Human papillomavirus infection and cervical cancer

More than 50% of young women who have had sex early in life acquire cervical human papillomavirus (HPV) infection. Most of the infections are with the high-risk HPV types, which are potential ethiologic factor for cervical cancer. Although ten or more HPV types are thought to be of high-risk, perhaps less than 30% of such infections persist and less than 1.5% develop cancer. Many previous studies clarify the oncogenic potentials of HPV16 or 18 genes by the experimental transformation of cells, introduced with target genes. Some molecular events induced with E6 and E7 genes of high-risk HPV types could explain the mechanisms of HPV for promoting cancer development. One important step for the malignant progression by HPV is the stable expression of HPV E6 and E7 oncoproteins in the host cells, and this may be caused by the integration of the HPV genome into the host genome. The E6 and E7 proteins induce uncontrollable cell growth and accumulate mutations in the host genome after many cell divisions by inhibiting the functions of Rb and p53, which tightly regulate cell division cycle. However, it is postulated that such molecular events may occur only in cells able to escape from the immune-surveillance system, since all viral proteins are potentially immunogenic and targeted by the immune cells. Thus, immune responses to HPV and immune-evasion mechanisms of HPV play the most important role for persistent HPV infection and the progression of cervical diseases. It is reported that increased helper T type 2 (Th2) responses (suppression of cell-mediated immunity) and reduction of Th1 responses (no stimulation of cell-mediated immunity) are more frequently observed in cervical intraepithelial neoplasia (CIN) lesions than in normal cervices, suggesting that immune suppression is involved in CIN development. Correlations between certain major histocompatibility complex (MHC) class I and class II alleles and susceptibility to cervical carcinoma or protection against HPV infection are reported, suggesting that the genetic background related to immune responses may contribute to different outcome in the women who are infected with HPV. HPV appears to evade the host immune responses by several mechanisms: (i) avoidance of viral antigen recognition, (ii) induction of HPV 16 E7 tolerance, (iii) modulation of the signal transduction pathways of interferons and other cytokines such as interkeukin-18, and MHC antigens, (iv) inhibition of surrounding immune cell activity by secreted E6 and E7 proteins. Both immune-suppressive and oncogenic actions induced with HPV infection may allow HPV-infected cells to transform into cancer cells in vivo by conferring survival abilities against the growth inhibitory or apoptotic stimulation of cytokines and the attack of killer cells.Biomedical Reviews 2003; 14: 75-93

Complete Remission of Human Parvovirus B19 Associated Symptoms by Loxoprofen in Patients with Atopic Predispositions

Two cases of women in their thirties with past histories of atopic dermatitis and allergic rhinitis developed a low grade fever, followed by a butterfly-shaped erythema, swelling of their fingers, and polyarthralgia. Despite such symptoms that overlap with those of systemic lupus erythematosus (SLE), the diagnostic criteria for SLE were not fulfilled. Due to positive results for human parvovirus B19 (HPV-B19) IgM antibodies in the serum, diagnoses of HPV-B19 infection were made in both cases. Although acetaminophen failed to improve their deteriorating symptoms, a nonsteroidal anti-inflammatory drug (NSAID), loxoprofen, completely removed the symptoms immediately after the administration. In those cases, since the patients were predisposed to atopic disorders, an increased immunological response based on the lymphocyte hypersensitivity was likely to be involved in the pathogenesis. The immunomodulatory property of NSAID was thought to repress such lymphocyte activity and thus provided a rapid and sustained remission of the disease

