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Lydwina Juvanni Callestya
"Sindrom ovarium polikistik (SOPK) adalah salah satu kelainan endokrin yang paling umum terjadi pada wanita usia reproduktif. Patogenenesis SOPK berhubungan langsung dengan resistensi insulin. Beberapa studi menyimpulkan bahwa akupunktur dapat meningkatkan sensitivitas insulin sehingga dapat memperbaiki gejala SOPK. Uji klinis acak tersamar ganda dilakukan pada 44 penderita SOPK yang dibagi secara acak ke dalam dua kelompok, yakni kelompok elektroakupunktur kombinasi medikamentosa (n=22) dan kelompok elektroakupunktur sham kombinasi medikamentosa (n=22). Elektroakupunktur dilakukan 3 kal seminggu, sebanyak 12 kali, selama 4 minggu, pada titik CV3 Zhongji, CV4 Guanyuan, CV6 Qihai, ST25 Tianshu, ST28 Shuidao, ST36 Zusanli, SP6 Sanyinjiao, dan BL57 Chengsan. Pemeriksaan gula darah puasa dan insulin puasa dilakukan untuk mengukur indeks HOMA-IR sebagai luaran primer. Hasil penelitian menunjukkan adanya perbedaan yang bermakna. Median indeks HOMA-IR pada kelompok elektroakupunktur kombinasi medikamentosa sebelum dan sesudah terapi menunjukkan perbedaan bermakna secara statistik (p=0,014). Sedangkan median indeks HOMA-IR pada kelompok elektroakupunktur sham kombinasi medikamentosa sebelum dan sesudah terapi tidak terdapat perbedaan bermakna (p=0,592). Kesimpulan penelitian ini elektroakupunktur kombinasi medikamentosa efektif untuk meningkatkan sensitivitas insulin.

Polycystic ovary syndrome (SOPK) is one of the most common endocrine disorders in women of reproductive age. The pathogenesis of SOPK is directly related to insulin resistance. Several studies have concluded that acupuncture can increase insulin sensitivity to improve symptoms of PCOS. Double-blind randomized clinical trials were performed on 44 patients with SOPK who were randomly divided into two groups, the electroacupuncture with medication group (n=22) and the electroacupuncture sham with medication group (n=22). Electroacupuncture was given 3 times a week, 12 times, for 4 weeks, at the point of CV3 Zhongji, CV4 Guanyuan, CV6 Qihai, ST25 Tianshu, ST28 Shuidao, ST36 Zusanli, SP6 Sanyinjiao, and BL57 Chengsan. Fasting blood glucose and fasting insulin were performed to measure the HOMA-IR index as the primary outcome. The results showed a significant difference. The median HOMA-IR index in the electroacupuncture with medication group before and after therapy showed statistically significant differences (p = 0.014). While median HOMA-IR index in electroacupuncture sham with medication group before and after therapy there was no significant difference (p = 0.592). The conclusion of this study electroacupuncture combination with medication is effective to improve insulin sensitivity. "
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2018
SP-pdf
UI - Tugas Akhir  Universitas Indonesia Library
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Binahayati
"ABSTRAK
Sindrom metabolik MetS adalah kumpulan faktor yang kompleks dan saling berhubungan, yang meningkatkan risiko penyakit jantung dan diabetes mellitus tipe 2. Resistensi insulin dan obesitas sentral dianggap sebagai penyebab utama dari sindrom metabolik, sehingga penurunan resistensi insulin menjadi tujuan klinis yang penting saat ini. Beberapa studi menyimpulkan bahwa akupunktur dapat meningkatkan sensitivitas insulin, karena itu efektif untuk mengatasi gangguan metabolik Uji klinis acak tersamar tunggal dengan pembanding dilakukan pada 50 penderita sindrom metabolik yang dibagi secara acak ke dalam dua kelompok, kelompok elektroakupunktur dan medikamentosa n = 25 serta kelompok elektroakupunktur sham dan medikamentosa n=25 . Elektroakupunktur dilakukan 2 kali seminggu sebanyak 10 kali tindakan di titik CV12 Zhongwan, CV4 Guanyuan, ST25 Tianshu, ST36 Zusanli, ST40 Fenglong, SP6 Sanyinjiao, dan MA-IC3 Endokrin. Dilakukan pemeriksaan gula darah puasa dan insulin puasa untuk mengukur HOMA-IR sebagai luaran primer. Hasilnya terdapat perbedaan bermakna secara statistik perubahan HOMA-IR antara kelompok elektroakupunktur dan medikamentosa dengan kelompok elektroakupunktur sham dan medikamentosa -1,66 2,187 dan -0,29 2,388, p = 0,044 . Terapi kombinasi elektroakupunktur dan medikamentosa efektif untuk menurunkan resistensi insulin pada penderita sindrom metabolik.

ABSTRACT
The metabolic syndrome is a complex disorder defined by a cluster of interconnected factors that increase the risk of cardiovascular diseases and diabetes mellitus type 2. Insulin resistance and central obesity are considered significant factors as the underlying cause of the metabolic syndrome, since reduction of insulin resistance is an important clinical goal today. Several studies have concluded that acupuncture can improve insulin sensitivity, as it is effective against metabolic disturbances. A single blind randomized controlled trial involved 50 patients randomly allocated into two groups electroacupuncture with medication group n 25 or sham electroacupunture with medication group n 25 . Electroacupuncture therapy was given twice a week for ten times at CV12 Zhongwan, CV4 Guanyuan, ST25 Tianshu, ST36 Zusanli, ST40 Fenglong, SP6 Sanyinjiao, and MA IC3 Endocrine. Fasting blood glucose and fasting insulin serum were assessed to measure HOMA IR as the primary outcome. There was a statistically significant difference in changing of HOMA IR between electroacupuncture with medication group and sham electroacupunture with medication group 1,66 2,187 and 0,29 2,388, p 0.044 . Electroacupuncture with medical treatment effectively decreased insulin resistance of metabolic syndrome patients."
