old woman who comes to me, who says, Oh, yeah, I don’t have hot flashes and night sweats, but I have depression and osteoporosis and low libido and pain with sex? These can all be menopausal symptoms.” In an ideal world, Rubin says, more gynecologists, internists and urologists would run through a list of hormonal symptoms with their middle-aged patients rather than waiting to see if those women have the knowledge and wherewithal to bring them up on their own.

即使是我认识的最为聪慧的那些女性——当你急需又快又好地完成某件事情时你会打电话给她们的那种人——也说自己对人生的这一阶段感到“困惑”。最近的一项全国性调查发现，35%的更年期女性表示她们出现过四种或四种以上的症状，但只有44%的人表示她们曾与医生讨论过自己的症状。更年期女性在主动与医生谈及这些时往往会感到尴尬，她们甚至可能不认为自己的症状是更年期症状。“关于更年期的公关宣传是全宇宙历史上最糟糕的，因为它不仅仅是潮热和盗汗，”乔治敦大学性健康专家兼泌尿科临床助理教授蕾切尔·鲁宾说，“一位56岁的女性来找我，说‘哦，是的，我没有潮热和盗汗，但我有抑郁症和骨质疏松症、性欲低下而且在性生活中感到疼痛。这样的情况发生过多少次了？这些都可能是更年期症状。”鲁宾说，在一个理想的世界里，更多的妇科医生、内科医生和泌尿科医生会与他们的中年病人一起拿着荷尔蒙症状列表逐项讨论，而不是等着看这些女性是否有知识和能力自己提出这些症状。

The W.H.I. trial measured the most severe, life-threatening outcomes: breast cancer, heart disease, stroke and clots, among others. But for a woman who is steadily losing hair, who has joint pain, who suddenly realizes her very smell has changed (and not for the better) or who is depressed or exhausted — for many of those women, the net benefits of taking hormones, of experiencing an improved quality of life day to day, may be worth facing down whatever incremental risks hormone therapy entails, even after age 60. Even for women like me, whose symptoms are not as drastic but whose risks are low, hormones can make sense. “I’m not saying every woman needs hormones,” Rubin says, “but I’m a big believer in your body, your choice.”

WHI试验评估了最严重的、威胁生命的结果：乳腺癌、心脏病、中风和血栓等。但是，对于那些持续脱发、关节疼痛、突然发现自己的体味发生了变化（而且不是向好的方面变化）、抑郁或感到疲惫的女性来说，服用激素的净益处和日常生活质量的提高可能值得她们面对激素治疗带来的任何风险，即使她们已经过了60岁。即使对于像我这样症状不明显但风险较低的女性来说，服用激素也是有意义的。“我并不是说每个女性都需要激素，”鲁宾说，“但我坚信这是你自己的身体，你自己的选择。”

Conversations about menopause lack, among so many other things, the language to help us make these choices. Some women sail blissfully into motherhood, but there is a term for the extreme anxiety and depression that other women endure following delivery: postpartum depression. Some women menstruate every month without major upheaval; others experience mood changes that disrupt their daily functioning, suffering what we call premenstrual syndrome (PMS), or in more serious cases, premenstrual dysphoric disorder. A significant portion of women suffer no symptoms whatsoever as they sail into menopause. Others suffer near-systemic breakdowns, with brain fog, recurring hot flashes and exhaustion. Others feel different enough to know they don’t like what they feel, but they are hardly incapacitated. Menopause — that baggy term — is too big, too overdetermined, generating a confusion that makes it especially hard to talk about.

关于更年期的讨论缺乏很多东西，其中之一是在帮助我们做选择时所使用的语言。有些女性在成为母亲的过程中事事顺心，但也有一些女性分娩后忍受着极度的焦虑和抑郁，这就是产后抑郁症。有些女性每个月都会来月经，不会出现大的波动；有些女性则会出现情绪变化，扰乱日常工作，患上我们所说的经前综合征(PMS)，严重的还会患上经前焦虑症。有相当一部分女性在进入更年期时没有任何症状。一些人则遭受了近乎全身性的崩溃，出现脑雾、反复潮热和疲惫。还有一些人能够感受到自己身上发生的变化，并且清楚地知道自己不喜欢这样，但她们并非失去了行为能力。更年期这个宽泛的术语过于庞大，要素过于繁多，造成了一种混乱，让谈论它变得尤其困难。

No symptom is more closely associated with menopause than the hot flash, a phenomenon that’s often reduced to a comedic trope — the middle-aged woman furiously waving a fan at her face and throwing ice cubes down her shirt. Seventy to 80 percent of women have hot flashes, yet they are nearly as mysterious to researchers as they are to the women experiencing them — a reflection of just how much we still have to learn about the biology of menopause. Scientists are now trying to figure out whether hot flashes are merely a symptom or whether they trigger other changes in the body.

