남성갱년기치료의최신지견 / 김광민 2012 대한임상건강증진학회추계통합학술대회연수강좌 남성갱년기치료의최신지견 김광민아주대학교의과대학 내용 남성갱년기를치료해야하는이유 남성갱년기환자찾아내기 남성갱년기치료 남성갱년기를치료해야하는이유 낮은남성호르몬이높은사망률과관련 대사증후군과관

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1 남성갱년기치료의최신지견 / 김광민 연수강좌 남성갱년기치료의최신지견 김광민아주대학교의과대학 내용 남성갱년기를치료해야하는이유 남성갱년기환자찾아내기 남성갱년기치료 남성갱년기를치료해야하는이유 낮은남성호르몬이높은사망률과관련 대사증후군과관련 치료시대사증후군인자및당뇨병에서혈당개선효과 삶의질개선효과 남성호르몬저하가사망률증가와관련이있다 Men with low testosterone levels were found to have a 88% greater mortality risk due to all causes than men with normal testosterone levels 대사증후군 / 당뇨병이있는남성에서의 Testosterone 대사증후군인자의정도및혈중테스토스테론은역의상관관계 허리둘레와테스토스테론은역의상관관계 당뇨병과테스토스레론은역의상관관계 Survival times are shorter in men with low T Similar findings in the EPIC-Norfolk and Rancho Bernardo studies Shores MM et al. Arch Intern Med. 2006:166:

2 연수강좌 Testosterone in Men Suffering from the Metabolic Syndrome Epidemiological, longitudinal studies; low testosterone is an independent risk factor for the development of both the metabolic syndrome and type 2 diabetes in later life. Prevalence of metabolic syndrome according to sex hormone quartiles(korean data) Low testosterone is a risk factor for metabolic syndrome and diabetes in men who were not initially obese. --- MMAS Q1 Q2 Q3 Q4 Total testosterone * SHBG * Free testosterone Maturitas pub 예정 Summary for Effects of testosterone on Type 2 diabetes and components of Mets 남성갱년기의정의 Improvement in insulin resistance and HbA1c, coupled with reductions in visceral obesity and improvements in body composition in all studies. 노화과정과관련이있으며, 특징적인증상과혈중남성 호르몬결핍 ( 젊은건강한성인남성의참고치이하로 ) 으 로특징지워지는임상적, 생화학적증후군 Beneficial effects on lipids and blood pressure in some, but not all 삶의질에중대한변화를일으키며, 골, 지방조직, 근육, 조혈, 뇌, 피부등다중기관의기능에안좋은영향 2008 ISA, ISSAM, EAU, EAA and ASA recommendations Morales A & Lunenfeld B 2002, The Aging Male;5: 남성갱년기의발병률및유병률 연령에따라서증가 ; 흔한질환 Symptomatic androgen deficiency 발병률 ; % per 1000 person-years - 5.9%, 11.2%, 23.3% per 1000 person-years (40 대, 50 대, 60 대 ) 유병률 ; 5.6 % %, - 연령, 허리둘레, 자신이느끼는건강상태, 동반질환등에의해증가 J Clin Endocrinol Metab. 2004;89 Morley JE, Metabolism 1997; 46: Ferrini RL, Am J Epidemiol 1998;147: Harman SM, J Clin Endocrinol Metab 2001; 86: Andre B. Araujo,J Clin Endocrinol Metab 92: , 2007 남성호르몬저하 복잡하고다양한병인 낮은남성호로몬 : 스트레스, 노화, 질병, 그리고약물복용등과관계 많은임상질병 - 급성의심한질환 - 만성질환 : 당뇨병, 심혈관질환, 고혈압, hereditary hemochromatosis, HIV virus infection - 음주, 흡연등의생활습관 - 영양결핍혹은비만 116

남성갱년기치료의최신지견 / 김광민 Diagnosis and evaluation of patients with suspected androgen deficiency(i) Making a diagnosis of androgen deficiency only in men with consistent symptoms and signs and