2017
SP-Pdf
UI - Tugas Akhir  Universitas Indonesia Library
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Wenny Kurniawan
"Sindrom ovarium polikistik (SOPK) merupakan suatu kondisi umum endokrinopati yang ditandai dengan adanya oligoovulasi atau anovulasi, produksi androgen berlebih, dan adanya kista ovarium kecil multipel yang diidentifikasi secara sonografis (kriteria Rotterdam, 2004). SOPK ditemukan pada 10% populasi wanita usia reproduksi dan berhubungan erat dengan disfungsi ovulasi sehingga menurunkan angka fertilitas. Tujuan penelitian ini adalah untuk mengetahui pengaruh terapi kombinasi elektroakupunktur dan medikamentosa terhadap SOPK. Uji klinis acak tersamar ganda dengan kontrol dilakukan terhadap 44 subjek dengan SOPK yang dialokasikan secara acak ke dalam kelompok elektroakupunktur sejati dan medikamentosa (n=22), serta kelompok elektroakupunktur sham dan medikamentosa (n=22). Penilaian menggunakan pencitraan USG transvaginal dan perhitungan panjang siklus menstruasi sebelum dan sesudah perlakuan. Hasil penelitian menunjukkan terdapat perbedaan bermakna rerata volume ovarium antara kedua kelompok sebelum dan sesudah perlakuan (p=0,002); penurunan jumlah folikel antral (p=0,005); angka kejadian menstruasi (p=0,001); dan pemendekan siklus menstruasi (p=0,003). Kesimpulan penelitian ini elektroakupunktur dan medikamentosa memberikan perbaikan terhadap keluhan dan gambaran ovarium pada pasien SOPK.

Polycystic Ovarian Syndrome (PCOS) is a general endocrinopathy condition that signed with oligoovulation or anovulation cycle, excess androgen production, and an image of multiple small cysts identified by transvaginal ultrasound (Rotterdam criteria, 2004). PCOS found in 10% of reproductive women and highly corresponded with ovulation dysfunction and finally decrease the fertility rate. The goal of this study is to know the effect of electroacupuncture combined with medical treatment in PCOS. A double blind randomized controlled trial is performed in 44 subjects with PCOS and divided into true electroacupuncture combined with medical treatment group (n=22) and sham electroacupuncture combined with medical treatment group (n=22). Ovarian volume and antral follicle are evaluated with transvaginal ultrasound and the length of menstrual cycle is counted before and after the treatment. The results show there are significant mean differences between ovarian volume in two groups before and after treatment (p=0,002); antral follicle count (p=0,005); menstrual incidence during the treatment (p=0,001); and shortened menstrual cycle (p=0,003). The conclusion of this study is electroacupuncture combined with medical treatment could improve PCOS patients’ compaint and ovarian image."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2018
T-Pdf
UI - Tesis Membership  Universitas Indonesia Library
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Desmawati
"Latar belakang: Sindrom ovarium polikistik (SOPK) merupakan salah satu kelainan endokrin paling umum pada 7-15% wanita usia reproduksi yang menyebabkan infertilitas anovulatori. SOPK sering ditemukan pada wanita gemuk, sekitar 50-75% tetapi sindrom ini juga dapat ditemukan pada wanita kurus sebesar 5,5%. Penyebab dan patogenesis SOPK sampai sekarang masih diperdebatkan tapi hasil penelitian memperlihatkan hiperandrogen dan resistensi insulin terlibat dalam perkembangan perjalanan penyakit dan fenotip SOPK. Efek androgen dimediasi oleh reseptor androgen (AR) sedangkan efek insulin dimediasi oleh reseptor insulin (INSR). Ekspresi dan aksi dari kedua reseptor ini terutama pada sel granulosa ovarium dapat dipengaruhi oleh mekanisme epigenetik yang diduga terlibat dalam perkembangan penyakit SOPK ini.
Tujuan: Mengetahui tingkat metilasi DNA pada gen reseptor androgen (AR) dan reseptor insulin (INSR) serta ekspresi mRNAnya pada sel granulosa subjek SOPK dan nir-SPOK.
Metode: Penelitian ini merupakan penelitian deskriptif analitik dengan rancangan cross sectional. Sampel berupa sel granulosa dari folikel ovarium didapatkan dari wanita yang melakukan ovum pick up (OPU) di klinik Yasmin RSUPN Ciptomangunkusumo yang kemudian dilakukan isolasi DNA dan RNA. Pada isolat DNA dilakukan konversi bisulfit, Methyl Specifik PCR (MSP), elektroforesis dan analisis ketebalan pita dengan perangkat lunak ImageJ untuk mendapatkan data tingkat metilasi DNA. Pada isolat RNA dilakukan qPCR untuk mendapatkan ekspresi relatif mRNA gen AR dan INSR.
Hasil: Analisis data dari 21 subjek SOPK dan 20 subjek nir SOPK menunjukkan terdapat perbedaan bermakna (p=0,00) tingkat metilasi DNA gen AR pada pasien SOPK (45.24 %±16,84) dibandingkan nir-SOPK (84,96±15,45). Analisis gen INSR, pada subjek SOPK 100% tidak terjadi metilasi pada promotor gen INSR tetapi pada subjek nir-SOPK 1 dari 21 wanita mengalami metilasi parsial ((37,82%±8,25). Dari penelitian juga didapatkan terjadinya peningkatan ekspresi relatif mRNA AR sebesar 2,459 kali dan 1,791 kali pada mRNA INSR. Tidak terdapat korelasi antara tingkat metilasi gen AR dan INSR dengan ekspresi mRNAnya.
