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1.
Artigo em Inglês | MEDLINE | ID: mdl-38571378

RESUMO

OBJECTIVE: Clinical characteristics of patients with endometrioma without dysmenorrhea have not been well delineated; our goal was to remedy this issue by performing a retrospective cohort study. METHODS: A total of 379 patients who underwent laparoscopic surgery for endometrioma ≥4 cm at a tertiary hospital were included in this retrospective study. Patients were divided into two groups based on the presence of dysmenorrhea at the time of hospital visit; with dysmenorrhea group and without dysmenorrhea group. RESULTS: Patients without dysmenorrhea comprised 9.5% of all surgically confirmed endometriomas. Significant differences were found in the revised American Society for Reproductive Medicine (rASRM) stage, age at surgery, and bilaterality. Patients with rASRM stage IV were more likely to have dysmenorrhea than were subjects with rASRM stage III (odds ratio (OR), 10.58; 95% confidence interval (CI), 4.63-24.21; P < 0.001). Older patients were less likely to have dysmenorrhea (OR, 0.94; 95% CI, 0.88-1.00; P = 0.045), as were patients with bilateral rather than unilateral endometrioma (OR, 0.36; 95% CI, 0.15-0.82; P = 0.015). No significant differences in cyst size, age at menarche, body mass index (BMI), parity, or history of previous ovarian surgery were found between the two groups. CONCLUSION: Patients without dysmenorrhea comprised 9.5% of endometrioma cases and had less advanced rASRM stage, were older at surgery, and had a higher probability of bilateral than unilateral endometrioma than patients with dysmenorrhea.

2.
Eur J Obstet Gynecol Reprod Biol ; 294: 217-221, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38301500

RESUMO

OBJECTIVE: Recent studies have suggested that endometriosis could be the result of excessive activation of signal transducer and activator of transcription 3 (STAT3), which is associated with the regulation of essential cellular mechanisms such as proliferation, invasion, and apoptosis. That finding implies that regulating STAT3 activation could play a key role in treating endometriosis. In the present study, we aimed to evaluate whether the anti-endometriotic effects of dienogest is mediated by the regulation of STAT3 activation. STUDY DESIGN: STAT3 activation was evaluated in normal endometrial and ovarian endometriotic tissues obtained from patients with/without preoperative dienogest treatment. A subsequent in vitro analysis with endometriotic cyst stromal cells (ECSCs) was used to confirm the direct influence of dienogest in STAT3 activation. RESULT: STAT3 activation is significantly higher in endometriotic tissues from non-treated patients than in normal endometrial tissues, and that difference is reversed by preoperative administration of dienogest. Similarly, the inhibitory effects of dienogest on STAT3 activation are demonstrated by in vitro results showing that dienogest treatment significantly inhibits IL-6-stimulated STAT3 activation in cultured ECSCs. That inhibition was accompanied by decreased expression of proliferative (PCNA), invasive (MMP-2), and anti-apoptotic (BCL-2) proteins. Furthermore, downregulating STAT3 activity with siRNA decreased PCNA, MMP-2, and BCL-2 expression in IL-6-treated ECSCs. CONCLUSION: Dienogest inhibits STAT3 activation in ECSCs, which affects their proliferation, invasiveness, and apoptosis.


Assuntos
Endometriose , Nandrolona/análogos & derivados , Feminino , Humanos , Endometriose/genética , Metaloproteinase 2 da Matriz , Fator de Transcrição STAT3/metabolismo , Interleucina-6/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Antígeno Nuclear de Célula em Proliferação/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/farmacologia , Células Estromais/metabolismo , Endométrio/metabolismo
3.
Sci Rep ; 13(1): 15461, 2023 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-37726372

RESUMO

The effects of menopausal hormone therapy (MHT) on non-alcoholic fatty liver disease (NAFLD) were compared based on the route of estrogen administration. The study included 368 postmenopausal women who received MHT for 12 months. Patients were divided into transdermal (n = 75) and oral (n = 293) groups based on the estrogen route. Changes in the prevalence of NAFLD were compared between the two groups before and after 12 months of MHT. In addition, differences in the progression of NAFLD after MHT based on the dose of estrogen and type of progestogen were evaluated in the oral group. After MHT, the prevalence of NAFLD decreased from 24 to 17.3% in the transdermal group but increased from 25.3 to 29.4% in the oral group. Little or no change was found in clinical characteristics and laboratory tests in the transdermal group during MHT. However, serum levels of total cholesterol and low-density lipoprotein cholesterol decreased and triglycerides and high-density lipoprotein cholesterol increased significantly in the oral group. Furthermore, changes in the prevalence of NAFLD were not significantly different based on the dose of estrogen or type of progestogen. Our findings indicate that transdermal estrogen can be beneficial in terms of NAFLD progression.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Feminino , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Progestinas , Estrogênios , HDL-Colesterol , Menopausa
4.
J Korean Med Sci ; 38(37): e279, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37724492