与更年期最密切相关的症状莫过于潮热，这种现象常常被简化为一种喜剧套路——中年妇女疯狂地对着脸扇扇子，往衣服里塞冰块。70%到80%的女性都会有潮热现象，但研究人员几乎和经历潮热的女性一样对它知之甚少。这反映出我们对更年期生物学还有多少需要了解的地方。科学家们现在正试图弄清，潮热仅仅是一种症状还是会引发身体的其他变化。

Strangely, the searing heat a woman feels roaring within is not reflected in any significant rise in her core body temperature. Hot flashes originate in the hypothalamus, an area of the brain rich in estrogen receptors that is both crucial in the reproductive cycle and also functions as a thermostat. Deprived of estrogen, its thermostat now wonky, the hypothalamus is more likely to misread small increases in core body temperature as too hot, triggering a rush of sweat and widespread dilation of the blood vessels in an attempt to cool the body. This also drives up the temperature on the skin. Some women experience these misfirings once a day, others 10 or more, with each one lasting anywhere from seconds to five minutes. On average, women experience them for seven to 10 years.

奇怪的是，女性体内灼热的感觉并没有反映在核心体温的明显升高上。潮热源于下丘脑，这是大脑中一个富含雌激素受体的区域，在生殖周期中起着至关重要的作用，同时也起着恒温器的作用。由于缺乏雌激素，下丘脑的恒温器现在变得不正常，它更容易将核心体温的微小升高误认为是太热了，从而引发大量出汗和血管广泛扩张，试图给身体降温。这也会使皮肤温度升高。有些女性一天会出现一次这种情况，有些则会出现10次或更多次，每次持续几秒钟到五分钟不等。女性经历这些症状的时间为七到10年。

What hot flashes might mean for a woman’s health is one of the main questions that Rebecca Thurston, the director of the Women’s Biobehavioral Health Laboratory at the University of Pittsburgh, has been trying to answer. Thurston helped lead a study that followed a diverse cohort of 3,000 women over 22 years and found that about 25 percent of them were what she called superflashers: Their hot flashes started long before their periods became irregular, and the women continued to experience them for as many as 14 years, upending the idea that, for most women, hot flashes are an irritating but short-lived inconvenience. Of the five racial and ethnic groups Thurston studied, Black women were found to experience the most hot flashes, to experience them as the most bothersome and to endure them the longest. In addition to race, low socioeconomic status was associated with the duration of women’s hot flashes, suggesting that the conditions of life, even years later, can affect a body’s management of menopause. Women who experienced childhood abuse were 70 percent more likely to report night sweats and hot flashes.

潮热对女性健康意味着什么，是匹兹堡大学妇女行为健康实验室主任丽贝卡·瑟斯顿一直试图回答的主要问题之一。瑟斯顿参与主持的一项研究对3000名女性进行了长达22年的跟踪调查，发现其中约25%的人是她所说的“超级潮热患者”，她们的潮热早在月经变得不规律之前就已经开始了，最长的持续了14年之久，这颠覆了大多数女性认为潮热只是一种恼人但短暂的不便的观点。在瑟斯顿研究的五个种族和民族群体中，发现黑人女性有潮热的最多，症状最令人烦恼，忍受潮热的时间也最长。除种族外，低社会经济地位也与女性潮热持续时间有关，这表明生活条件会影响人体对更年期的管理，即使这种影响在多年后才会体现出来。童年遭受虐待的女性报告盗汗和潮热的可能性要高出70%。

Might those symptoms also signal harm beyond the impact on a woman’s quality of life? In 2016, Thurston published a study in the journal Stroke showing that women who had more hot flashes — at least four a day — tended to have more signs of cardiovascular disease. The link was even stronger than the association between cardiovascular risk and obesity, or cardiovascular risk and high blood pressure. “We don’t know if it’s causal,” Thurston cautions, “or in which direction. We need more research.” There might even be some women for whom the hot flashes do accelerate physical harm and others not, Thurston told me. At a minimum, she says, reports of severe and frequent hot flashes should cue doctors to look more closely at a woman’s cardiac health.