Kesimpulan: Penurunan tingkat metilasi DNA (hipometilasi) pada gen AR dan INSR dapat meningkatkan tingkat ekspresi mRNA AR dan INSR, yang kemudian berkontribusi terhadap kejadian hiperandrogen dan resistensi insulin pada fenotip subjek SOPK.

Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in 7-15% of women of reproductive age who cause anovulatory infertility. PCOS is often found in obese women, around 50-75% but this syndrome can also be found in thin women at 5.5%. The causes and pathogenesis of PCOS is still debated but the results of the study show hyperandrogen and insulin resistance involved in the development of the disease course and the PCOS phenotype. The androgen effect is mediated by the androgen receptor (AR) while the effect of insulin is mediated by the insulin receptor (INSR). The expression and action of these two receptors, especially in ovarian granulosa cells can be influenced by epigenetic mechanisms that are thought to be involved in the development of PCOS.
Objective: To determine the level of DNA methylation in the androgen receptor gene (AR) and insulin receptor (INSR) and its mRNA expression in the SOPK and nir-SPOK granulosa cells.
Method: This study is a descriptive analytic study with a cross sectional design. Samples in the form of granulosa cells from ovarian follicles were obtained from women who performed ovum pick up (OPU) at the Yasmin clinic Ciptomangunkusumo Hospital which was then isolated from DNA and RNA. DNA isolates were carried out bisulfite conversion, Methyl Specific PCR (MSP), electrophoresis and tape thickness analysis with ImageJ software to obtain DNA methylation level data. QPCR was performed on RNA isolates to obtain the relative expression of the AR and INSR mRNA genes.
Results: Analysis of data from 21 SOPK subjects and 20 non-PCOS subjects showed significant differences (p = 0.00) of AR gene DNA methylation rates in PCOS patients (45.24% ± 16.84) compared to non-PCOS (84.96 ± 15 , 45). INSR gene analysis, in the subject of 100% PCOS there was no methylation of the INSR gene promoter but in non-PCOS subjects 1 out of 21 women had partial methylation ((37.82% ± 8.25). AR is 3.459 times and 2.791 times in INSR mRNA. There is no correlation between the rate of methylation of the AR and INSR genes with their mRNA expression.
Conclusion: Decreasing levels of DNA methylation (hypomethylation) in AR and INSR genes can increase the level of expression of mRNA AR and INSR, which then contributes to the incidence of hyperandrogen and insulin resistance in the phenotype of the PCOS subject.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2018
T-pdf
UI - Tesis Membership  Universitas Indonesia Library
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Rizka Yurianda
"Ketimpangan antara kadar vitamin D25(OH) rendah dan keadaan resistensi insulin pada penderita SOPK dengan anovulasi kronik menarik untuk digali lebih jauh. Anovulasi kronik pada SOPK diyakini disebabkan terhentinya pertumbuhan folikel di ovarium. Pada resistensi insulin, vitamin D diperkirakan berperan di sel sasaran dengan menambah substrat reseptor insulin. Perlu diungkap pengaruh vitamin D terhadap pertumbuhan folikel ovarium dengan mengukur kadar AMH, kemudian diperbandingkan antara penderita S-OPK-RI dan SOPK-nir-RI berdasarkan perubahan kadar reseptor insulin darah. Penelitian ini bertujuan menentukan pengaruh pemberian vitamin D3 terhadap pertum-buhan folikel ovarium dan penurunan kadar AMH melalui jalur reseptor insulin dan resep-tor vitamin D darah. Penelitian dua tahap dilakukan dari 14 Agustus 2018 hingga 25 Fe-bruari 2019 terhadap 35 subjek SOPK-RI dan 35 subjek SOPK-nir-RI di Poliklinik Infer-tilitas dan Endokrinologi Departemen Obstetri dan Ginekologi RSPAD Gatot Soebroto (RSGS), Jakarta. Tahap pertama adalah iris-silang antara SOPK-RI dan nir-RI untuk mem-bandingkan kadar vitamin D25(OH), AMH, reseptor insulin dan reseptor vitamin D darah. Tahap kedua adalah uji kuasi-eksprimental untuk mengetahui pengaruh pemberian vitamin D3 12.000 IU per minggu selama tiga bulan terhadap pertumbuhan folikel dengan peman-tauan USG-transvaginal atau transrektal sebulan sekali dan kadar AMH pada SOPK-RI dan nir-RI. Kadar glukosa puasa, insulin puasa, vitamin D25(OH), AMH diukur dari darah. Reseptor vitamin D darah dan reseptor insulin darah diperiksa dari sel mononukleus darah tepi (SMDT). Hasil penelitian memperlihatkan bahwa: (1) prapemberian vitamin D3 nilai yang berbeda bermakna antara SOPK-RI dan SOPK-nir-RI adalah kadar glukosa puasa (84 vs. 78 mg/dL; p = 0,016), insulin puasa (20,3 vs. 7,49 μIU/mL; p < 0,001) (2) pascapemberian vitamin D3 yang berbeda bermakna adalah kadar glukosa puasa (82 vs. 79 mg/dL; p = 0,049), insulin puasa (23,19 vs. 10,54; p < 0,001), reseptor insulin lebih tinggi pada SOPK-RI diban-dingkan SOPK-nir-RI (18,80 vs. 14,78 ng/mL; p = 0,020), reseptor vitamin D pada SOPK-nir-RI menurun bermakna (63,29%); (3) pascapemberian vitamin D3 ditemukan: (a) delta perubahan kadar vitamin D25(OH) pasca (8,38 ng/mL (63,4%) [SD 4,06] SOPK-RI vs. 12,31 ng/mL (10,29%) SOPK-nir-RI, p < 0,001); (b) delta perubahan penurunan kadar AMH pasca SOPK RI 10,29 vs. SOPK-nir-RI 14,61%; p = 0,492); (c) delta peningkatan diameter folikel antara dua kelompok SPOK meningkat pada bulan pertama (14,3% vs. 50%), kedua (33,3% vs. 66,7%), dan ketiga (50% vs. 66,7%), tetapi yang berbeda bermak-na (p < 0,05) hanya pada bulan pertama, yaitu lebih besar pada SOPK-nir-RI. Disimpulkan bahwa vitamin D3 menurunkan kadar AMH pada SOPK-RI dan SOPK-nir-RI, serta meningkatkan pertumbuhan folikel pada kededua kelompok SOPK, pada bulan pertama perubahan diameter folikel lebih besar pada SOPK nir-RI. Prapemberian vitamin D3 tidak ditemukan perbedaan kadar reseptor insulin dan reseptor vitamin D pada kededua kelompok SOPK, sedangkan pascapemberian vitamin D3 terdapat penurunan kadar reseptor vitamin D pada SOPK-nir-RI.