RESUMO

BACKGROUND: This study analyzed common gynecologic problems among Korean patients younger than ten years. METHODS: We performed a retrospective analysis of medical records of patients younger than ten years who visited the Pediatric and Adolescent Gynecology Clinic at Samsung Medical Center between 1995 and 2020. RESULTS: Among the 6,605 patients who visited the Pediatric and Adolescent Gynecology Clinic, data from 642 patients younger than ten years were analyzed in this study. The most common chief complaint was genital anomalies, followed by increased vaginal discharge and abnormal findings on clinical examinations. The most common disease entity was agglutination of the labia minora, which was commonly discovered incidentally during routine screenings. Vulvovaginitis, the second most common disease, was identified by symptoms of vaginal discharge, pruritus, and vaginal spotting. Neoplasm, issues with vaginal bleeding, and "other causes" were additional categories of gynecologic problems. 245 patients (38.2%) were referred from primary care sources, 175 patients (27.4%) sought care directly at the clinic, 169 patients (26.3%) were referrals from the institution's pediatric department, and the remainder were referrals from other departments. CONCLUSION: This study provides information about the gynecologic problems most frequently encountered in pediatric patients. The study provides helpful insight for primary care physicians into the proper management and timing of referrals for these gynecologic problems of pediatric patients.


Assuntos
Instituições de Assistência Ambulatorial , Doenças dos Genitais Femininos , Descarga Vaginal , Adolescente , Criança , Feminino , Humanos , Povo Asiático , República da Coreia/epidemiologia , Estudos Retrospectivos , Hemorragia Uterina , Descarga Vaginal/etiologia , Doenças dos Genitais Femininos/diagnóstico , Doenças dos Genitais Femininos/epidemiologia
5.
Front Endocrinol (Lausanne) ; 14: 1191096, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37361519

RESUMO

Objective: This study was conducted to assess the current status of emergency contraception (EC) use in reproductive-aged Korean women. Materials and methods: This study utilized a population-based, cross-sectional online survey using a self-completed questionnaire in women aged 20-44 years who had visited a clinic in the previous six months for contraception counseling. Reason for use, anxiety, and counseling for further contraception at EC use were analyzed according to age, history of childbirth, and contraceptive failure in EC users. Results: Among 1,011 respondents, 461 (45.6%) had experience with EC use. Younger age, need for EC due to inadequate contraception, and high anxiety were highly prevalent among EC users. However, women in the 20s were less likely to get counseling for further contraception at EC use. Additionally, the proportions of women who used EC due to inadequate contraception during sexual intercourse and who experienced high anxiety were lower among women who had a history of childbirth. Women who had a history of contraceptive failure worried less about EC use. Conclusion: Our findings offer insight for developing and improving individualized strategies for appropriate contraception, especially in young Korean EC users.


Assuntos
Anticoncepção Pós-Coito , Gravidez , Humanos , Feminino , Adulto , Estudos Transversais , Inquéritos e Questionários , Coito , República da Coreia/epidemiologia
6.
Breast Cancer Res Treat ; 198(2): 231-237, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36781519

RESUMO

PURPOSE: Although different gonadotropin-releasing hormone (GnRH) agonists may have different effects, their effect of ovarian protection during chemotherapy for breast cancer has not been compared. This study aimed to compare the effects of goserelin and leuprorelin for ovarian protection during chemotherapy in young patients with breast cancer. METHODS: This prospective study analyzed 193 patients with breast cancer aged ≤ 40 years who had regular menstruation and serum anti-Müllerian hormone (AMH) levels ≥ 1 ng/mL before treatment. Patients received either goserelin or leuprorelin for ovarian protection during doxorubicin/cyclophosphamide-based chemotherapy. Resumption of menstruation and changes in serum levels of AMH were compared between the two groups at 12 months after completion of chemotherapy. RESULTS: The mean age and the pretreatment serum AMH level were 33.2 years and 4.4 ng/mL in goserelin group and 34.2 years and 4.0 ng/mL in leuprorelin group. The proportion of patients who resumed menstruation was not different between the goserelin (94.4%) and leuprorelin (95.3%) groups at 12 months after chemotherapy completion. Serum AMH levels decreased significantly in both the goserelin (from 4.4 to 1.2 ng/mL) and leuprorelin (from 4.0 to 1.2 ng/mL) groups, with no statistical significance. In addition, no difference was found in the proportion of patients with serum AMH levels ≥ 1 ng/mL between the goserelin (49.5%) and leuprorelin (44.2%) groups at 12 months after chemotherapy. CONCLUSION: Goserelin and leuprorelin were comparable in terms of ovarian protection during doxorubicin/cyclophosphamide-based chemotherapy in young patients with breast cancer.