除了对女性生活质量的影响之外，这些症状是否也预示着危害？2016年，瑟斯顿在学术期刊《中风》(Stroke)上发表的一项研究表明，潮热次数较多（每天至少四次）的女性往往有更多心血管疾病的迹象。这种联系甚至强于心血管风险与肥胖或高血压之间的联系。“我们不知道这是否是因果关系，”瑟斯顿告诫说，“也不知道是向哪个方向发展。我们需要更多的研究。”瑟斯顿告诉我，甚至可能有些女性会因为潮热而加快身体的衰老，有些则不会。她说，至少，关于严重和频繁潮热的报告应该提醒医生更密切地关注女性的心脏健康。

As Thurston was trying to determine the effects of hot flashes on vascular health, Pauline Maki, a professor of psychiatry at the University of Illinois at Chicago, was establishing associations between hot flashes and mild cognitive changes during menopause. Maki had already found a clear correlation between the number of a woman’s hot flashes and her memory performance. Maki and Thurston wondered if they would be able to detect some physical representation of that association in the brain. They embarked on research, published last October, that found a strong correlation between the number of hot flashes a woman has during sleep and signs of damage to the tiny vessels of the brain. At a lab in Pittsburgh, which has one of the most powerful M.R.I. machines in the world, Thurston showed me an image of a brain with tiny lesions represented as white dots, ghostlike absences on the scan. Both their number and placement, she said, were different in women with high numbers of hot flashes. But whether the hot flashes were causing the damage or the changes in the cerebral vessels were causing the hot flashes, she could not say.

瑟斯顿试图确定潮热对血管健康的影响，伊利诺伊大学芝加哥分校的精神病学教授宝琳·马基则正在建立潮热与更年期轻微认知变化之间的联系。马基已经发现，女性潮热的次数与记忆力之间存在明显的相关性。马基和瑟斯顿想知道，他们是否能在大脑中检测到这种关联的某种物理表现。他们着手进行的研究发现，女性在睡眠中潮热的次数与脑部微小血管受损的迹象之间存在很强的相关性。在匹兹堡的一个实验室里，瑟斯顿向我展示了一幅大脑图像，图像上的微小病变表现为白点，像幽灵一样消失在扫描仪上。她说，这些病变的数量和位置在潮热次数多的女性中都有所不同。但究竟是潮热导致了损害，还是脑血管的变化导致了潮热，她也无法确定。

About 20 percent of women experience cognitive decline during perimenopause and in the first years after menopause, mostly in the realm of verbal learning, the acquisition and synthesis of new information. But the mechanisms of that decline are varied. As estrogen levels drop, the region of the brain associated with verbal learning is thought to recruit others to support its functioning. It’s possible that this period of transition, when the brain is forming new pathways, accounts for the cognitive dip that some women experience. For most of them, it’s short-lived, a temporary neurological confusion. A woman’s gray matter — the cells that process information — also seems to shrink in volume before stabilizing in most women, according to Lisa Mosconi, an associate professor of neurology at Weill Cornell Medicine and director of its Women’s Brain Initiative. She compares the process the brain undergoes during those years of transition to a kind of “remodeling.” But the tiny brain lesions that Thurston and Maki detected don’t resolve — they remain, contributing incrementally, over many years, to an increased risk of cognitive decline and dementia.

约20%的女性在围绝经期和更年期的最初几年会出现认知能力下降，主要是在语言学习、获取和总结新信息方面。但这种下降的机制是多种多样的。随着雌激素水平下降，同语言学习相关的大脑区域被认为会招募其他区域来支持其运作。在这段过渡时期，大脑正在形成新的通路，这或许可以解释一些女性所经历的认知能力下降。对她们中的大多数人来说，这只是短暂的神经混乱。威尔康奈尔医学院神经学副教授兼女性大脑研究中心主任丽莎·莫斯科尼表示，大多数女性的灰质（处理信息的细胞）体积在稳定之前似乎也会缩小。她把大脑在这些过渡时期经历的过程比作一种“重塑”。但是，瑟斯顿和马基检测到的微小脑损伤并没有消除，它们依然存在，在多年时间里逐渐增加了认知能力下降和失智症的风险。

In the past 15 years, four randomized, controlled trials found that taking estrogen had no effect on cognitive performance. But those four studies, Maki points out, did not look specifically at women with moderate to severe hot flashes. She believes that might be the key factor: Treat the hot flashes with estrogen, Maki theorizes, and researchers might see an improvement in cognitive health. In one small trial Maki conducted of about 36 women, all of whom had moderate to severe hot flashes, half of the group received a kind of anesthesia procedure that reduced their hot flashes, and the other half received a placebo treatment. She measured the cognitive function of both groups before the treatment and then three months after and found that as hot flashes improved, memory improved. The trial was small but “hypothesis generating,” she says.