Discrepancy between low-level vitamin 25(OH)D and insulin resistance in PCOS patients with chronic anovulation required to be further explored. Chronic anovulation in PCOS is believed to be caused by the follicular arrest in the ovary. In insulin resistance the vitamin D is thought to play a role in target cell by adding the insulin receptor substrate. It is nec-essary to elucidate the effect of vitamin D on the ovarian folliculogenesis by measuring the AMH levels, which are then compared between patients with IR-PCOS and non-IR-PCOS based on the changes in blood insulin receptor levels. The aim of this study is to determine the effect of vitamin D3 administration on ovarian follicular growth and reduction of AMH through insulin receptor and blood vitamin D re-ceptor pathways. The two stages study was carried out from 14th August 2018 to 25th February 2019 on 35 IR-PCOS and 35 non-IR-PCOS subjects at the Infertility and Endo-crinology Out-patient Clinic, Department of Obstetrics and Gynecology, Gatot Soebroto Central Army Hospital (RSGS), Jakarta. The first stage was a cross-section study between IR-PCOS and non-IR-PCOS to compare levels of vitamin 25(OH)D, AMH, blood insulin receptors and vitamin D receptors; the second is a quasi-experimental test to determine the effect of 12,000 IU vitamin D3 administration per week for 3 months on follicular growth with transvaginal or transrectal ultrasound monthly and AMH levels on IR-PCOS-and non-IR-PCOS. Fasting glucose, fasting insulin, vitamin D25(OH), AMH levels are measured from the blood. Blood vitamin D receptor and insulin receptor were measured from the peripheral blood mononuclear cells (PBMC). The results of the study demonstrated that: (1) before administration of vitamin D3, there were differences in fasting glucose (84 vs. 78 mg/dL; p = 0.016) and fasting insulin (20.3 vs. 7.49 μIU/mL; p < 0.001) between the two groups; (2) after vitamin D3 administration, significant differences were found between the two groups for the levels of fasting glucose (82 vs. 79 mg / dL; p = 0.049), fasting insulin (23.19 vs. 10.54; p < 0.001); higher insulin receptors was found in IR-PCOS compared to non-IR-PCOS (18.80 vs. 14.78 ng / mL; p = 0.020), the vitamin D receptors in non-IR-PCOS decreased significantly (63.29%); (3) vitamin 25(OH)D levels before vitamin D3 administration were not significantly different in the two groups (13.84 vs. 10.97 ng/mL; p = 0.327), while after vitamin D3 administration the levels increased significantly (8.38 ng/mL (63.4%) [SD 4.06] in IR-PCOS vs. 12.31 ng/mL (10.29%) in non-IR-PCOS, p < 0.001); (4) AMH levels decreased in the both groups after vitamin D3 admin-istration but the ratio of the decrease was not significantly different (10.29 vs. 14.61%; p = 0.492); (5) follicular diameter between the two groups increased in the first month (14.3% vs. 50%), the second month (33.3% vs. 66.7%), and the third month (50% vs. 66.7% ) after vitamin D3 administration, but the significant difference (< 0.05) was demonstrated only in the first month, which was greater in non-IR-PCOS than that in the IR-PCOS. It is concluded that vitamin D3 decreases AMH levels in both IR-PCOS and non-IR-PCOS. It increases folliculogenesis in both PCOS groups; in the first month, the changes in follic-ular diameter are greater in non-IR-PCOS. Before vitamin D3 administration, there is no difference in the levels of insulin receptors and vitamin D receptors between the two groups, whereas after vitamin D3 administration there is a decrease in the levels of vitamin D re-ceptors in non-IR-PCOS. Keywords: AMH, IR-PCOS, non-IR-PCOS, PBMC, vitamin D receptor, insulin receptor, vitamin D25(OH)."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2019
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UI - Disertasi Membership  Universitas Indonesia Library
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Cynthia Agnes Susanto
"TUJUAN: Mengetahui efek metformin atau DLBS3233 terhadap kadar AMH.
LATAR BELAKANG: SOPK merupakan sindrom yang diketahui berkaitan dengan resistensi insulin dalam patofisiologi dan peranan AMH dalam patogenesis. Maka salah satu bagian dari tatalaksana SOPK adalah dengan pemberian insulin sensitizing agent ISA. ISA yang telah banyak digunakan yaitu metformin yang terbukti dalam memperbaiki siklus haid, namun obat ini juga menimbulkan efek samping seperti keluhan gastrointestinal yang cukup berat. Sehingga perkembangan obat herbal seperti fraksi bioaktif DLBS3233 memberikan harapan akan ISA yang efektif, namun memiliki efek samping minimal. Peranan ISA dalam efek perubahan AMH masih kontroversial, dan hanya ditemui penelitian yang meneliti metformin.
DESAIN DAN METODE: Penelitian ini menggunakan desain uji klinis acak tersamar ganda yang berlangsung pada bulan Maret 2013 hingga Juni 2015 di klinik Yasmin, RSCM Kencana dan RS Hasan Sadikin, Bandung. Subjek penelitian akan mendapatkan metformin sebanyak 2x750mg atau DLBS3233 1x100mg per hari selama enam bulan. Evaluasi kadar AMH akan dilakukan sebanyak dua kali, sebelum dan sesudah pengobatan.