HPV16 L1-E7キメラ粒子産生酵母を用いた予防・治療的ワクチン

高リスク型ヒトパピローマウイルス(HPV)のHPV16が子宮頚癌の発生を誘発することが明らかになっている。したがって、HPV16に対して有効な免疫を誘導することが感染防止や将来の癌発生防止に有効であると考えられている。米国のグループがHPV16型L1蛋白を酵母で発現させて作成したウイルス様粒子(VLP)をワクチンとして人に免疫したところ、100%その感染は抑えられたと報じられた。このワクチンは注射ワクチンで、精製したウイルス様粒子を計3回の注射を行っている。効果はみとめられたが、このワクチンは単価が高く、また、低開発国など医療設備が充実していない地域において、このワクチンの保存や注射そのものが難しいなどの問題点がある。そこで、安価で経口投与出来るワクチンの開発が期待されている。最近、我々はHPV16型様粒子を産生する酵母を経口投与した後にごく少量のVLPを鼻粘膜に投与することで、HPV16型特異的な抗体が誘導されることを発見した。本研究では、この研究を発展させ、HPV16型感染の防御のみならず、HPV16型特異的なキラーT細胞を誘導し、治療を目的としたワクチンの作成を試みた。S.pombeの発現ベクターにHPV16L1-E7(L1を短くしたC-末に全長のE7を導入したもの)を組み込んで発現させたところ、57kD,63kD,67kDの蛋白発現に成功した。このHPV16L1-E7を発現する酵母を凍結乾燥させ、マウスに食べさせたところ、HPV16様粒子(VLP)に反応することを確認した。このことから、この融合蛋白がL1だけで構成される粒子と同じような粒子を形成し、それによって抗体産生が誘導されることが示唆された。E7に対するキラーT細胞が誘導されているかどうかについて今後検討する予定であり、もしこれが誘導されれば、予防的かつ治療的ワクチンとして有望となる可能性がある。High-risk HPV, such as HPV type 16 was the most important etiologic factor for cervical cancer, which is the secondary many cancer in women worldwide. Therefore, HPV vaccine development is one of the best ways to reduce the incidence of cervical cancer, especially in manu developing countries Koutsky et al. first demonstrate that HPV16-L1 virus-like particles (VLP), which was produced from yeast can protect HPV16-infection in women who undertook parenteral vaccination of the VLP. This suggests that VLP vaccine is highly effective against HPV16 infection. However, the parenteral VLP vaccine may be not useful in many developing countries, since it is very expensive and the injection procedure may be difficult to perform in such countries where medical stuffs are limited. We have found that an edible freeze-dried yeast vaccine containing HPV16-L1 protein enhanced with intranasal administration of a suboptimal dose of HPV16-VLP is able to induce HPV16-specific antibody responses in mice mo del system. In the present study, we tried to make recombinant yeast expressing L1-E7 chimeric protein in order to synthesize VLP containing oncoprotein E7. We made three different-sized L1-E7 DNA constracts which contained full-length of E7 and truncated L1 genes, and transfected them into yeast, and had got three strains of yeast expressing 57kD, 63KD, and 67KD proteins, respectively. Since we succeeded to purify VLP from the yeast producing 63KD protein, we used this strain for an edible yeast vaccine in the mice model system. If the chimeric L1-E7 VLP induced antibody against HP16, and incorporated E7 protein induced cytotoxic T lymphocytes killing HPV16-infected cell, this vaccine might be useful as prophylactic and therapeutic vaccine against HPV16 infection. In the preliminary experiment, we found that this vaccine induces HPV16 L1 antibody in the immunized mice. Now we are going to investigate this further, and to test the cytotoxic T lymphocyte response to HPV16-E7 protein in the mice.研究課題/領域番号:15591735, 研究期間(年度):2003-2004出典：「HPV16 L1-E7キメラ粒子産生酵母を用いた予防・治療的ワクチン」研究成果報告書　課題番号15591735 (KAKEN：科学研究費助成事業データベース（国立情報学研究所）)　　　本文データは著者版報告書より作