过去15年中，有四项随机对照试验发现，服用雌激素对认知能力没有影响。但马基指出，这四项研究并没有专门针对中度到重度潮热的女性。她认为这可能是关键因素：马基推断，如果使用雌激素治疗潮热，研究人员可能会发现认知健康有所改善。在马基进行的一项小型试验中，约有36名女性都有中度至重度潮热，其中一半人接受了一种能减轻潮热的麻醉治疗，另一半人则接受了安慰剂治疗。她测量了两组人在治疗前和治疗后三个月的认知功能，发现随着潮热的改善，记忆力也得到了提高。她说，这项试验的规模很小，但它“带来了假设”。

Even adjusting for greater longevity in women, Alzheimer’s disease is more frequent in women than men, one of many brain-health discrepancies that have led researchers to wonder about the role that estrogen — and possibly hormone therapy — might play in the pathways of cognitive decline. But the research on hormone therapy and Alzheimer’s disease has proved inconclusive so far.

即使考虑到女性寿命更长的因素，阿尔茨海默病在女性中的发病率也高于男性，这是大脑健康方面的众多差异之一，研究人员因此开始思考雌激素（可能还有激素疗法）在认知能力衰退过程中可能扮演的角色。但迄今为止，有关荷尔蒙疗法和阿尔茨海默病的研究尚无定论。

Whatever research exists on hormones and the brain focuses on postmenopausal women, which means it’s impossible to know, for now, whether perimenopausal women could conceivably benefit from taking estrogen and progesterone during the temporary dip in their cognitive function. “There hasn’t been a single randomized trial of hormone therapy for women in perimenopause,” Maki says. “Egregious, right?”

关于荷尔蒙和大脑的现有研究都集中在更年期女性身上，这意味着目前还无法知道围绝经期女性在认知功能暂时下降期间是否可以从服用雌激素和孕激素中获益。“还没有一项针对围绝经期女性的激素疗法随机试验，”马基说，“这太糟糕了，对吧？”

What’s also unclear, Thurston says, is how the various phenomena of cognitive change during menopause — the temporary setbacks that resolve, the progress toward Alzheimer’s in women with high genetic risk and the onset of those markers of small-vessel brain disease — interact or reflect on one another. “We haven’t followed women long enough to know,” says Thurston, who believes that menopause care begins and ends with one crucial dictum: “We need more research.”

瑟斯顿说，同样还不清楚的是，更年期的各种认知变化现象——暂时性的倒退、高遗传风险女性的阿尔茨海默氏症发展，以及小血管脑部疾病标志物的出现——是如何相互作用或相互反映的。瑟斯顿说：“我们还没有对女性进行足够长时间的跟踪研究，因此还无从得知。”她认为，更年期保健的起点和终点都需要一句关键的名言：“我们需要更多的研究”。

In the information void, a vast menopausal-wellness industry has developed, flush with products that Faubion dismisses as mostly “lotions and potions.” But a new crop of companies has also come to market to provide F.D.A.-approved treatments, including hormone therapy. Midi Health offers virtual face-to-face access to menopause-trained doctors and nurse practitioners who can prescribe hormones that some insurances will cover; other sites, like Evernow and Alloy, sell prescriptions directly to the patient. (Maki serves on the medical advisory boards of both Midi and Alloy.)

在信息存在空白的情况下，一个庞大的更年期保健产业应运而生，产品琳琅满目，但福比恩认为这些产品大多只是 “洗剂和药液”。但市场上也出现了一批新的公司，提供经FDA批准的治疗，包括激素疗法。Midi Health提供虚拟的面对面服务，由经过更年期治疗培训的医生和执业护士开具激素处方，一些保险机构也会承保这些药物；Evernow和Alloy等网站直接向患者出售药物。（马基是Midi和Alloy的医学顾问委员会成员）。

On the Alloy website, a woman answers a series of questions about her symptoms, family and medical history, and the company’s algorithm recommends a prescription (or doesn’t). A prescribing doctor reviews the case and answers questions by text or phone, and if the woman decides to complete the order, she has access to that prescribing doctor by text for as long as the prescription is active.