HASIL: Sebanyak 20 subjek mendapati metformin dan 18 subjek mendapati DLBS3233. Rerata kadar AMH sebelum pengobatan didapati 9,30 5,06 ng/mL dan 11,27 6,47 ng/mL. Pasca pengobatan, didapati penurunan kadar AMH yang signifikan sebesar 1,52 0,07 p < 0,001. Penurunan kadar AMH didapati lebih tinggi pada grup metformin bila dibandingkan dengan DLBS3233 ? AMH = 1,83 ng/mL vs 1,15 ng/mL. Namun, metformin menimbulkan efek samping yang lebih signifikan dibandingkan DLBS3233 p=0,01. Sebanyak 7 pasien 18,42 hamil selama penelitian ini. Namun efek samping pengobatan jauh dirasakan oleh subjek yang mendapatkan metformin dibandingkan DLBS3233 p=0,01.
KESIMPULAN: Baik metformin atau fraksi bioaktif DLBS3233 dapat menurunkan kadar AMH, dan DLBS3233 merupakan pilihan terapi SOPK dengan efek samping yang minimal.

OBJECTIVE: To determine the effect of metformin and DLBS3233 on serum AMH level.
BACKGROUND: PCOS is known to be associated with insulin resistance in the pathophysiology and Anti Mullerian Hormone AMH in the pathogenesis. Thus, one of management of PCOS is to give insulin sensitizing agent ISA. Type of ISA which has been widely used is metformin which proven to improve menstrual cycle, but this medication cause major side effect such as gastrointestinal problems. So, the development of herbal medicine such as Bioactive Fraction DLBS3233, offer effective medicine, with minimal side effects. To date, the role of ISA to effects the changes in AMH still controversial, and studies only examine the effect of metformin to the level of AMH.
METHOD: Double blind randomized controlled trial was conducted in Yasmic Clinic, Cipto Mangunkusumo General Hospital, Kencana and Hasan Sadikin hospital, Bandung within March 2013 until June 2015. PCOS patient diagnosed using Rotterdam All participant get daily dose of metformin 2x750mg or DLBS3233 1x100mg for six months. Evaluation of serum AMH level was conducted twice prior therapy and after the completion of the therapy. Protocol analysis was carried out upon differences of AMH using SPSS 20.
RESULTS: 20 subjects received metformin, while 18 subject received DLBS3233. Level of AMH prior medication was known to be 9,30 5,06 ng mL and 11,27 6,47 ng mL. After six months of therapy, there is significant decrease of AMH level of 1,52 0,07 p 0,001. The decrease level of AMH was observed higher in metformin group compared to DLBS3233 AMH 1,83 ng mL vs 1,15 ng mL. However, metformin causing more side effects compared to DLBS3233 p 0,01. There are total of 7 subjects 18,42 pregnant during the studies.
CONCLUSION: There rsquo s a significant decrease of AMH level after administration of either metformin or DLBS3233.
"
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2016
T58727
UI - Tesis Membership  Universitas Indonesia Library
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Vita Silvana
"ABSTRAK
Latar Belakang: Sindrom Ovarium Polikistik (SOPK) merupakan penyebab 40%
infertilitas pada wanita usia reproduksi. Resistensi insulin sebagai salah satu
patofisiolofi yang mendasari SOPK, berkaitan erat dengan jaringan adiposa
viseral dan ditemukan pada 30-50% pasien SOPK dengan indeks masa tubuh
normal serta lingkar pinggang kurang dari 80 cm. Retinol Binding Protein-4
(RBP-4) yang disekresi oleh jaringan adiposa viseral diketahui sebagai salah satu
adipokin yang menyebabkan resistensi insulin. Pengukuran IMT dan lingkar
pinggang tidak dapat mewakili akumulasi jaringan adiposa viseral pada SOPK
dengan IMT normal serta lingkar pinggang kurang dari 80 cm. Dengan
diketahuinya titik potong optimal kadar serum RBP-4 sebagai penanda jaringan
adiposa viseral, diharapkan dapat memprediksi risiko kejadian resistensi insulin
yang bermanfaat dalam menentukan penatalaksanaan kasus SOPK dengan IMT
normal terkait strategi pengurangan akumulasi jaringan adiposa viseral.
Tujuan: Diketahuinya titik potong optimal kadar serum RBP-4 sebagai penanda
jaringan adiposa viseral untuk memprediksi risiko kejadian resistensi insulin pada
penderita SOPK dengan IMT normal.
Metode: Studi observasional dengan desain potong lintang selama periode Juli
2014 hingga Maret 2015 di Poliklinik Yasmin, RSCM, Jakarta.
Hasil: Sejumlah 40 subjek SOPK dengan IMT normal yang memenuhi kriteria
inklusi didapatkan 16 subjek (40%) yang mengalami resistensi insulin dan 24
subjek (60%) nir resistensi insulin. Sejumlah 23 subjek (57.5%) memiliki lingkar
pinggang kurang dari 80 cm, dimana 6 subjek (26%) diantaranya mengalami
resistensi insulin. Kadar serum RBP-4 pada kelompok resistensi insulin bermakna
lebih tinggi dibandingkan nir resistensi insulin (p 0.008). Dengan analisis ROC
didapatkan AUC kadar serum RBP-4 78.8% (IK 95% -8445.59 ? -1447.98)
dengan nilai p 0.002. Titik potong optimal kadar serum RBP-4 adalah 24133
ng/mL dengan sensitivitas sebesar 75% dan spesifisitas sebesar 75%. Dengan
analisis regresi logistik biner didapatkan pemeriksaan serum RBP-4 menambah
nilai diagnostik dari parameter demografis dan klinis AUC 85.7% menjadi 91.1%.
