男性衰老，雌激素分泌不足也是關鍵
2013年09月12日
這是許多中年男人的痛苦：他們開始有了大肚腩，開始減少健身器械的配重，而且不知為何，沒有了年輕時候的性慾。
一個已經明確的元兇是睾酮，因為隨着時間的流逝，男人產生
的雄性激素漸漸變少。但現在還出現了一個令人驚訝的新答案。醫生稱這個答案會為有關男性身體如何變老的研究注入新的活力。結果證明，雌激素，也就是女性荷
爾蒙，在男性身體中發揮的作用遠大於之前的想像，而且，與女性一樣，雌激素水平降低會導致男性腰圍增大。
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Nathan Weber for The New York Times本·艾弗森參與了一項針對20歲至50歲男性的研究。受試者志願讓睾酮停止分泌16周。科學家們正在跟年長的男性身上重複此項研究，以衡量他們的生命力。
賓夕法尼亞大學(University of
Pennsylvania)醫學教授彼得·J·斯奈德博士(Peter J.
Snyder)表示，雌激素對男性的作用的相關發現是「一個重大進展」。斯奈德博士正在主持一個新的大規模研究項目——針對65歲及以上男性的激素療法。
一直以來，睾酮不足幾乎被認為是導致中年男性出現常見身體不適癥狀的唯一原因。
此項研究涉及一些新領域，比如弄清楚每一種激素對男性的作用，以及不同的激素水平如何影響身體機能。根據《新英格蘭醫學期刊》(The New England Journal of Medicine)周三發表的一篇論文，雖然睾酮水平下降是造成中年男性肌肉萎縮的原因，但雌激素水平的降低管控着脂肪的堆積。該論文提供了迄今為止最具說服力的證據，證明雌激素是導致中年男性遇到麻煩的主要因素。這兩種激素都是激發性慾所需的。
周三，哈佛大學醫學院(Harvard Medical
School)內分泌學家、上述論文的第一作者喬爾·芬克爾斯坦博士(Joel
Finkelstein)在新聞通稿中表示，「通常被認為是因為睾酮不足而產生的一些癥狀，實際上部分或幾乎完全是由雌激素減少引發的。」
芬克爾斯坦博士的論文只是一系列研究的開端，在很多人看來，這些研究有望讓我們對男性身體中睾酮及雌激素的作用形成一種新的認識。斯奈德博士正在主持另一項名為「睾酮臨床試驗」(Testosterone
Trial)的研究。該研究測量兩種激素的水平，並探尋睾酮治療是否能使睾酮水平低的年長男性變得更年輕——使他們走得更快、感覺更有活力、增強性功能與
記憶力，並強化骨骼。小規模研究的結果讓人看到了希望，但並不可靠，而且雌激素還沒有成為考慮因素。
「我們以前忽略了男性身體中的雌激素，但我們現在正在做相
關研究，」華盛頓大學醫學院(Washington University School of
Medicine)睾酮及老年病學研究員、退伍軍人事務部皮吉特灣醫療系統(V.A. Puget Sound Health Care
System)研究員阿爾文·M·松本博士(Alvin M.
