睪酮素替代療法可改善慢性心臟衰竭男患者運動能力


  June 8, 2005 (聖地亞哥) - 在內分泌學協會的第87屆年會上有一項發表,根據一項為期12個月、雙盲性、安慰劑控制的臨床試驗結果顯示,中度至重度的慢性心臟衰竭(CHF)男性患者,可以藉由睪酮素替代療法來改善運動能力,並提升生活品質。
  
  主研究員之一的Hugh T. Jones醫師向Medscape表示,心臟衰竭關係到高度的死亡率,並會漸漸惡化,進而影響患者的外表與生活品質;我們之前曾經進行一項探測性的試驗,並將結果發表於2004年的心臟期刊中,男性在經過睪酮素治療後,身體的功能(FC)有著非常明顯的進步,在經過三個月的治療後,相較於安慰劑組,他們可以平均多行走65公尺。
  
  Jones醫師是英國Sheffield大學內分泌學術研究單位的內分泌顧問,也在Barnsley地區的綜合醫院擔任相同職務。
  
  在一追蹤研究中,研究人員隨機性的將76位(平均64歲)中度至重度CHF患者(紐約心臟協會,NHYA第2-4級,平均射出分率EF,32.5%(1.3%)分配至為期12個月的睪酮素替代試驗組(Androderm 5-mg貼片,Watson Laboratories公司製造),或安慰劑組;FC的改善以漸增式來回行走測試(ISWT)作評估。
  
  Jones醫師解釋,雖然睪酮素療法一般被視為慢性心臟衰竭患者的禁忌,但是之所以會有這項建議,是因為這些研究是將睪酮素以超過生理濃度的方式使用,如此會導致液體流動受阻;我們所做的是,將睪酮素的增加量控制在生理範圍內,平均的日增加量只有5.3 nmol (160 ng/dL),這樣的緩慢增量並不會引起水腫。
  
  研究結果顯示,相較於安慰劑,雖然睪酮素替代療法的最佳療效出現在第六個月(平均ISWT增加18%(7%,95% CI,4%~31%;平均步行距離增加38±13m,95% CI,11.6 ~ 64m)),效果卻呈現於整個12個月的試驗期中。
  
  另外,在試驗期裡,睪酮素治療的患者中,有35%至少改善了一級的NYHA等級,而安慰劑組的患者只有8%有此效果。
  
  Jones醫師指出,運動能力的改善顯見於睪酮素治療組,而安慰劑組卻有惡化的現象;三分之一的患者在NYHA等級上獲得改善,並沒有很多心臟衰竭的藥物可以做到這一點。
  
  第二級的結果顯示,睪酮素治療的患者維持了他們左心室的內腔長度,而安慰劑組卻有萎縮的現象(差異,-8.4±0.28mm);心室的大小,部分縮短的現象,或射出分率都沒有改變;Jones醫師指出,安慰劑組的患者,心臟的長度不但縮短,而且呈現球狀,這是心臟衰竭惡化的警訊。
  
  睪酮素的效果也包含了血管收縮壓的維持(差異,-6±6 mmHg),以及一般的肌肉功能,這個項目以手部握力的強度作測量。
  
  Jones指出,一般而言,睪酮素治療的患者可以維持它們的心臟及肌肉的狀態,安慰劑組則有惡化的現象;睪酮素治療可以改善情緒及認知的功能,他們對自我有著較好的感覺,相較於治療前,他們可以作更多的事情。
  
  根據Jones所述,睪酮素可能有助於與慢性心臟衰竭有關的惡病質,這個症狀會使得患者失去體重及肌肉質量;睪酮素曾經被證實,可以改善AIDS相關的惡病質,而我們對慢性心臟衰竭男性患者所做的,是唯一可以顯示出平行效果的研究。
  
  皮膚反應是最常見的睪酮素相關副作用,但是這類副作用可以藉由新處方的睪酮素予以避免。
  
  並沒有發現液體滯留的水腫;腦部血液排鈉胜激素、腫瘤壞死因子、攝護腺特定抗原或血球容積等,皆無明顯改變。
  
  Jones醫師總結指出,患有慢性心臟衰竭的男性,特別是睪酮素過低者,可以藉由睪酮素替代療法獲益,並改善運動能力及生活品質;血壓可以獲得一段時間的維持,NYHA等級有獲得改善的潛力;以睪酮素作心臟衰竭的治療,整體的安全性尚且需要更多的研究始能證實。
  
  本研究的經費來自英國國家心臟研究基金會,試驗用藥物則由Watson Laboratories公司提供,該公司為緩釋型睪酮素經皮貼片的製造者(Androderm)。

Testosterone Replacement Impro

By Yael Waknine
Medscape Medical News

June 8, 2005 (San Diego) — Testosterone replacement therapy significantly improves exercise capacity and quality of life in men with moderate to severe chronic heart failure (CHF), according to the results of a 12-month, double-blind, placebo-controlled trial presented here at ENDO 2005, the 87th Annual Meeting of the Endocrine Society.