Assuntos
Neoplasias da Mama , Hormônios Peptídicos , Feminino , Humanos , Gosserrelina/efeitos adversos , Leuprolida/uso terapêutico , Estudos Prospectivos , Ciclofosfamida/efeitos adversos , Doxorrubicina/efeitos adversos
7.
Sci Rep ; 12(1): 21778, 2022 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-36526695

RESUMO

This nationwide population-based cohort study searched for demographic, comorbid, behavioral, and reproductive risk factors for idiopathic macular hole (MH) development using data provided by the Korean National Health Insurance Service. A total of 4,496,867 individuals aged 50-79 years who participated in the Korean National Health Screening Program in 2013 or 2014 were included. Participants were followed up until December 2018, and incident cases of idiopathic MH were identified. Prospective associations between incident idiopathic MH and various covariates were investigated using multivariable-adjusted Cox proportional hazard models. During an average follow-up period of 4.91 years, 3054 patients were newly diagnosed with idiopathic MHs. Women showed greater risk (hazard ratio of 1.71) and earlier presentation of idiopathic MH than men. Compared to the normal body mass index group, the obese group (≥ 25 kg/m2) showed a significantly lower risk of idiopathic MH. Among postmenopausal women, those with two or more children showed a greater risk of idiopathic MH than those who had not been pregnant, with a hazard ratio of 1.80. In conclusion, idiopathic MH occurred earlier and greater in women. Childbirth were associated with an increased risk of MH development, and obesity was associated with a lower risk of MH.


Assuntos
Perfurações Retinianas , Masculino , Criança , Humanos , Feminino , Perfurações Retinianas/cirurgia , Vitrectomia , Estudos de Coortes , Fatores de Risco , Obesidade/complicações , Obesidade/epidemiologia , Estudos Retrospectivos , Tomografia de Coerência Óptica
8.
Yonsei Med J ; 63(11): 999-1006, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36303308

RESUMO

PURPOSE: This study aimed to investigate the perceptions and behaviors of Korean women of reproductive age in regards to contraception counseling. MATERIALS AND METHODS: The study sample was collected in Korea and comprised 1011 women aged 20-44 years and 150 obstetrics and gynecology (OB/GYN) doctors. Participants completed online questionnaires assessing their current methods of contraception, knowledge of and satisfaction with contraceptive methods, and willingness to learn about and use other contraceptive methods. RESULTS: Women used condoms (74.2%), natural methods (cycle control or withdrawal, 52.4%), and combined oral contraceptives (COCs) (36.9%) more frequently than long-acting reversible contraception (LARC) methods, such as hormone-releasing intrauterine system (IUS) (4.5%), copper-intrauterine devices (3.3%), and subdermal implants (1.4%). Although the proportion of women who used LARC was low, those who used hormone-releasing IUS or subdermal implants reported high levels of satisfaction. The findings revealed discordant results between women and OB/GYN doctors regarding the initiation and quality of information provided by doctors about contraception and overall satisfaction with counseling. Most women (83.1%) expressed a desire to have more information about various contraceptive methods. More than 60% of women reported a willingness to use LARC, such as hormone-releasing IUS or subdermal implants, when provided with detailed information in counseling. CONCLUSION: The majority of Korean women are familiar with condoms and natural methods, but lack knowledge about alternative contraceptive methods, including LARC. Women who used LARC reported higher levels of satisfaction than those who used other methods.


Assuntos
Anticoncepcionais Femininos , Ginecologia , Gravidez , Feminino , Humanos , Anticoncepção/métodos , República da Coreia , Hormônios
9.
J Korean Med Sci ; 37(26): e207, 2022 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-35790209