Matsumoto)說。「在這方面，我們只是剛剛起步。」松本博士是睾酮臨床試驗項目的研究員。
無論是男性還是女性，雌激素都是由睾酮轉化而來的。男性的
睾酮水平較高，因此他們最終的雌激素水平至少是絕經女性的兩倍多。由於隨着年齡的增長，兩種激素的水平都有所降低，身體會出現一些變化。但迄今為止，研究
人員幾乎只注重研究雌激素對女性的影響，以及睾酮對男性的影響。
芬克爾斯坦博士的研究為兩種激素各自的功能及其在不同水平
下的表現給出了一份新路線圖。結果表明，不同程度的睾酮缺乏會觸發不同的癥狀。他發現，睾酮是肌肉張力和去脂體重的首要調節因素，但維持肌肉所需的睾酮水
平比之前預想的要低。年輕男性的平均水平是每100毫升血清中含有550毫微克睾酮。醫生們普遍認為，低於300毫微克的話就屬於過低，可能需要治療，而
一般的治療藥物為睾酮凝膠。
然而，芬克爾斯坦博士的研究發現，除非睾酮水平降至200毫微克以下的極低水平，肌肉力量與尺寸不會受到影響。不過，脂肪堆積會在較高的水平發生：睾酮為300到350毫微克的時候，雌激素就會降至觸發中年發福的水平。
至於性慾與性表現，兩者均需要一定的雌激素和睾酮，而且隨着這兩種激素水平的上升而穩步提高。研究人員稱，現在距離給出諸多明確建議還差很遠，不過，並不建議男性使用雌激素，因為高劑量的雌激素會導致胸部增大等女性特徵的出現。
芬克爾斯坦博士表示，儘管醫生會為每100毫升血清中睾酮
含量低於300毫微克的男性開出睾酮凝膠的處方，但這種一刀切的標準過於武斷，而且沒有臨床依據。一般情況下，男性使用激素是為了治療疲勞、抑鬱或性慾減
退等癥狀，但它們與睾酮水平低下的關係並不明確。芬克爾斯坦博士稱，數據顯示，睾酮水平在300毫微克的男性如有性問題的話，可以嘗試使用睾酮，但肌肉乏
力的人則不應歸咎於睾酮不足。不過，他還說，「睾酮水平低下的癥狀往往非常不明顯。」
目前有數百萬男性使用睾酮凝膠，促成了一個近20億美元（約合122億元人民幣）的市場。
為了進行研究，芬克爾斯坦博士及同事招募了400名20到50歲的男性。他們志願讓睾酮停止分泌16周。其中一半接受不同劑量的外來睾酮，另外一半則同時使用一種藥物，讓雌激素停止合成。這樣，研究者可以分析在沒有雌激素的情況下睾酮的效應。
芬克爾斯坦博士目前正在更年長的男性身上重複這項實驗。斯奈德博士的睾酮臨床試驗也以年長男性為研究對象。
斯奈德博士及同事招募了近800名年齡不低於65歲的睾酮
水平低下男性。其中一組人用安慰劑，另一組人則用睾酮，使得血清含量達到400到800毫微克之間。研究人員正在測試他們的行走速度、性功能、活力、記憶
力、紅細胞計數、骨骼和冠狀動脈。這項研究為期一年，將於明年完成。
研究者稱，下一步，他們希望開展一項大型研究，和2002年的一次涉及數千名女性的激素療法長期風險與益處的研究類似。比如說，他們想知道，睾酮療法是否會提高前列腺癌風險？能否預防心肌梗塞？
「我們還不清楚這些臨床問題的答案，」松本博士說。「它到底能不能預防一些很重要的東西？」
翻譯：許欣、黃錚Middle-Aged Men Can Blame Estrogen for That Waistline, Too
September 12, 2013
It is the scourge of many a middle-aged man: he
starts getting a pot belly, using lighter weights at the gym and somehow
just doesn’t have the sexual desire of his younger years.
The obvious culprit is
testosterone, since men gradually make less of the male sex hormone as
years go by. But a surprising new answer is emerging, one that doctors
say could reinvigorate the study of how men’s bodies age. Estrogen, the
female sex hormone, turns out to play a much bigger role in men’s bodies
than previously thought, and falling levels contribute to their
expanding waistlines just as they do in women’s.
The discovery of the role of estrogen in men is “a
major advance,” said Dr. Peter J. Snyder, a professor of medicine at the
University of Pennsylvania, who is leading a big new research project
on hormone therapy for men 65 and over. Until recently, testosterone
deficiency was considered nearly the sole reason that men undergo the
familiar physical complaints of midlife.
The new frontier of
research involves figuring out which hormone does what in men, and how
body functions are affected at different hormone levels. While dwindling
testosterone levels are to blame for middle-aged men’s smaller muscles,
falling levels of estrogen regulate fat accumulation, according to a study published
Wednesday in The New England Journal of Medicine, which provided the
most conclusive evidence to date that estrogen is a major factor in male
midlife woes. And both hormones are needed for libido.