在Alloy网站上，女性回答一系列有关其症状、家庭和病史的问题，公司的算法就会推荐（或不推荐）处方。开处方的医生会审查病例，并通过短信或电话回答问题，如果女性决定完成订单，只要处方有效，她就可以通过短信与开处方的医生联系。

Alloy holds online support groups where women, clearly of varying socioeconomic backgrounds, often vent — about how hard it was for them to find relief, how much they are still suffering or how traumatized they still are by the lack of compassion and concern they encountered when seeking help for distressing symptoms. On one call in July, a middle-aged woman described severe vaginal dryness. “When I was walking or trying just to exercise, I would be in such agony,” she said. “It’s painful just to move.” She was trying to buy vaginal estradiol cream, an extremely low-risk treatment for genitourinary syndrome; she said there was a shortage of it in her small town. Until she stumbled on Alloy, she’d been relying on antibacterial creams to soothe the pain she felt.

Alloy举办在线支持小组活动，明显来自不同社会经济背景的女性经常在小组中倾诉——她们如何艰难寻找解脱的方法，她们仍在忍受多么大的痛苦，在承受痛苦而寻求帮助时，他人的缺乏同情和关心如何让她们依然饱受创伤。7月，一位中年女性在电话中描述了严重的阴道干涩症状。“走路或者想锻炼的时候，我都会觉得非常痛苦，”她说。“光是动一动都很疼”。她试图购买雌二醇阴道乳膏，这是一种风险极低的药物，用来治疗泌尿生殖系统综合征；她说，她所在的小镇上，这种药品非常短缺。在偶然发现Alloy之前，她一直依靠抗菌药膏来缓解疼痛。

The space was clearly a no-judgment zone, a place where women could talk about how they personally felt about the risks and benefits of taking hormones. At one meeting, a woman said that she’d been on hormone therapy, which she said “changed my life” during perimenopause, but that she and her sisters both had worrying mammograms at the same time. Her sister was diagnosed with breast cancer and had her lymph nodes removed; the woman on the call was diagnosed with atypical hyperplasia, which is not cancer but is considered a precursor that puts a woman at high risk. The NAMS guidelines do not indicate that hormone therapy is contraindicated for a woman at high risk of breast cancer, leaving it up to the woman and her practitioner to decide. “My new OB-GYN and my cancer doc won’t put me on hormones,” the woman said. She bought them from Alloy instead. “So I’m kind of under the radar.”

这个空间显然是一个没有人来品头评足的地方，女人们可以在这里谈论她们对激素治疗风险收益的个人感受。在一次小组讨论中，一名女性说，她一直在接受激素治疗，这在围绝经期“改变了我的生活”，但她和她的姐妹们同期的乳房X光检查结果让她们感到担忧。她的一位姐妹被诊断为乳腺癌，并切除了淋巴结；而她被诊断为非典型增生，虽然不是癌症，但被认为是一种使女性处于高风险之中的前兆。NAMS指南并没有表示激素疗法是乳腺癌高危女性的禁忌，而是让女人和她们的医生来决定是否接受这种疗法。这名女性说：“我新的妇科医生和癌症医生都不让我使用激素。”她转而从Alloy购买了激素。"所以，我现在有点偷偷摸摸的。”

No one at the meeting questioned the woman’s decision to go against the advice of two doctors. I mentioned the case to Faubion. “It sounds to me like she felt she wasn’t being heard by her doctors and had to go somewhere else,” she said. Faubion told me that in certain circumstances, higher-risk women who are fully informed of the risks but suffer terrible symptoms might reasonably make the decision to opt for hormones. But, she said, those decisions require nuanced, thoughtful conversations with health care professionals, and she wondered whether Alloy and other online providers were set up to allow for them. Anne Fulenwider, one of Alloy’s founders, said the patient in the support group had not disclosed her full medical history when seeking a prescription. After that came to light, an Alloy doctor reached out to her to have a more informed follow-up conversation about the risks and benefits of hormone therapy.