RESUMO

BACKGROUND: There are several medical treatment options for endometrioma. Progestin, especially dienogest, is an effective drug for preventing recurrence of endometrioma after surgery. Additionally, oral contraceptive (OC) use after conservative surgery has been reported to reduce significantly the risk of endometrioma recurrence. The aim of this study was to compare the long-term effects of gonadotropin-releasing hormone (GnRH) agonist followed by OC to those of dienogest alone to prevent recurrence of endometrioma after laparoscopic surgery. METHODS: A retrospective cohort study was performed on patients who underwent conservative laparoscopic surgery for endometrioma between January 2000 and December 2020, in the Endometriosis Clinic, Department of Gynecology, Samsung Medical Center. A total of 624 patients who received medical treatment at least six months after laparoscopic conservative surgery for endometrioma was included. Among them, 372 patients used OC after GnRH agonist therapy, and 252 patients used dienogest. Within the OC group, 148 used a 21/7 regiment and 224 used a 24/4 regimen. A cumulative endometrioma recurrence curve was presented using the Kaplan-Meier method to compare the recurrence of those groups. RESULTS: The cumulative recurrence rate of endometrioma for 60 months was 2.08% (n = 4) in the OC after GnRH agonist group and 0.40% (n = 1) in the dienogest group. There was no statistical difference in cumulative recurrence of endometrioma between the two groups. In subgroup analysis, the cumulative recurrence rate of endometrioma over 60 months was 4.21% (n = 2) in the 21/7 OC group and 1.09% (n = 2) in the 24/4 OC group and showed no significant difference. CONCLUSION: Long-term use of OC after GnRH agonist as well as that of dienogest treatment are effective postoperative medical therapies for preventing endometrioma recurrence. Thus, the choice of regimen can be individualized or used interchangeably depending on patient condition, need for contraception, and compliance with drug therapy.


Assuntos
Endometriose , Anticoncepção , Anticoncepcionais Orais/uso terapêutico , Endometriose/tratamento farmacológico , Endometriose/prevenção & controle , Endometriose/cirurgia , Feminino , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Nandrolona/análogos & derivados , Estudos Retrospectivos , Prevenção Secundária/métodos
10.
Sci Rep ; 12(1): 6068, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35414644

RESUMO

This nationwide population-based cohort study evaluated the association between female reproductive factors and the incidence of retinal vein occlusion (RVO) and retinal artery occlusion (RAO) using data provided by the Korea National Health Insurance Service. A total of 2,289,347 postmenopausal women over 50 years of age who participated in both national health screening and cancer screening in 2013 or 2014 were included. Data on female reproductive factors, including age at menarche, age at menopause, parity, history of hormone replacement therapy, and oral contraceptive pill usage, were collected. Patients were followed up until December 2018, and incident cases of RVO and RAO were identified using registered diagnostic codes from claim data. During an average follow-up period of 4.90 years, 7461 and 1603 patients were newly diagnosed with RVO and RAO, respectively. In the multivariable-adjusted Cox proportional hazard model, patients who experienced menopause after 55 years of age had a lower risk of RVO and RAO development compared to those who had menopause before 45 years of age, with a hazard ratio (95% confidence interval) of 0.83 (0.76-0.95) for RVO and 0.80 (0.66‒0.98) for RAO. In conclusion, early menopause was an independent risk factor for future development of RVO and RAO.


Assuntos
Oclusão da Artéria Retiniana , Doenças Retinianas , Oclusão da Veia Retiniana , Estudos de Coortes , Feminino , Humanos , Incidência , Menopausa , Pessoa de Meia-Idade , Gravidez , Oclusão da Artéria Retiniana/diagnóstico , Doenças Retinianas/complicações , Oclusão da Veia Retiniana/etiologia , Estudos Retrospectivos , Fatores de Risco
11.
Mol Hum Reprod ; 28(4)2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35333355

RESUMO

The NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome is a cytosolic multi-protein complex that induces inflammation and is known to be regulated negatively by autophagy. Previous studies reported an abnormal induction of autophagy linked to progesterone resistance in human endometriotic cells. Therefore, an aberrant autophagy induction response to progesterone might contribute to the altered inflammatory response observed in endometriotic tissues. To evaluate this hypothesis, we elucidate whether regulation of the NLRP3 inflammasome by ovarian steroids is mediated by autophagy in human endometrial stromal cells (normal endometrial stromal cells (NESCs)) from patients with uterine leiomyoma (presumed normal) and whether abnormal autophagy induction in endometriotic cyst stromal cells (ECSCs) affects NLRP3 inflammasome-induced interleukin-1ß (IL-1ß) production. Our results show that estrogen enhanced NLRP3 inflammasome activation in NESCs, resulting in increased IL-1ß production. Progesterone decreased NLRP3 inflammasome activity with an increase in autophagy induction in estrogen-treated NESCs. Inhibition of NLRP3 inflammasome activity by progesterone was blocked by autophagy inhibition. However, progesterone failed to change NLRP3 inflammasome activity and autophagy induction in estrogen-treated ECSCs. In contrast, dienogest, a specific progesterone receptor agonist, reduced NLRP3 inflammasome-mediated IL-1ß production through autophagy induction in ECSCs. Furthermore, autophagy induction was decreased and NLRP3 inflammasome activity was increased in endometriotic tissues, which was reversed by preoperative administration of dienogest. In conclusion, our results suggest that progesterone inhibits NLRP3 inflammasome activation through autophagy in endometrial stromal cells. However, this inhibitory effect is attenuated in endometriotic stromal cells due to an aberrant autophagic response to progesterone, which could lead to an altered inflammatory response in endometriosis.