Kesimpulan: Kadar serum RBP-4 sebagai penanda jaringan adiposa viseral dapat digunakan untuk memprediksi risiko kejadian resistensi insulin pada penderita SOPK dengan IMT normal. ABSTRACT Background: Polycystic ovarian syndrome (PCOS) contributes to fourty percent
of infertility?s issues on reproductive women. Insulin resistance as one of
important pathophysiology in PCOS, correlates with visceral adipose tissue and is
found on 30-50% PCOS patients with normal body mass index and waist
circumference less than 80 cm. Retinol Binding Protein-4 (RBP-4), which is
secreted by visceral adipose tissue, known as one of adipokines that cause insulin
resistance. The measurement of body mass index and waist circumference could
not represent visceral adiposity on PCOS with normal body mass index and waist
circumference less than 80 cm. Determination of serum RBP-4 cut off level as
visceral adipose tissue marker hopefully could predict the risk of insulin
resistance on polycystic ovarian syndrome with normal body mass index,
therefore it will be useful on its management related to reduction of visceral
adiposity.
Objective: To obtain serum RBP-4 cut off level as visceral adipose tissue marker
to predict the risk of insulin resistance on PCOS with normal body mass index.
Method: This was an observational study with cross sectional design conducted at
Yasmin Clinic, RSCM, Jakarta during a period of July 2014 until March 2015.
Result: Fourty PCOS patients with normal body mass index were participated on
this study. There were 16 subjects (40%) who were insulin resistance and 24
subjects (60%) who were not insulin resistance. There were 23 subjects (57.5%)
who had waist circumference less than 80 cm, where 6 of them (26%) were
insulim resistance. Serum RBP-4 level was significantly higher on insulin
resistance group (p 0.008). After ROC analysis was performed, AUC of serum
RBP-4 was 78.8% (CI 95% -8445.59 ? -1447.98, p 0.002). The cut off level of
serum RBP-4 was 24133 ng/mL with sensitivity 75% and specificity 75%. After
logistic regression analysis was performed, it was found that serum RBP-4 increase diagnostic value of demographic and clinical parameter with AUC 85.7% to 91.1%. ;Background: Polycystic ovarian syndrome (PCOS) contributes to fourty percent
of infertility?s issues on reproductive women. Insulin resistance as one of
important pathophysiology in PCOS, correlates with visceral adipose tissue and is
found on 30-50% PCOS patients with normal body mass index and waist
circumference less than 80 cm. Retinol Binding Protein-4 (RBP-4), which is
secreted by visceral adipose tissue, known as one of adipokines that cause insulin
resistance. The measurement of body mass index and waist circumference could
not represent visceral adiposity on PCOS with normal body mass index and waist
circumference less than 80 cm. Determination of serum RBP-4 cut off level as
visceral adipose tissue marker hopefully could predict the risk of insulin
resistance on polycystic ovarian syndrome with normal body mass index,
therefore it will be useful on its management related to reduction of visceral
adiposity.
Objective: To obtain serum RBP-4 cut off level as visceral adipose tissue marker
to predict the risk of insulin resistance on PCOS with normal body mass index.
Method: This was an observational study with cross sectional design conducted at
Yasmin Clinic, RSCM, Jakarta during a period of July 2014 until March 2015.
Result: Fourty PCOS patients with normal body mass index were participated on
this study. There were 16 subjects (40%) who were insulin resistance and 24
subjects (60%) who were not insulin resistance. There were 23 subjects (57.5%)
who had waist circumference less than 80 cm, where 6 of them (26%) were
insulim resistance. Serum RBP-4 level was significantly higher on insulin
resistance group (p 0.008). After ROC analysis was performed, AUC of serum
RBP-4 was 78.8% (CI 95% -8445.59 ? -1447.98, p 0.002). The cut off level of
serum RBP-4 was 24133 ng/mL with sensitivity 75% and specificity 75%. After
logistic regression analysis was performed, it was found that serum RBP-4 increase diagnostic value of demographic and clinical parameter with AUC 85.7% to 91.1%. "
Fakultas Kedokteran Universitas Indonesia, 2015
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Amalia Shadrina
"Pada perempuan nir-obese dengan SOPK perlu dicari tahu mengenai apa saja faktor yang berpengaruh terhadap patofisiologi terjadinya SOPK. Sejumlah faktor diketahui menjadi penyebab dalam patofisiologi terjadinya SOPK, termasuk faktor epigenetik. Namun, sampai saat ini belum ada yang menyatakan mengenai faktor yang menjadi penyebab utama serta korelasi sejumlah faktor tersebut, seperti metilasi DNA reseptor insulin dan juga kadar insulin, dengan Free Androgen Index (FAI) pada SOPK nirobese. Sehingga penelitian ini bertujuan untuk menilai korelasi antara gonadotropin, profil antropometri, metilasi DNA reseptor insulin, kadar insulin dengan Free Androgen Index (FAI) pada subjek dengan Sindrom Ovarium Polikistik (SOPK) nir-obese. Dilakukan studi potong lintang pada 43 perempuan nir-obese di Jakarta yang dibagi menjadi 2 kelompok, yaitu kelompok positif dengan SOPK dan kelompok tanpa SOPK. Pemeriksaan dilakukan pada sejumlah variabel seperti usia, IMT, lingkar pinggang, kadar FSH, kadar LH, level metilasi reseptor insulin, dan FAI, kemudian dianalisis secara statistik. Diperoleh level metilasi reseptor insulin yang berkorelasi positif dengan tingkat korelasi sedang ((p = 0.01, r = 0.53), juga pada nilai LH (p = 0.02, r = 0.5). Sementara nilai SHBG pada kelompok SOPK nir-obese menunjukkan korelasi negatif dengan tingkat korelasi sedang (p = 0.02, r = -0.5). Terdapat asosiasi signifikan antara kadar SHBG dengan FAI baik pada kelompok SOPK maupun kelompok kontrol, juga ditemukannya korelasi negatif pada kedua kelompok, serupa dengan yang terdapat pada nilai LH. Kondisi ini tanpa disertai hubungan bermakna dari insulin yang menunjukkan bahwa SHBG dan LH merupakan suatu faktor independen dari patofisiologi terjadinya SOPK. Korelasi negatif pada metilasi reseptor insulin menunjukkan terjadi silencing pada fungsi reseptor insulin, sehingga terjadi penurunan sensitivitas dari reseptor insulin dan berujung pada meningkatnya kadar FAI.