"Heart failure is associated with a high mortality rate and gradual deterioration that affects patients' outlook and quality of life," Hugh T. Jones, MD, colead investigator, told Medscape. "We previously did a pilot study that was published in Heart in 2004, in which men treated with testosterone showed very significant improvements in functional capacity [FC] — they were actually walking a mean 65 m further at three months compared with those who had received placebo.''

Dr. Jones is a consultant endocrinologist at the University of Sheffield's Academic Unit of Endocrinology and Barnsley District General Hospital in the U.K.

In a follow-up study, investigators randomized 76 men (mean age, 64 years) with moderate to severe CHF (New York Heart Association [NYHA] class 2 - 4; mean ejection fraction [EF], 32.5% ± 1.3%) to receive 12 months of testosterone replacement therapy (Androderm 5-mg patch, made by Watson Laboratories, Inc.) or placebo. Improvements in FC were assessed using the incremental shuttle walk test (ISWT).

Although testosterone therapy is generally contraindicated in patients with CHF, Dr. Jones explained that the recommendation is based on studies in which testosterone was administered to supraphysiological levels that caused fluid retention. "What we did was increase testosterone levels to within the physiological range — the average increase in testosterone was only 5.3 nmol (160 ng/dL), a small increase that did not cause edema."

Results showed that testosterone replacement therapy improved FC throughout the 12-month period, relative to placebo (P = .006), although the effect was most significant at six months (mean increase in ISWT, 18% ± 7%; 95% confidence interval [CI], 4% - 31%; mean increase in distance, +38 ± 13 m; 95% CI, 11.6 - 64 m).

In addition, 35% of patients treated with testosterone improved by at least one NYHA class for the study period, compared with 8% of those administered placebo (P = .01).

"Exercise capacity improved significantly in patients who were taking testosterone, but deteriorated in those who were receiving placebo. NYHA class also improved in one third of patients, and there are not many drugs for heart failure that do that," noted Dr. Jones.

Secondary findings showed that patients treated with testosterone also maintained left ventricular cavity length, which decreased in the placebo group (difference, -8.4 ± 0.28 mm; P < .0001); no other changes were observed in dimensions, fractional shortening, or EF. "In patients treated with placebo, the heart length deteriorated and became globular, which is a sign of worsening heart failure," Dr. Jones pointed out.

Testosterone therapy also resulted in maintenance of systolic blood pressure (difference, -6 ± 6 mm Hg; P = .01) and increased general muscle function as determined by dominant handgrip strength (P = .04).

"In general, patients treated with testosterone maintained their cardiac and general muscle state, whereas those who were treated with placebo experienced deterioration," said Dr. Jones, adding that testosterone therapy can also improve mood and cognitive function. "Patients who were treated with testosterone felt better about themselves and were able to do more than they had been capable of prior to therapy."

According to Dr. Jones, testosterone may also benefit patients with CHF-related cachexia who are losing weight and muscle mass. "Testosterone treatment has also been shown to help men with AIDS-related cachexia and ours is the only study of note to show a parallel benefit in men with CHF."

Skin reactions were the most frequently reported adverse events associated with testosterone patch therapy and may be avoided with use of more recently approved testosterone formulations.

There was no evidence of edema or fluid retention, and no significant changes were observed in serum brain naturetic peptide, tumor necrosis factor, prostate-specific antigen, or hematocrit levels.

"Men with CHF, especially those with low testosterone levels, may benefit from testosterone replacement therapy in improved exercise function and quality of life, maintenance of blood pressure for a period, and the potential for improved NYHA class," Dr. Jones concluded. "More studies are needed before the full safety of testosterone in heart failure can be established."

The study was supported by a grant from the National Heart Research Fund (U.K.), and the study medication was provided by Watson Laboratories, Inc., the maker of testosterone extended-release transdermal film (Androderm).

ENDO 2005: Abstract PI1-294. Presented June 4, 2005.

Reviewed by Gary D. Vogin, MD

    



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