Assuntos
Cistos , Endometriose , Autofagia , Endometriose/genética , Feminino , Humanos , Inflamassomos/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Progesterona/farmacologia , Células Estromais
12.
Front Endocrinol (Lausanne) ; 12: 708931, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744997

RESUMO

Objective: This study aimed to determine the most appropriate age for height control treatment in patients with Marfan syndrome (MFS). Materials and Methods: This retrospective study included patients with MFS who underwent height control treatment with estradiol valerate. The estrogen dose was increased according to the height change. The cut-off age for the maximum difference between the expected height and actual final height was evaluated. Results: Seventeen patients were included in this study. The difference between the height predicted by the growth curve and the final height (gcHtD) and that predicted by the bone age and the final height (baHtD) was the largest in the 10.5 years age group (p=0.0045 and p=0.0237, respectively). The gcHtD was 10.6 (10.2, 13.5) cm for patients aged ≤10.5 years, whereas it was 0.6 (-3.65, 5.85) cm for patients aged >10.5 years. The baHtD was 10.1 (7.31, 11.42) cm for patients aged ≤10.5 years, while it was 3.83 (0.84, 6.4) cm for patients aged >10.5 years. When height change was observed for a minimum of 6 months after completion of estrogen treatment, the average growth was 0.6 (0.2, 2.1) cm. Conclusion: Initiating height control treatment before the age of 10.5 years is effective in female patients with MFS.


Assuntos
Estatura/efeitos dos fármacos , Estradiol/administração & dosagem , Estrogênios/administração & dosagem , Síndrome de Marfan/tratamento farmacológico , Fatores Etários , Criança , Feminino , Seguimentos , Humanos , Síndrome de Marfan/patologia , Prognóstico , Estudos Retrospectivos
13.
Front Endocrinol (Lausanne) ; 12: 649952, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33776942

RESUMO

Background: Hip structural analysis (HSA) is a method for evaluating bone geometry reflecting bone structural and biomechanical properties. However, tissue-selective estrogen complex (TSEC) treatment effects on HSA have not been investigated. Objective: This study was performed to evaluate the effect of TSEC treatment on hip geometry in postmenopausal Korean women. The treatment was given for 12 months, and hip geometry was measured by HSA. Materials and Methods: A total of 40 postmenopausal women who received TSEC containing conjugated estrogen 0.45 mg and bazedoxifene 20 mg for treating vasomotor symptoms were included in this retrospective cohort study. The changes in bone mineral density and parameters of HSA including the outer diameter, cross-sectional area, cross-sectional moment of inertia, cortical thickness, section modulus, and buckling ratio as determined by dual-energy X-ray absorptiometry were compared before and after 12 months of TSEC treatment. Results: Mean age and years since menopause were 55.1 and 4.5 years, respectively. Total hip bone mineral density significantly increased by 0.74% after treatment (P=0.011). The changes in HSA were mainly demonstrated in the narrow femoral neck: cross-sectional area (P=0.003) and cortical thickness (P<0.001) increased significantly. For the shaft region, only SM decreased significantly after treatment (P=0.009). However, most parameters did not change significantly with TSEC treatment in the intertrochanteric and shaft regions. Conclusions: Our findings demonstrate that 12 months of TSEC treatment could improve bone geometry as measured by HSA. The findings suggest that TSEC might be an interesting option for the prevention of fracture as well as osteoporosis in postmenopausal women.


Assuntos
Estrogênios/administração & dosagem , Colo do Fêmur/efeitos dos fármacos , Fraturas do Quadril/prevenção & controle , Indóis/administração & dosagem , Osteoporose Pós-Menopausa/tratamento farmacológico , Pós-Menopausa , Absorciometria de Fóton/métodos , Fenômenos Biomecânicos , Densidade Óssea/efeitos dos fármacos , Feminino , Fêmur , Quadril/fisiologia , Humanos , Menopausa , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/sangue , República da Coreia , Estudos Retrospectivos
14.
Sci Rep ; 11(1): 3585, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33574350

RESUMO

This study was performed to evaluate serum estradiol level in postmenopausal women using oral menopausal hormone therapy (MHT) with different doses and formulations of estrogens. A total of 344 postmenopausal women who received oral MHT was included in this cross-sectional study. Serum estradiol level was compared according to formulation (estradiol hemihydrate [EH] or valerate [EV], conjugated estrogen [CE]) and dose (estradiol 1 or 2 mg, CE 0.45 or 0.625 mg) of the estrogens. Mean age and years since menopause were 56.9 and 7.9 years, respectively. Mean duration of MHT was 27.4 months. Since serum estradiol levels were not significantly different at either dose, EH and EV at the same dose were combined for comparisons: estradiol 1 mg and 2 mg. The serum estradiol level with estradiol 2 mg (107.6 pg/mL) was significantly higher by 60% than with estradiol 1 mg (65.8 pg/mL) or CE 0.45 mg (60.1 pg/mL), and it was also significantly higher than with CE 0.625 mg (76.8 pg/mL). Our findings suggest that serum estradiol level is not directly proportional to estrogen dose. In terms of serum concentration, CE 0.45 mg is equivalent to estradiol 1 mg.