讨论会上没有人质疑这名女性违背两位医生建议的决定。我向福比恩提到了这个例子。她说：“在我看来，她觉得医生没有聆听她的想法，所以只好去别的地方求助。”福比恩告诉我，在某些情况下，充分了解风险但出现可怕症状的高风险女性可能会合理地做出选择激素疗法的决定。但她说，做这些决定需要与医护人员进行细致入微、深思熟虑的沟通，她不知道Alloy和其他在线服务提供商的机制是否能够做到。Alloy创始人之一安妮·福伦韦德说，支持小组中的一名病人在寻求处方时没有透露她的全部病史。在这一情况曝光后，Alloy的一名医生联系了她，就激素疗法的风险和益处进行了更加全面的后续咨询。

As I weighed my own options, I sometimes asked the doctors I interviewed outright for their advice. For women in perimenopause, who are still at risk of pregnancy, I learned, a low-dose birth control can “even things out,” suppressing key parts of the reproductive system and supplying a steadier dose of hormones. Another alternative is an intrauterine device (IUD) to provide birth control, along with a low-dose estrogen patch, which is less potent than even a low-dose birth-control pill and is therefore thought to be safer. “Too much equipment,” I told Rachel Rubin, the sexual-health expert, when she suggested it. “This is why I don’t ski.” I found myself thinking often about an insight that Santoro says she offers her patients (especially those under 60 and in good health): If you’re having any symptoms, how can you weigh the risks and benefits if you haven’t experienced the extent of the benefits?

在权衡我自己的选择时，我有时会直接向我采访过的医生寻求建议。我了解到，对于仍有怀孕风险的围绝经期妇女来说，低剂量避孕药物可以“平衡局面”，抑制生殖系统的关键部分，同时提供更稳定剂量的激素。另一种选择是使用宫内节育器(IUD)进行节育，同时使用低剂量雌激素贴片，这种贴片的药效甚至低于低剂量避孕药，因此被认为更安全。“装备太多了，”当性健康专家雷切尔·鲁宾建议我这么做的时候，我对她说。“所以我不滑雪。”然而我经常想起桑托罗说她给病人的忠告（尤其是60岁以下、身体健康的病人）：身体出现症状时，如果没有体验过治疗见效后的益处，你怎么能权衡这种疗法的风险和收益呢？

In November, I started on a low-dose birth-control pill. I am convinced — and those close to me are convinced — that my brain is more glitch-free. I have no hot flashes. Most surprising to me (and perhaps the main reason for that improvement in cognition): My sleep improved. I had not even mentioned my poor quality of sleep to my gynecologist, given the length of our discussion, but I had also assumed that it was a result of stress, age and a sweet but snoring husband. Only once I took the hormones did I appreciate that my regular 2 a.m. wakings, too, were most likely a symptom of perimenopause. The pill was an easy-enough experiment, but it carried a potentially higher risk of clots than the IUD and patch; now convinced that the effort of an IUD is worth it, I resolved to make that switch as soon as I could get an appointment.

11月，我开始服用低剂量避孕药。我和我身边的人都确信，我大脑的问题减少了。我没有潮热。最让我惊讶的是（也许这也是认知能力提高的主要原因）：我的睡眠改善了。鉴于我们讨论的时间太短，我甚至没有向我的妇科医生提到过我睡眠质量差的问题，但我也曾以为这是压力、年龄和一个体贴但打鼾的丈夫造成的。直到服用激素之后，我才意识到，我以前经常凌晨两点醒来，也很可能是围绝经期的症状。吃避孕药是个很简单的尝试，但它比宫内节育器和避孕贴有更高的潜在血栓风险；现在我确信使用宫内节育器是值得的，所以我决心一旦能够预约到时间，就立即改用这个方法。

How many women are doing some version of what I did, unsure of or explaining away menopausal symptoms, apologizing for complaining about discomforts they’re not sure are “significant,” quietly allowing the conversation to move on when they meet with their gynecologists or internists or family-care doctors? And yet … my more smoothly functioning brain goes round and round, wondering, worrying, waiting for more high-quality research. Maybe in the next decade, when my personal risks start escalating, we’ll know more; all I can hope is that it confirms the current trend toward research that reassures. The science is continuing. We wait for progress, and hope it is as inevitable as aging itself.

有多少女性和我曾经差不多一样，对更年期症状感到不确定或把它们轻描淡写，为抱怨自己不确定是否“严重”的不适而道歉，在与妇科医生、内科医生或家庭保健医生见面时默默地让话题换到下一个？然而……随着我的大脑运转得更加顺畅，我在思考、在担心、在等待更多高质量的研究。也许在下一个十年，当我的个人风险开始急剧升高，我们会懂得更多东西；我所能希望的是，它能证实目前的研究趋势，能让人放心。科学在前进。我们对进展翘首以待，盼着它像衰老本身一样必然到来。