3 남성갱년기치료의최신지견 / 김광민 Diagnosis and evaluation of patients with suspected androgen deficiency(i) Making a diagnosis of androgen deficiency only in men with consistent symptoms and signs and unequivocally low serum testosterone levels. TABLE 1. Symptoms and signs suggestive of androgen deficiency in men A. More specific symptoms and signs Incomplete or delayed sexual development, eunuchoidism Reduced sexual desire (libido) and activity Decreased spontaneous erections Breast discomfort, gynecomastia Loss of body (axillary and pubic) hair, reduced shaving Very small (especially <5 ml) or shrinking testes Inability to father children, low or zero sperm count Height loss, low trauma fracture, low bone mineral density Hot flushes, sweats B. Other less specific symptoms and signs Decreased energy, motivation, initiative, and self-confidence Feeling sad or blue, depressed mood, dysthymia Poor concentration and memory Sleep disturbance, increased sleepiness Mild anemia (normochromic, normocytic, in the female range) Reduced muscle bulk and strength Increased body fat, body mass index Diminished physical or work performance 남성갱년기의대표적임상증상 신체적특징의변화 복부비만 (Fat Mass 증가 & Lean body mass 감소 ) 근육량및근력감소 골밀도감소 체모감소및피부변화 기분의변화 의욕감소 ( 우울감 ) 기억력집중력감소 인지기능감소 피로감증가 성기능저하 성욕감퇴 발기력저하, 특히야간발기능저하 semen amount 감소 Note: Sexual symptoms may be absent TDS 진단 남성호르몬결핍을의미하는증상과징후 가장흔한증상 : 성욕저하 (?) 발기부전, 근육량감소및근력감소, 체지방증가, 골밀도감소및골다공증, 활력감소및우울감등 The changes of mean total testosterone levels during the follow-up intervals are described according to age tertiles (a), obesity (b), DM (c), and metabolic syndrome (d) 저성선증에특징적인증상, 징후는없으나, 증상, 징후가남성호르몬결핍의가능성을높힘. 낮은혈중남성호르몬과더불어하나이상의증상 Clinical Endocrinology (2012) 77, 어떤사람이잘생기나? 노화 생활습관 : 비만, 과도한음주, 스트레스 만성질환 : 고혈압, 심혈관질환, 당뇨, 만성폐쇄성폐질환등 남성갱년기진료지침 Testosterone Therapy in Men with Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline (2010) - J Clin Endocrinol Metab 95: , 2010 ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of lateonset hypogonadism in males (2008) - European Journal of Endocrinology (2008) 159:

4 연수강좌 권고와증거 (1) 초기진단검사 - 믿을만한검사방법에의하여아침총남성호르몬측정 혈중남성호르몬은아침에최고조에달하는일중변동 권고와증거 (2) 진단의확진 ; 총남성호르몬의반복측정이필요 초기남성호르몬수치가경도의저성선증범주에들었던남성의 30% 가반복측정에서정상남성호르몬수치 건강하고젊은남성의 15% 가일중 24 시간동안에정상범주이하로떨어지기도 한번의남성호르몬측정이개인의수준을특정화시키기에는불충분할정도로남성호르몬 Day-to-day variations 이충분히크게나타남 Assay-to-assay variability - liquid chromatography tandem mass spectrometry > immunoassay 권고와증거 (3) An approach for the diagnostic evaluation of adult men suspected of having androgen deficiency 총남성호르몬농도가정상범주의하한치가까이있으면서 SHBG 변이가있을것이라고의심되는사람에서, 정확하고신뢰있는방법을사용하여유리형혹은생이용가능한남성호르몬측정이필요 0.5-3% Free (unbound) 42% Weakly bound to albumin Bioavailable T 55% Bound with high affinity to SHBG (biologically inactive) Total T Bhasin, S. et al. J Clin Endocrinol Metab 2010;95: 남성호르몬결핍이라고판단되는경우추가평가 일차성저성선증과이차성저성선증을구별하기위한혈중 LH 와 FSH 측정권장 내용 남성갱년기를치료해야하는이유 이차성저성선증에서시상하부혹은뇌하수체기능부전의원인을찾기위한세밀한평가가필요 불명확원인에의한일차성저성선증에서, 특히정소의부피가 6 ml 이하인경우 Klinefelter 증후군을배제하기위하여 karyotype 평가가필요 남성갱년기환자찾아내기 남성갱년기치료 심한남성호르몬결핍혹은낮은손상골절이있는경우 DEXA 골밀도검사권장 118