子宮頚癌患者における抗ヒトパピローマウイルス(HPV)免疫回避機構

ほとんどの粘膜型HPVを検出できるLCR-E7PCR法を開発した。この方法により日本におけるHPV感染の頻度、癌発生に関与するタイプのHPVの感染パターンを明らかにした。子宮頚部細胞に変化を認めないHPVの感染初期(細胞診正常、コンジローマ、LSIL(Low-grade squamous intraepithelial lesions))の女性では、17種類以上のHPVが単独または混合感染しており、特に混合感染が高頻度にみられたが、HSIL(Hitgh-grade squamous intraepithelial neoplasia)や子宮頚癌では混合感染の頻度は減少し、単独感染として検出されることが多かった。HPV16,18,31,33,51,52,56,58はこれらの悪性病変で検出されたためハイリスク型と考えられる。日本の子宮頚癌では、欧米に比べてHPV18,33,56型は少なく、HPV51,52,58型が多い傾向を示した。HLA classII抗原型との相関を調べたところ、HLA DR3,4の女性はHPV感染が成立し易く,HLA DR2,3,4,5またはDR2-DQw1,DR3-DQw2,DR5-DQw3 haplotypeは子宮頚癌の発症と相関していた。またHPV16DNA陽性でHLA DR2,3,4,5の女性は、それ以外のHLAタイプ群に比べてHPV16ウイルス抗体価が上昇していた。これらのHLA型の女性では、HPV感染後にTh2HelperT細胞の活性化が有意となりB細胞を刺激して抗体産生が誘導されるが、逆にTh1 Helperは抑制されている可能性が示唆された。そこで、このことを証明するために、頚癌組織中のTh1型サイトカイン(IL2,γ-INF)、Th2型サイトカイン(IL4,IL5)の発現を免疫染色により検査したが、特徴的な変化は今のところ見いだせていない。We have recently established the system to detect DNA of most mucosal HPV types using PCR method, which is called LCR-E7 PCR method. Using this method, we tested the prevalence of HPV infection in clinical samples. More than 17 HPV types were identified in normal, condyloma and lower-grade squamous intraepithelial lesions (LSIL). Higher incidence of infection with multiple HPV types was observed in these benign lesions than in the malignant lesions such as high-grade squamous intraepithelial lesions (HSIL) and invasive cervical (ICCA). HPV 16, 18, 31, 33, 51, 52, 56, and 58 were detected as a single infection in HSIL and ICCA, suggesting these are high-risk types for cancer. HPV51, 52 and 58 were more prevalent, whereas HPV18, 33 and 56 were less prevalent in Japanese ICCA than that in the USA.We investigated an association between HLA class II types and susceptibility for cervical cancer or the high-risk HPV infection. Women with HLA DR3, 4 were more susceptible to the high-risk HPV infection, and women with HLA DR2, 3, 4, 5 or with DR2-DQw1, DR3-DQw2, DR5-DQw3 haplotypes were susceptible to cervical cancer. Interestingly, women with DR2, 3, 4, 5 showed higher titers of anti-HPV 16 antibodies that in women with the other HLA types. This suggests that up-regulation of Th2 type immuno-response inducing strong humoral immuno-response may occur in these women with DR2, 3, 4, 5. We surmised that those women may have weaker Th1 response that make susceptible to HPV infection and cervical cancer. Immunohistochemical analysis showed no specific expression patterns of both Th1 and Th2-related cytokines in some tissue samples of cervical cancer. It may be important to study much more samples for such cytokine responses to conduct certain conclusions.研究課題/領域番号:10671526, 研究期間(年度):1998-1999出典：「子宮頚癌患者における抗ヒトパピローマウイルス(HPV)免疫回避機構」研究成果報告書　課題番号10671526 (KAKEN：科学研究費助成事業データベース（国立情報学研究所）)　　　本文データは著者版報告書より作