Many factors that corresponding to pathophysiology of PCOS on lean women with PCOS. Some factors were still needed to be evaluated such as epigenetics, but until now no studies explaining about main cause and also correlation of those factors, including DNA methylation of insulin receptor and also insulin level, with Free Androgen Index (FAI) of lean PCOS. The aim of this study to evaluate the correlation between gonadotropin, anthropometric profile, DNA methylation of insulin receptor, insulin level, with Free Androgen Index (FAI) on Lean People with Polycystic Ovary Syndrome. A cross-sectional study included 43 lean women in Jakarta was done, and subjects were further classified into two groups, with PCOS and without PCOS. Several related variables such as age, body mass index (BMI), waist circumference, FSH level, LH level, DNA methylation of insulin receptor, insulin level, and FAI, were assessed and analyzed statistically. The DNA methylation of insulin receptor showed positive correlation with moderate correlation (p = 0.01, r = 0.53), and also to LH level (p = 0.02, r = 0.5). While SHBG level of lean PCOS group showed negative correlation with moderate correlation (p = 0.02, r = -0.5). Significance association was resulted between SHBG level and FAI of both groups, also found in LH level. This condition was found without significance association of insulin level which conclude that SHBG and LH level were independent factor of PCOS pathophysiology. Negative correlation of DNA methylation of insulin receptor showed silencing process of insulin receptor function, then decrease the sensitivity of insulin receptor which ended to increasing FAI level."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2019
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Roselina Panghiyangani
"Pendahuluan: Sindroma ovarium polikistik (SOPK) merupakan masalah reproduksi yang sering terjadi pada perempuan usia reproduksi, namun hingga saat ini etiopatogenesis SOPK masih belum jelas. Penelitian ini bertujuan menganalisis peran sel granulosa folikel ovarium dalam etiologi SOPK, keterkaitan genotip FSHR Asn680Ser dengan patogenesis SOPK dan peran gen CYP19A1(aromatase) dalam patogenesis SOPK.
Metode: Penelitian ini menggunakan desain penelitian analitik observasional berbentuk studi seran lintang (cross sectional study) dan dilakukan di Departemen Biologi FKUI, Klinik Yasmin-RSCM Kencana dan Laboratorium terpadu FKUI pada tahun 2011-2014. Sebanyak 142 subyek penelitian (66 pasien SOPK dan 76 pasien bukan SOPK) terlibat dalam penelitian ini. Sampel penelitian berupa darah tepi dan cairan folikel ovarium yang diaspirasi ketika proses ovum pick up sebagai sumber sel granulosa. Dilakukan isolasi DNA untuk analisis RFLP polimorfisme FSHR Asn680Ser, dilakukan kultur sel granulosa untuk mengetahui kemampuan proliferasi sel granulosa dan analisis ekspresi mRNA aromatase sel granulosa dengan metode RT-qPCR.
Hasil: Indeks proliferasi sel dan ekspresi mRNA aromatase sel granulosa pada kelompok SOPK lebih rendah secara bermakna dibandingkan bukan SOPK (p<0,05). Tidak ditemukan perbedaan bermakna distribusi genotip FSHR Asn680Ser antara kelompok SOPK dan bukan SOPK (p>0,05), tidak ditemukan perbedaan bermakna antara kadar hormon FSH basal berdasarkan variasi genotip FSHR Asn680Ser pada kelompok SOPK dan bukan SOPK (p>0,05). Tidak ditemukan perbedaan yang bermakna indeks proliferasi sel granulosa berdasarkan variasi genotip FSHR Asn680Ser baik pada kelompok SOPK maupun bukan SOPK (p>0,05). Tidak terdapat korelasi antara indeks proliferasi sel granulosa dengan ekspresi mRNA aromatase (p>0,05).
Kesimpulan: Indeks proliferasi sel dan tingkat ekspresi mRNA aromatase sel granulosa kelompok SOPK menurun dibandingkan kelompok bukan SOPK. Genotip FSHR Asn680Ser tidak menentukan kerentanan individu untuk menderita SOPK. Kadar hormon FSH basal dan indeks proliferasi sel granulosa tidak berbeda antara kelompok SOPK dan bukan SOPK berdasarkan variasi genotip FSHR Asn680Ser. Tidak ada korelasi antara indeks proliferasi sel dengan ekspresi mRNA aromatase sel granulosa pada penelitian ini.

Introduction: Polycystic ovary syndrome (PCOS) is a common reproductive problem in women at reproductive age, but until now aetiopathogenesis of PCOS has not been fully understood. The objective of this study was to analyse interrelationship between proliferation of ovarian follicular granulosa cells, CYP19A1 expression and polymorphism at codon 680 of FSHR towards the etiology of PCOS.
Methods: Observational analytic in the form of cross-sectional study was used in this research. The study was carried out between 2011-2014 at the Department of Biology, Integrated laboratory of Faculty of Medicine University of Indonesia and Yasmin clinic at the Cipto Mangunkusumo Hospital. A total of 142 subjects (66 patients with PCOS and 76 patients without PCOS) were involved in this study. Granulosa cells for culture were obtained from ovarian follicular fluid and total RNA was isolated from the cells. DNA samples were extracted from peripheral blood. Granulosa cell proliferation index was determined by counting under a phase-contrast microscope. CYP19A1 expression was measured by qRT-PCR, whereas polymorphism at Asn680Ser FSHR was performed by RFLP.
