Modulation of Bone Mineral Density and Its Response to Menopausal Hormone Therapy according to the Apolipoprotein E Genotype in Postmenopausal Korean Women.

OBJECTIVES: Genetic factors are a major cause of osteoporosis. The present study evaluated the association of the apolipoprotein E (ApoE) genotype with bone mineral density (BMD) and its response to menopausal hormone therapy (MHT) in postmenopausal Korean women. METHODS: This retrospective cohort study included 172 postmenopausal women with no endocrine diseases, medications, or lifestyles that would affect bone metabolism and who were continuously treated with MHT for at least 2 years. BMDs were measured at baseline and periodically. RESULTS: Linear regression analysis demonstrated similar baseline BMDs at the lumbar spine, but significantly lower at the femur neck and total hip in the ApoE ε4 carrier than in the noncarrier group, after controlling for age, body mass index, and history of MHT usage. Overall, the Wilcoxon signed rank test demonstrated that MHT increased the BMD percentage change at all three regions, and the Generalized Estimating Equation (GEE) demonstrated significant time trends at the lumbar spine and femur neck. ApoE ε4 noncarriers exhibited a significant time trend in BMD changes at the femur neck, whereas ε4 carriers exhibited a time trend at the lumbar spine. However, BMD changes at each time point were comparable at all regions between the groups. Notably, GEE adjusted for baseline characteristics and BMD revealed a significant interaction effect of time and ApoE ε4 allele in BMD changes at the femur neck. CONCLUSIONS: Postmenopausal Korean women carrying the ApoE ε4 allele demonstrated a lower hip BMD compared with ε4 noncarriers. Furthermore, the ε4 allele may modulate hip BMD responses to MHT.

Effects of Combination Oral Contraceptives on Bone Mineral Density and Metabolism in Perimenopausal Korean Women.

OBJECTIVES: A retrospective cohort study was conducted to evaluate the effects of combination oral contraceptives (COCs) on bone mineral density (BMD) and metabolism in perimenopausal Korean women. METHODS: The study subjects comprised two groups. The COC group included 55 women who took low-dose COC for at least one year to control vasomotor symptoms. Another 55 women who had annual checkups without history of COC use served as controls. BMD and bone turnover markers were assessed periodically. RESULTS: In the control group, 12-month BMD values at the lumbar spine (LS) and total hip (TH) significantly decreased with a greater magnitude at LS, and bone resorption (BR) and formation (BF) markers increased concurrently with a larger change in BR. COCs increased BMD at LS after 12 months and prevented BMD decline at TH. Multivariable linear regression revealed a significant difference in LS BMD between groups at 12 months. In the COC group, there were significant negative correlations between baseline BMD and Z-score at LS and corresponding changes at 12 months. COCs did not alter BR markers, whereas BF markers were significantly decreased at 3 months. Group comparison at 12 months, as tested with adjusted linear regression, disclosed significant differences in both BR and BF makers. CONCLUSIONS: Bone loss associated with activated bone turnover is evident during the menopausal transition, and COCs might prevent BMD decrease and suppress bone turnover markers in perimenopausal Korean women. Significant increase in LS BMD and decreases in BF makers suggest underlying mechanisms of greater impact on BF.

Effects of menopausal hormone therapy on ambulatory blood pressure and arterial stiffness in postmenopausal Korean women with grade 1 hypertension: a randomized, placebo-controlled trial.

BACKGROUND: Estrogen therapy in early menopausal women decreases the risk of coronary heart disease and parenteral, but not oral, estrogen is reported to reduce blood pressure (BP). Progestogens are typically added to estrogens to prevent unopposed endometrial stimulation. The effects of progestogen on BP have been less well studied to date. This study was conducted to explore the impacts of micronized progesterone (MP4) combined with percutaneous estradiol gel (PEG) on hemodynamics in postmenopausal Korean women with grade 1 hypertension. METHODS: Fifty-two postmenopausal women (aged 49-75 years) with systolic BP (SBP) of 140-160 mmHg or diastolic BP (DBP) of 90-100 mmHg were randomly assigned for 12 weeks to placebo (n = 16), estrogen therapy (ET) (n = 19) with PEG (0.1 %, 1 g./d), or estrogen + progestogen therapy (EPT, n = 17) with PEG and MP4 (100 mg/d). The primary endpoint was ambulatory BP and the secondary endpoints were arterial stiffness as brachial-ankle pulse-wave velocity (baPWV) and aortic parameters on applanation tonometry. RESULTS: One woman in the ET group dropped out, so 51 participants were finally analyzed. Outcome measures for ambulatory BP and arterial stiffness were not different between groups. Within-group comparisons showed that EPT significantly decreased daytime heart rate and baPWV: the changes from baseline (mean ± standard deviation) were - 2.5 ± 5.7 bpm (P = 0.03) and - 0.6 ± 1.4 m/s (P = 0.04), respectively. After adjusting for baseline, linear regression analysis revealed a significant difference in the relationship between baseline and 12-week baPWV among groups (P = 0.02). The relationship was significantly different between placebo and ET (P = 0.03) and EPT (P = 0.01), respectively, but not between ET and EPT. Additionally, pooled results of active treatments disclosed that SBP, DBP, PWV, and augmentation index at the aorta were significantly reduced relative to baseline. CONCLUSIONS: There was no difference in ambulatory BP between ET and EPT in postmenopausal Korean women with grade 1 hypertension. Further, ET and EPT similarly decreased baPWV from baseline as compared with placebo. MP4 might not adversely influence estrogen effects on ambulatory BP and arterial stiffness. TRIAL REGISTRATION: Clinical Research Information Registry, KCT0005405, Registered 22 September 2020 - Retrospectively registered, https://cris.nih.go.kr/cris/search/detailSearch.do?all_type=Y&search_page=L&pageSize=10&page=1&seq=17608&search_lang=E .