Assuntos
Estradiol/sangue , Estrogênios/sangue , Menopausa/sangue , Pós-Menopausa/sangue , Relação Dose-Resposta a Droga , Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios , Estrogênios/administração & dosagem , Estrogênios/metabolismo , Feminino , Terapia de Reposição Hormonal , Humanos , Menopausa/efeitos dos fármacos , Pessoa de Meia-Idade , Pós-Menopausa/efeitos dos fármacos
15.
Mol Hum Reprod ; 27(2)2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33507306

RESUMO

Endoplasmic reticulum (ER) stress serves as a key modulator of the inflammatory response by controlling nuclear factor-kappaB (NF-κB) signaling. Previous studies from our laboratory have reported an abnormal induction of ER stress linked to progesterone resistance in human endometriotic cells. Therefore, an aberrant ER stress response to progesterone might contribute to the altered inflammatory response observed in endometriotic tissues. To evaluate this hypothesis, we investigated whether ER stress is involved in regulation of NF-κB in endometrial stromal cells and whether induction of aberrant ER stress in endometriotic stromal cells affects pro-inflammatory cytokine production. We found that tunicamycin-induced ER stress inhibited NF-κB activation and pro-inflammatory cytokine (IL-6 and COX2) production in TNF-α- or IL-1ß-treated normal endometrial stromal cells (NECSs). Tunicamycin increased the expression of A20 and C/EBPß, which are negative regulators of NF-κB, and this increase inhibited NF-κB activity in NESCs incubated with TNF-α or IL-1ß. Similarly, progesterone increased A20 and C/EBPß expression through upregulation of ER stress in NESCs, resulting in inhibition of NF-κB activity and IL-6 and COX2 production. However, progesterone had no significant effects on induction of ER stress, A20 or C/EBPß expression, NF-κB activity or IL-6 or COX2 production in ovarian endometriotic cyst stromal cells (ECSCs). In contrast, upregulation of ER stress by tunicamycin significantly reduced IL-6 and COX2 production by inhibiting NF-κB activity in ECSCs. In conclusion, our results suggest that NF-κB activity in endometriotic stromal cells was not inhibited because of an aberrant ER stress response to progesterone, resulting in an increase in pro-inflammatory cytokine production.


Assuntos
Endometriose/metabolismo , Endométrio/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , NF-kappa B/metabolismo , Progesterona/farmacologia , Células Estromais/efeitos dos fármacos , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Estudos de Casos e Controles , Células Cultivadas , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Endometriose/patologia , Endométrio/metabolismo , Endométrio/patologia , Chaperona BiP do Retículo Endoplasmático , Feminino , Proteínas de Choque Térmico/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Transdução de Sinais , Células Estromais/metabolismo , Células Estromais/patologia , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo
16.
Reprod Sci ; 28(5): 1556-1562, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33449347

RESUMO

The aim of this study was to evaluate the changing pattern of bone mineral density (BMD) levels after 3 years of dienogest use post endometrioma surgery and investigate the possible predictive factors for BMD reduction. This retrospective study included 44 reproductive-aged women who took dienogest (2 mg/day) and followed up BMD for 3 years after laparoscopic endometrioma surgery from July 2013 to December 2018. In addition, to investigate the predictive factors in the group with decreased BMD, analysis was added for patients with decreased BMD after taking dienogest for 1 year post laparoscopic endometrioma surgery. After 3 years of treatment with dienogest, BMD of both the lumbar spine (- 4.4%) and femur neck (- 3.6%) decreased significantly compared to the baseline levels. Bone loss predominantly occurred during the first year of treatment in the lumbar spine (- 2.4%) and gradually decreased with time during the treatment period. The predictive factors for BMD reduction after dienogest use were evaluated based on a 1-year change in BMD levels of 160 women, but no associated factors were found. This study demonstrated that dienogest use for 3 years was associated with a significant and gradual decrease in BMD and no predictive factors for BMD reduction during the first year of treatment with dienogest were found. These results may be useful in counseling patients regarding long-term effects of dienogest use on reducing BMD levels so that appropriate preventive measures can be taken.