腸管粘膜リンパ組織刺激によるヒトパピローマウイルス(HPV)ワクチン

HPV16感染は子宮頚癌を誘発する。したがって、HPV16の感染予防ワクチンの開発が進められている。HPV16などの癌誘発HPVに感染する若い女性のほとんど(70-90%)は自然治癒するという疫学結果があり、HPV感染予防ワクチンの臨床応用に際して、どのような対象者にHPVワクチンをするのかという問題点がある。HPV感染防御は、治療法のない現在において、女性の健康にとって重要な問題であるため、より簡便で低コストのワクチン開発が期待されている。最近、鼻粘膜にHPV16VLPを免疫することで有効な中和抗体が誘導されるることを明らかになった。本研究では、我々が開発したHPV16VLPを産生する酵母をマウスに食べさせ、食べるワクチンによって有効なHPV抗体が誘導されるかどうか検討した。方法は、2系統のマウス(Balb C, C57BL)を用い、酵母またはHPV6型酵母を食べさせたものを陰性コントロール、精製したHPV16VLPを鼻粘膜に処置したものを陽性コントロールとした。6匹はHPV16酵母のみ食べさせ、あとの12匹はHPV16酵母とコレラトキシン(CT)(アジュバント)を食べさせた。HPV抗体はHPV-VLPを抗原にしたELISA法で測定した。その結果、HPV16VLPに反応する血清中IgG抗体は、陰性コントロールは陰性であったが、2匹の陽性コントロール、HPV16酵母のみ処置したマウスの50%(3/6)、HPV16酵母+CTマウスの30%(4/12)に誘導された。陽性例の抗体力価は、陽性コントロールとHPV16酵母処置群との間に差はみられなかった。膣粘液中の粘液のIgA抗体はHPV16VLP+CTマウスの17%(2/12)にのみ誘導された。これらの抗体は、変性したcapsid抗原には反応しなかったことから、中和能を持つと考えられた。より有効な免疫法を樹立するため、現在、実験条件を変えて追加実験中である。Human papillomavirus type16 (HPV16) is the most important risk factor for cervical cancer. Thus, effective prophylactic vaccine against HPV 16 is expected for prevention of cervical cancer development, which is the secondary common cancer of women worldwide.Recent study showed that nasal administration of HPV16 virus-like particles (VLP) is able to elicit mucosal antibody neutralizing HPV 16. In the present study, we tested an efficacy of orally administered HPV16 vaccine using yeast synthesizing HPV 16 VLP (HPV 16 VLP-yeast). Preliminary experiments showed that freeze dried yeast was good candidate for delivering antigen to the gut and stimulating the gut-associated lymphoid tissues (GALT), since it was not digested in the stomach but digested in the intestine.Positive control mice were nasally administered with purified HPV16 VLP (Nasal-Ad), and the others were orally administered with freeze dried yeast (Oral-Ad). Two mice were orally administered with control yeast, two mice with HPV6 VLP-yeast, 6 mice with HPv16 VLP-yeast, and 12 mice with HPV16 VLP-yeast and Cholera toxin (CT). HPV-specific antibody responses were tested with HPV6- and 16-VLP-ELISA. Two Nasal-Ad mice, 3 of 6 Oral-Ad mice with HPV16 VLP-yeast, and 4 of 12 Oral-Ad mice with HPV 16 VLP-yeast + CT elicited HPV 16-specific IgA and IgG serum antibody (Ab), whereas mice administered with control yeast or with HPV6-VLP-yeast had no such responses.The liters of the serum Ab were as high as those in the mice nasally administered with HPV16 VLP, and no difference in serum Ab titers was observed by administrating CT or not. Weak but HPV 16-specifc IgA responses were detected in vaginal secretions of 2 of 12 Oral-Ad mice with CT. Now we are optimizing the condition able to induce stronger mucosal IgA response.研究課題/領域番号:13671701, 研究期間(年度):2001-2002出典：「腸管粘膜リンパ組織刺激によるヒトパピローマウイルス(HPV)ワクチン」研究成果報告書　課題番号13671701 (KAKEN：科学研究費助成事業データベース（国立情報学研究所）)　　　本文データは著者版報告書より作

子宮頚癌発生に関係するタイプのヒトパピローマウイルスに対する血清診断法の開発

金沢大学医学部附属病院HPV16型ウイルス様粒子を抗原としたELISA法により、HPV16型感染に特異的な抗体の検出法を開発した。子宮頚癌や高度異形成患者では有意に抗HPV16及びその類縁タイプの悪性型HPVに対するIgA IgG抗体が40%以上の患者で誘導されていることを証明した。またこれらの抗体の上昇、特に血清IgA抗体の上昇は、HPVの初期感染者および子宮頚癌や高度異形成などの進行病変をもつ患者にもみられるということを世界に先駆けて報告した。これらの抗体価の上昇は、悪性病変を持つ女性とHPV16型に持続的に感染している細胞診正常女性に顕著であり、これらの抗体価陽性化は頚癌への進行のバロメーターとなる可能性が示唆された。子宮頚癌発生予防のためのワクチンには、ウイルスの外殻を有するがウイルス遺伝子を有さないHPV-VLPが理想的と考えられている。欧米で始まろうとしているHPV-VLPワクチンのヒト臨床治験にさきがけて、HPV感染宿主や頚癌患者における液性免疫の誘導状態について把握することはことは、重要と考えられる。また、日本の北陸地方と中国東北部における大規模な疫学調査により、HPV16,18,31,52,58型などのHPV感染が子宮頚癌の最も重要な危険因子であることを再確認した。日本の女性における、子宮頚癌の危険因子の検討では、未婚、結婚後10-19年、3回以上の妊娠、分娩がHPV感染に従属した危険因子であるのに大して、喫煙はHPV感染に従属しない危険因子であることを疫学的に証明した。また欧米での血清疫学的報告とは異なり、Chlamydia trachomatis DNAの陽性率と頚癌発生との因果関係は見いだされなかった。Immunoglobulins A and G (IgA and IgG) responses against HPV 16 virus-like particles (VLP) were tested by ELISA in 100 women with cervical lesions, 26 atypical cells of undetermined significance (ASCUS) and 14 cytologically normal women with HPV DNA.As controls, 130 age-matched cytologically normal women with no HPV DNA were selected from the population in which the cases generated. The existence of HPV DNA in cervical samples were tested by PCR-based method. Normal women positive with HPV 16 DNA were followed up at 4-7 months intervals for 16-24 months. IgA and IgG antibodies against HPV 16-VLP were frequently detected in these women repeatedly positive for HPV16 DNA,suggesting that the persistent HPV infection is crucial for effective antibody responses against the viruses. IgA response appears earlier and persist longer that IgG response. Women with HPV DNA of types 16,31/33/35,58 and unknown types showed significantly higher seropostivity for both IgA and IgG antibodies than the controls (P<0.05 for both). No significant seropositivity for IgA nor IgG was detected in HPV 18/45-DNA positive group. HPV 31/33/35,58 appear to be close types to HPV 16, whereas HPV 18/45 to be distinct to HPV 16 in antigenicity. IgA and IgG responses against HPV 16-VLP were more frequently observed in women with normal cervices with HPV DNA,ASCUS,HSIL and cervical cancer than in the controls. High serological responses were dependent on HPV 16-infection in HSIL and cervical cancer cases, although the association between serological responses and HPV types were not apparent in the more beign changes such as ASCUS and LSIL.Antibody positive reflects persistent viral infection that may increase the risk for malignant progression of the cervix. Thus this serological assay using HPV 16-VLP may be useful as a new diagnostic tool supplementing cervical cytological tests.研究課題/領域番号:08671877, 研究期間(年度):1996 – 1997出典：研究課題「子宮頚癌発生に関係するタイプのヒトパピローマウイルスに対する血清診断法の開発」課題番号08671877（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-08671877/086718771997kenkyu_seika_hokoku_gaiyo/）を加工して作