Result: Cell proliferation index and CYP19A1 mRNA expression levels in the granulosa cells of the PCOS group was significantly lower than non-PCOS (p < 0.05). There was no significant difference found in Asn680Ser FSHR genotype distribution between PCOS and non-PCOS group (p > 0.05). Based on Asn680Ser FSHR genotype variation, no significant difference was found between basal FSH hormone levels in the PCOS and non- PCOS group (p > 0.05) and FSHR genotype variation did not correlate with granulosa cell proliferation index between PCOS and non-PCOS group (p > 0.05). Moreover, there was no correlation between the granulosa cell proliferation index with aromatase mRNA expression levels (p > 0.05).
Conclusion: Cell proliferation index and CYPA1 expression of granulosa cells in PCOS group were lower compared to the non PCOS group although no correlation was found between the two parameters. Asn680Ser FSHR genotype did not correlate with individual susceptibility to PCOS. FSHR genotype variation did not correlate with basal FSH levels and granulosa cell proliferation index between PCOS and non-PCOS.
"
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2015
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Livy Bonita Pratisthita
"Latar Belakang. Prevalensi sindrom metabolik (SM) semakin meningkat di daerah rural
Indonesia. Kunci patogenesis SM adalah resistensi insulin yang dapat didiagnosis dengan
Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) dan Indeks
Triglyceride/Glucose (TyG). Hingga saat ini, belum ada nilai titik potong optimal untuk
indeks tersebut di Indonesia.
Metode. Sebanyak 1300 subjek orang dewasa berusia 18-60 tahun dari studi Sugarspin di
Nangapanda, Flores, Indonesia dibagi menjadi dua grup berdasarkan jenis kelamin.
Penentuan nilai titik potong HOMA-IR dan Indeks TyG pada setiap grup dilakukan dengan
kalkulasi persentil 75 (p75) dan 90 (p90) pada populasi sehat dan dengan metode receiver
operating characteristics (ROC) pada populasi SM dan non-SM. Korelasi antara HOMAIR
dan Indeks TyG dinilai dengan korelasi Spearman pada subjek laki-laki dan perempuan.
Hasil. Berdasarkan kedua metode, titik potong HOMA-IR dan Indeks TyG berbeda-beda
antara laki-laki dan perempuan. Nilai titik potong HOMA-IR berdasarkan persentil pada
laki-laki sehat adalah 0,9 (p75) dan 1,242 (p90); sedangkan pada perempuan adalah 1,208
(p75) dan 1,656 (p90). Berdasarkan ROC, titik potong HOMA-IR antara populasi SM dan
non-SM pada laki-laki adalah 1,185 dan pada perempuan adalah 1,505. Nilai titik potong
Indeks TyG pada laki-laki sehat adalah 8,590 (p75) dan 8,702 (p90); sedangkan pada
perempuan adalah 8,448 (p75) dan 8,617 (p90). Berdasarkan ROC, titik potong Indeks TyG
adalah 8,905 untuk laki-laki dan 8,695 untuk perempuan. Koefisien korelasi HOMA-IR
dan Indeks TyG ialah 0,39 pada laki-laki dan 0,36 pada perempuan.
Kesimpulan. Nilai titik potong HOMA-IR untuk resistensi insulin pada laki-laki adalah
0,9 (p75), 1,242 (p90), dan 1,185 (ROC); pada perempuan adalah 1,208 (p75), 1,656 (p90),
dan 1,505 (ROC). Nilai titik potong Indeks TyG pada laki-laki adalah 8,59 (p75), 8,702
(p90), dan 8,905 (ROC); pada perempuan adalah 8,448 (p75), 8,617 (p90), dan 8,695
(ROC). Didapatkan hasil korelasi yang lemah antara HOMA-IR dan Indeks TyG.

Background. Metabolic Syndrome (MS) prevalence is increasing in Indonesia's rural area.
The key pathogenetic mechanism of MS is insulin resistance which can be diagnosed by
Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and
Triglyceride/Glucose (TyG) Index. There are no predefined cut-offs for these indexes in
Indonesia.
Methods. As many as 1300 adults aged 18-60 years from Sugarspin study in Nangapanda,
Flores, Indonesia were divided into different groups based on sex. We determined the cutoff
points of HOMA-IR and TyG Index in each group by calculation of the 75th (p75) and
90th percentiles (p90) in healthy subjects and by receiver operating characteristics (ROC)
analysis of MS and non-MS subjects. Correlation between HOMA-IR and TyG Index was
performed in both sexes by Spearman's correlation.
Results. Using both methods, HOMA-IR and TyG Index cut-offs were different between
males and females. The HOMA-IR cut-offs for healthy males were 0.9 (p75) and 1.242
(p90); for healthy females were 1.208 (p75) and 1.656 (p90). By ROC, the HOMA-IR cutoff
for males was 1.185 and for females was 1.505. The TyG Index cut-offs for healthy
males were 8.590 (p75) and 8.702 (p90); for healthy females were 8.448 (p75) and 8.617
(p90). The TyG Index ROC cut-offs were 8.905 for males and 8.695 for females. The
correlation coefficients between HOMA-IR and TyG Index were 0.39 for males and 0.36
for females.
Conclusion. The HOMA-IR cut-offs for males were 0.9 (p75), 1.242 (p90), and 1.185
(ROC); for females were 1.208 (p75), 1.656 (p90), and 1.505 (ROC). The TyG Index cutoffs
for males were 8.590 (p75), 8.702 (p90), and 8.905 (ROC); for females were 8.448
(p75), 8.617 (p90), and 8.695 (ROC). The correlation between HOMA-IR and TyG Index
was weak.
"
Depok: Fakultas Kedokteran Universitas Indonesia, 2020
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