Assuntos
Densidade Óssea/efeitos dos fármacos , Endometriose/cirurgia , Nandrolona/análogos & derivados , Adulto , Feminino , Humanos , Nandrolona/uso terapêutico , Complicações Pós-Operatórias , Estudos Retrospectivos
17.
Breast Cancer Res Treat ; 179(1): 125-130, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31541382

RESUMO

PURPOSE: This study evaluated the factors associated with endometrial pathologies during tamoxifen use in women with breast cancer. METHODS: This study analyzed 821 endometrial biopsies from women who received tamoxifen for breast cancer. Clinical characteristics were compared according to the presence of endometrial pathology (atypical hyperplasia and cancer). In addition, patients with endometrial polyps were compared with women with normal histology. RESULTS: Among 821 biopsies, atypical endometrial hyperplasia and cancer were diagnosed in 7 women each. Endometrial polyps were found in 173 women, and 634 women presented normal histology. In comparing women with endometrial pathology (atypical hyperplasia and cancer, n = 14) and those without pathology, parity was significantly lower (P = 0.014) and endometrial thickness was significantly higher (P < 0.001) in women with pathology. In addition, abnormal uterine bleeding was more common in the pathology group (P < 0.001). However, age, body mass index, menopausal status, intrauterine device use, history of diabetes mellitus, and duration of tamoxifen use did not differ according to the presence of pathology. In comparing women with endometrial polyps and those with normal endometrium, significant differences were found in parity (P < 0.001), duration of tamoxifen use (P = 0.003), and endometrial thickness (P < 0.001), but not in the presence of abnormal vaginal bleeding. CONCLUSION: Parity, endometrial thickness, and the presence of abnormal vaginal bleeding, but not age, body mass index, and menopausal status, may be associated with endometrial pathology during tamoxifen use in women with breast cancer. This finding might provide useful information for gynecological surveillance and counseling during tamoxifen treatment.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Endométrio/patologia , Tamoxifeno/administração & dosagem , Adulto , Antineoplásicos Hormonais/efeitos adversos , Biópsia , Estudos de Casos e Controles , Hiperplasia Endometrial/induzido quimicamente , Hiperplasia Endometrial/epidemiologia , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/induzido quimicamente , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/patologia , Endométrio/efeitos dos fármacos , Feminino , Humanos , Pessoa de Meia-Idade , Pólipos/química , Pólipos/epidemiologia , Pólipos/patologia , Estudos Retrospectivos , Tamoxifeno/efeitos adversos , Resultado do Tratamento
18.
Mol Hum Reprod ; 26(1): 30-39, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31814016

RESUMO

Dienogest, a specific progesterone receptor agonist, is used in the treatment of endometriosis. However, it is still unclear as to the mechanisms of therapeutic effects on endometriosis. Our recent study showed that endometriosis may be the result of aberrant endoplasmic reticulum (ER) stress induction due to progesterone resistance. This finding suggests that the regulation of ER stress induction may play a key role in treatment of endometriosis. Therefore, the anti-endometriotic effects of dienogest may be mediated by regulation of ER stress. To test this hypothesis, we elucidate whether dienogest affects endometriotic stromal cell apoptosis, proliferation and invasiveness by modulating ER stress-induced CCAAT/enhancer-binding protein homologous protein (CHOP) expression. Specifically, PRKR-like ER kinase (PERK)/eukaryotic initiation factor 2α (eIF2α)/activating transcription factor 4 (ATF4), inositol-requiring kinase 1 (IRE1)/TNF receptor-associated factor 2 (TRAF2)/apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal kinase (JNK) signaling, and downstream CHOP were evaluated to determine the involved ER stress-mediated regulation mechanism of CHOP expression. Our results show that progesterone treatment did not have any significant effects on ER stress, apoptosis, proliferation, and invasion in estrogen-treated endometriotic cyst stromal cells (ECSCs). However, dienogest treatment upregulated the induction of ER stress. It also led to increased apoptosis, and decreased proliferation and invasiveness. These dienogest-induced changes in apoptosis, proliferation and invasiveness were reversed by the ER stress inhibitor salubrinal. Furthermore, dienogest-induced ER stress increased CHOP expression through activation of both PERK/elf2α/ATF4 and IRE1/TRAF2/ASK1/JNK signaling. This upregulation was blocked by transfection with PERK and IRE1 siRNA, which decreased apoptosis and increased the proliferation and invasiveness of dienogest-treated ECSCs. Taken together, our findings indicate that dienogest enhances ER stress induction in endometriotic stromal cells, which affects apoptosis, proliferation and invasiveness via CHOP upregulation.