子宮頚部における高リスク型ヒトパピローマウイルスE4蛋白の発現と免疫応答

ヒトパピローマウイルス(HPV)E4蛋白は、ウイルスの粒子の放出に重要な蛋白で上皮細胞内で大量に発現する。本研究では、HPV感染初期病変におけるE4蛋白の発現と免疫応答の関係を調査し、HPVに対する免疫の回避機構を明らかにすることが目的である。研究に先立ち、2006年度には、CIN患者の感染HPVタイプを明らかにするため、GP5+/6+PCR法に改良を加えて方法でHPV-DNA診断とsequence法によるタイプ判定を行った。その後、新しく市販されている3種類のHPV typing kitを用いた結果を比較検討したところ、検査法によりHPVタイプ結果が異なる場合があること、異なるHPVタイプの混合感染が予想以上に多いことを発見した。特に混合型感染例におけるHPVタイプ一致率が低い傾向がみられる。現在、これらの調査結果を解析し、各kit間の違いを明らかにしている段階である。HPV11,16,18,31,33,45,56型に対する抗E4抗体を英国の共同研究者から確保した。HPVタイプの判明している子宮頚癌の前癌病変である頸部上皮内新生物(CIN)におけるE4蛋白発現の検討を行ったところ、これまでの報告と同様にCINの中層から表層部にかけてE4蛋白の局在が観察された。調べて範囲内ではE4蛋白の発現は多いが、間質にある免疫担当細胞などにも染色されるため、これが単なる交差反応か意義のある所見かどうかについて検討している。今後、HPV型の判定結果を確定させてから、E4抗体のHPV型特異性についての検討を行う予定である。E4蛋白の免疫染色はHPV感染の診断に応用できる可能性があり、新しいHPVワクチンのターゲットとしてE4蛋白が有効である可能性がある。Certain human papillomavirus types named high-risk types are thought to cause cervical cancer and cervical intraepithelial neoplasia (CIN). It has been recently known that E4 proteins of these types are abundantly expressed in CIN epithelium. However, such expression has not been investigated extensively in clinical samples. This study is to examine the expression pattern using E4 antibodies for specific HPV types.We obtained seven different polyclonal antibodies against E4 proteins of HPV types 11, 16, 18, 31, 33, 56, which were produced from immunized rabbits and purified. lb start this experiment, we tried to do HPV genotyping in cytological samples using three different HPV genotyping methods in women who were abnormal in cytology. These methods are now commercially available in Japan. We found that different assays have shown discordant results in some of the samples examined. Discordant results were more frequently observed in the cases infected with different HPV types. This type of multiple HPV type infection were more common in women having abnormal cytology as we have previously expected. Now we are going to analyze more detail in these eases showing discordant results. This is a crucial step for further experiment for E4 study.E4 expression has been confirmed on epithelium from middle to superficial layers in most of CIN1 and CIN2, 3 lesions in which HPV types were determined. Abundant expression was seen in some cases. However, some immune cells were also stained by these antibodies. We have to figure out the positive reaction to immune cell is merely due to cross-reaction or due to presence of E4 in these immune cells. Furthermore, we have to test type-specificity of these antibodies in immune-staining. E4 protein immunostaining method may be useful for diagnostic purpose of high-risk HPV infection, and furthermore E4 might be a good target for therapeutic HPV vaccine.研究課題/領域番号:18591827, 研究期間(年度):2006-2007出典：「子宮頚部における高リスク型ヒトパピローマウイルスE4蛋白の発現と免疫応答」研究成果報告書　課題番号18591827 (KAKEN：科学研究費助成事業データベース（国立情報学研究所）)　　　本文データは著者版報告書より作