“Some of the symptoms
routinely attributed to testosterone deficiency are actually partially
or almost exclusively caused by the decline in estrogens,” said Dr. Joel
Finkelstein, an endocrinologist at Harvard Medical School and the
study’s lead author, in a news release on Wednesday.
His study is only the start
of what many hope will be a new understanding of testosterone and
estrogen in men. Dr. Snyder is leading another study, the Testosterone Trial,
which measures levels of both hormones and asks whether testosterone
treatment can make older men with low testosterone levels more youthful —
by letting them walk more quickly, feel more vigorous, improve their
sexual functioning and their memories, and strengthen their bones.
Smaller studies have been promising but unreliable, and estrogen has not
been factored in.
“We had ignored this
hormone in men, but we are studying it now,” said Dr. Alvin M.
Matsumoto, a testosterone and geriatrics researcher at the University of
Washington School of Medicine and the V.A. Puget Sound Health Care
System, who is a Testosterone Trial researcher. “We are just starting
out on this road.”
Both men and women make
estrogen out of testosterone, and men make so much that they end up with
at least twice as much estrogen as postmenopausal women. As levels of
both hormones decline with age, the body changes. But until now,
researchers have focused almost exclusively on how estrogen affects
women and how testosterone affects men.
Dr. Finkelstein’s study
provides a new road map of the function of each hormone and its behavior
at various levels. It suggests that different symptoms kick in at
different levels of testosterone deficiency. Testosterone, he found, is
the chief regulator of muscle tone and lean body mass, but it takes less
than was thought to maintain muscle. For a young man, 550 nanograms of
testosterone per deciliter of blood serum is the average level, and
doctors have generally considered levels below 300 nanograms so low they
might require treatment, typically with testosterone gels.
But Dr. Finkelstein’s study
found that muscle strength and size turn out to be unaffected until
testosterone levels drop very low, below 200 nanograms. Fat
accumulation, however, kicks in at higher testosterone levels: at 300 to
350 nanograms of testosterone, estrogen levels sink low enough that
middle-aged spread begins.
As for sexual desire and
performance, both require estrogen and testosterone, and they increase
steadily as those hormone levels rise. Researchers say it is too early
to make many specific recommendations, but no one is suggesting that men
take estrogen, because high doses cause feminine features like enlarged
breasts.
Although doctors prescribe
testosterone gels for men whose levels fall below 300 nanograms per
deciliter, that cutoff point is arbitrary, and there is no clinical
rationale for it, Dr. Finkelstein said. Often men take the hormone to
treat complaints like fatigue, depression or loss of sexual desire,
which may or may not be from low levels of testosterone. The data
suggest that men with levels around 300 nanograms who complain of sexual
problems may want to try testosterone, but those who complain of
flagging muscle strength should not blame testosterone deficiency, Dr.
Finkelstein said. But, he added, “symptoms of low testosterone tend to
be quite vague.”
Today, millions of men are using testosterone gels, fueling a nearly $2 billion market.
For their study, Dr.
Finkelstein and his colleagues recruited 400 men aged 20 to 50 who
agreed to have their testosterone production turned off for 16 weeks.
Half then received varying amounts of testosterone, while the other half
also got a drug that shuts off estrogen synthesis so the researchers
could assess the effects of having testosterone but not estrogen.
Now Dr. Finkelstein is repeating the study with older men. The Testosterone Trial is looking at them too.
For that study, Dr. Snyder
and his colleagues recruited nearly 800 men aged 65 and older who have
low testosterone levels. The men take either a placebo or enough
testosterone to bring their level to between 400 and 800. Investigators
are assessing walking speed, sexual functioning, vitality, memory,
red-blood-cell count, bones and coronary arteries. The yearlong study
will be completed next year.
Next, researchers said, they want to do a large study like one conducted with thousands of women
in 2002 that asked about long-term risks and benefits of hormone
therapy. Does testosterone therapy lead, for example, to more prostate
cancer? Does it prevent heart attacks?
“We still don’t know the
answers to the clinical questions,” Dr. Matsumoto said. “Does it prevent
things that are really important?”
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