5 남성갱년기치료의최신지견 / 김광민 남성호르몬보충요법시고려사항 남성호르몬보충요법에의해실제적으로호전이될수있는임상적증후군이어야 남성호르몬결핍을확진하는방법 남성호르몬제제의선택? 경구용, 주사용, 패취혹은겔제제 제제선택에따라서결과에서의미있는변화들이있는지여부 남성호르몬치료에의해환자를치료해야하는임상적증상들을실제적으로개선시킬수있는것인지 Treatment of androgen deficiency with testosterone (I) We recommend testosterone therapy for symptomatic men with classical androgen deficiency syndromes aimed at inducing and maintaining secondary sex characteristics and at improving their sexual function, sense of well-being, and bone mineral density. We suggest initiating testosterone therapy with any of the following regimens, chosen on the basis of the patient s preference, consideration of pharmacokinetics, treatment burden, and cost. TABLE 4. Conditions in which testosterone administration is associated with a high risk of adverse outcome and for which we recommend against using testosterone Very high risk of serious adverse outcomes Metastatic prostate cancer Breast cancer Moderate to high risk of adverse outcomes Unevaluated prostate nodule or induration PSA >4 ng/ml (>3 ng/ml in individuals at high risk for prostate cancer) Hematocrit >50% Severe lower urinary tract symptoms associated with benign prostatic hypertrophy as indicated by AUA/IPSS >19 Uncontrolled or poorly controlled congestive heart failure Untreated obstructive sleep apnea Monitoring of men receiving testosterone therapy 1. 치료에반응하는지, 부작용이나타나는지치료시작후 3 개월, 그리고일년마다환자를평가 2. 치료시작후 2-3 개월후남성호르몬검사 : 혈중남성호르몬이정상값의중간정도까지상승하는것이목표치 3. 치료시작시, 3 개월후그리고해마다 hematocrit 측정 4. 치료시작시, 3 개월후수지직장검사와 PSA 측정, 그리고그이후에는환자의연령, 인종에의존한전립선암선별지침에따라서진행 Summary (1) Testosterone is a key player in glucose homeostasis, lipid metabolism, and cardiovascular pathology Its deficiency leads to a serious deterioration of the health of men expressing itself in the metabolic syndrome and its sequels: diabetes mellitus type 2 and atherosclerotic disease accelerating morbidity and mortality Normalization of testosterone levels may improve insulin sensitivity and have favorable effects on visceral adiposity and lipid profiles J Clin Endocrinol Metab Jun;91(6):

6 연수강좌 Summary (2) 흔한질환으로연령, 증상및징후, 관련질환등을고려할경우진단가능성이높아짐 적극적으로찾아내고치료하려는노력이필요 120

07-임상건강-초록(안태영)

07-임상건강-초록(안태영) 소강당 연수강좌 : 남성갱년기클리닉 울산의대 남성건강 (Men s Health) 과연관된해부학적기관은전립선, 음경, 그리고고환이다. 그중에서고환에서생성되는테스토스테론이감소되어발현되는다양한남성갱년기증상을일컬어남성호르몬결핍증후군 (testosterone deficiency syndrome) 이라한다. 충분한영양섭취가가능해지고의료수준이향상되면서한국인의평균수명은 1999년