An Analysis of Factors that Exacerbate Asthma, Based on a Japanese Questionnaire

ABSTRACTBackgroundIt is known that a wide variety of factors exacerbate asthma; however, few studies have investigated the factors that exacerbate asthma from a patient's perspective. The aim of this study was to analyze the factors that exacerbate asthma, based on a questionnaire completed by asthma patients in Niigata Prefecture.MethodsBased on questionnaires given to 3085 patients who visited the medical institutes in the Niigata Prefecture monthly from September through October 2006, groups stratified by sex, age, disease type and disease severity, were analyzed for factors contributing to asthma exacerbation, as described in the guideline of the Japanese Society of Allergology.ResultsThe leading exacerbating factor chosen by patients was a change in the weather, followed by smoking, allergen exposure, fatigue, stimulants, and air pollutants. Respiratory infection, widely recognized as a critical factor of severe exacerbation, was ranked seventh. Allergen exposure and air pollutants were prominent in younger individuals, whereas respiratory infection tended to be more common in elderly subjects. Allergen exposure, air pollutants, and exercise were significantly more common in atopic-type patients, in contrast with respiratory infection in non-atopic-type patients. According to multiple regression analysis, poor asthma control during the last one year was associated with changes in the weather, whereas the non-atopic disease type was related to exacerbation by respiratory infection. Current smoking was associated with both factors.ConclusionsMany factors exacerbate asthma, depending on the individual case and his/her background. These data suggest that changes in the weather may be more important factor for patients in asthma exacerbation

Significance of Kampo, Traditional Japanese Medicine, in Supportive Care of Cancer Patients

The current standard treatment for cancer is a multidisciplinary therapy whereby various types of treatment are properly combined. Chemotherapy with multiple anticancer drugs is now common, and traditional, complementary, and alternative therapies are adopted as supportive measures. Medical care in Japan is distinguished by the ability for patients to access both Western and Kampo medical cares at the same time. There is a high degree of trust in the safety of Kampo therapies because they are practiced by medical doctors who are educated with fundamental diagnosis of Western medicine. Highly reliable clinical studies are being published, demonstrating that palliative or supportive care for cancer patients using Kampo preparations alleviates adverse effects of chemotherapy or radiotherapy. This paper reports the circumstances around cancer care in Japan where traditional therapeutic Kampo formulas are used for patients undergoing cancer treatment with cutting-edge chemotherapy, specifically to alleviate adverse effects of anticancer drugs

Androgen replacement therapy contributes to improving lower urinary tract symptoms in patients with hypogonadism and benign prostate hypertrophy: A randomised controlled study

金沢大学附属病院泌尿器科Purpose. We performed a randomised controlled study regarding the effects of androgen replacement therapy (ART) on lower urinary tract symptoms (LUTS) in hypogonadal men with benign prostate hypertrophy (BPH). Methods. Fifty-two patients with hypogonadism and BPH were randomly assigned to receive testosterone (ART group) as 250 mg of testosterone enanthate every 4 weeks or to the untreated control group. We compared International Prostate Symptom Score (IPSS), uroflowmetry data, post-voiding residual volume (PVR) and systemic muscle volume at baseline and 12 months after treatment. Results. Forty-six patients (ART group, n=23; control, n=23) were included in the analysis. At the 12-month visit, IPSS showed a significant decrease compared with baseline in the ART group (15.7±8.7 vs. 12.5 ± 9.5; p < 0.05). No significant changes were observed in the control group. The ART group also showed improvement in maximum flow rate and voided volume (p < 0.05), whereas no significant improvements were observed in the controls. PVR showed no significant changes in either group. In addition, the ART group showed significant enhancement of mean muscle volume (p < 0.05), whereas no significant changes were seen in the controls. Conclusion. ART improved LUTS in hypogonadal men with mild BPH. © 2010 Informa UK, Ltd