Assuntos
Cistos/tratamento farmacológico , Endometriose/tratamento farmacológico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Antagonistas de Hormônios/farmacologia , Nandrolona/análogos & derivados , Fator de Transcrição CHOP/genética , eIF-2 Quinase/genética , Fator 4 Ativador da Transcrição/genética , Fator 4 Ativador da Transcrição/metabolismo , Adulto , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cistos/genética , Cistos/metabolismo , Cistos/patologia , Endometriose/genética , Endometriose/metabolismo , Endometriose/patologia , Endométrio/efeitos dos fármacos , Endométrio/metabolismo , Endométrio/patologia , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Endorribonucleases/antagonistas & inibidores , Endorribonucleases/genética , Endorribonucleases/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , MAP Quinase Quinase Quinase 5/genética , MAP Quinase Quinase Quinase 5/metabolismo , Sistema de Sinalização das MAP Quinases , Nandrolona/farmacologia , Progesterona/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Células Estromais/patologia , Fator 2 Associado a Receptor de TNF/genética , Fator 2 Associado a Receptor de TNF/metabolismo , Fator de Transcrição CHOP/agonistas , Fator de Transcrição CHOP/metabolismo , eIF-2 Quinase/antagonistas & inibidores , eIF-2 Quinase/metabolismo
19.
J Menopausal Med ; 25(1): 49-54, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31080789

RESUMO

OBJECTIVES: Inflammation is a major mechanism underlying coronary heart disease (CHD) and C-reactive protein (CRP) is a marker of inflammation. When administered soon after menopause, menopausal hormone therapy (MHT) prevents CHD. This study was conducted to examine the impact of estrogen by administration route on CRP in postmenopausal Korean women using micronized progesterone (MP4) for endometrial protection. METHODS: This retrospective cohort study included 129 healthy women without CHD risk factors. Eighty-nine women took oral estrogen (conjugated equine estrogen, 0.625 mg/day or equivalent), and 40 women applied a 1.5-mg/day 0.1% percutaneous estradiol gel. MP4 was added in 82 women with an intact uterus. The CRP level was measured at baseline and three and six months after initiation of MHT. RESULTS: The baseline characteristics were comparable between the MHT groups except current age and age at menopause. After controlling for age, menopausal age, body mass index, and basal CRP, no significant change in CRP was observed in the oral estrogen group (n = 29). Follow-up CRP levels were also similar to the baseline in the percutaneous estrogen group (n = 18). However, three-month CRP was significantly lower than six-month CRP, and there was a significant time trend within the percutaneous estrogen group. However, the group difference did not reach statistical significance. CRP also did not differ by addition of MP4 in either group. CONCLUSIONS: In postmenopausal Korean women, no change in CRP was observed with oral estrogen, while percutaneous estrogen might decrease CRP. The estrogenic impacts were not influenced by adding MP4.

20.
J Pediatr Adolesc Gynecol ; 32(5): 530-534, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31145987

RESUMO

STUDY OBJECTIVE: To evaluate the efficacy of long-term estrogen replacement therapy (ERT) in uterine development and bone mineral density (BMD) of Turner syndrome (TS) women with premature ovarian insufficiency (POI). DESIGN AND SETTING: Retrospective study. PARTICIPANTS AND INTERVENTIONS: Thirty-seven TS women grouped according to ovarian function status: TS women with POI (n = 32), aged 11-26 years, and those with intact ovarian function (IOF; n = 5), aged 13-17 years. TS women with POI underwent ERT. MAIN OUTCOME MEASURES: Changes in uterine length, anterior-posterior (AP) fundal diameter of the uterus, and BMD were assessed. Statistical methods included Mann-Whitney U test and paired t test. RESULTS: In TS women with POI, uterine length, AP fundal diameter, and BMD significantly increased after ERT (P < .001). TS women with POI were subdivided into classic (n = 11) and variant (n = 21) types, and there were no significant differences in uterine development and BMD according to types of chromosome. After receiving ERT, AP fundal diameter was significantly longer in classic TS women (P = .034) compared with those with variant type. CONCLUSION: Long-term ERT increased uterine length (before: 4.4 cm; after: 7.2 cm) and AP fundal diameter (before: 0.9 cm; after: 2.4 cm), and improved BMD in TS women with POI. After ERT, in TS women with POI, uterine length, BMD at lumbar 2-4 and femoral neck were similar to those of TS women with IOF. Therefore, TS women with POI can catch up to those with IOF by receiving ERT.


Assuntos
Terapia de Reposição de Estrogênios/métodos , Estrogênios/uso terapêutico , Insuficiência Ovariana Primária/tratamento farmacológico , Síndrome de Turner/tratamento farmacológico , Adolescente , Adulto , Densidade Óssea/efeitos dos fármacos , Estudos de Casos e Controles , Criança , Estrogênios/farmacologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Útero/efeitos dos fármacos , Útero/crescimento & desenvolvimento , Adulto Jovem
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