17ß-Estradiol Inhibits Lysophosphatidylcholine-Induced Apoptosis in Cultured Vascular Smooth Muscle Cells.

OBJECTIVES: Coronary heart disease (CHD) risk increases in women after menopause, but menopausal hormone therapy (MHT) helps prevent CHD if started early after menopause. To explore the mechanism underlying the direct vascular actions of estrogen, the effects of 17ß-estradiol (E2) on apoptosis of vascular smooth muscle cells (VSMCs) induced with lysophosphatidylcholine (lysoPC), an active component of oxidized low-density lipoprotein, were investigated in the present study. METHODS: VSMCs were isolated from rat aortas. Apoptosis and protein expression of caspases were assessed using propidium iodide staining and Western blot analysis, respectively. Intracellular formation of reactive oxygen species (ROS) was examined using dichlorofluorescein diacetate, a cell-permeable oxidation-sensitive probe, and quantitated with flow cytometry. Nuclear factor-κB (NF-κB) activation was determined after transfection with a reporter plasmid containing the luciferase reporter gene. RESULTS: After pre-treatment for 24 hours, 17ß-E2 suppressed lysoPC-induced (15 µM) apoptotic cell death in a dose-dependent manner with statistical significance at near physiological concentration. 17ß-E2 (10⁻6 M) also increased protein levels of caspase-9 and -8 precursors and decreased the active form of caspase-3. Western blot analysis using subcellular fractions showed that 17ß-E2 decreased mitochondrial Bax levels and concomitantly increased cytosolic Bax expression. Furthermore, intracellular production of ROS and NF-κB-mediated transcriptional activity were reduced with 17ß-E2. In addition, estrogen effects on apoptosis were partially blocked by ICI 182,780, a specific estrogen receptor antagonist. CONCLUSIONS: In cultured VSMCs treated with lysoPC, 17ß-E2 reduced apoptotic cell death by down-regulating both extrinsic and intrinsic apoptosis pathways, contributing to the preventive action of MHT against CHD.

Effects of 17ß-Estradiol on the Plasminogen Activator System in Vascular Smooth Muscle Cells Treated with Lysophophatidylcholine.

OBJECTIVES: When administered soon after menopause, hormone therapy can prevent coronary heart diseases in women. To explore the mechanism underlying the cardioprotective actions of estrogen, we investigated the effects of 17ß-estradiol (17ß-E2) on the plasminogen activator system using cultured vascular smooth muscle cells (VSMCs). METHODS: VSMCs were isolated from rat aortas. Protein expression of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were evaluated using Western blotting and enzyme-linked immunosorbent assay, respectively. The enzyme activity of PAI-1 in a conditioned medium was assessed via reverse fibrin overlay zymography and that of t-PA was assessed via fibrin overlay zymography. Gene expression was quantified using real-time reverse transcription-polymerase chain reaction. RESULTS: Following pre-treatment for 24 hours, 17ß-E2 suppressed both protein expression and enzyme activity of PAI-1 stimulated by lysophosphatidylcholine (lysoPC) in a significant and dose-dependent manner at a near physiological concentration. Moreover, 17ß-E2 (10⁻7 M) inhibited PAI-1 gene expression, and ICI 182,780-a specific estrogen receptor antagonist-blocked the effects of 17ß-E2 on the PAI-1 protein. 17ß-E2 did not affect t-PA secretion but significantly enhanced free t-PA activity through reduced binding to PAI-1. Furthermore, 17ß-E2 suppressed intracellular reactive oxygen species production and nuclear factor-κB-mediated transcription. CONCLUSIONS: In VSMCs stimulated with lysoPC, 17ß-E2 reduced PAI-1 expression through a non-receptor-mediated mechanism via antioxidant activity as well as a receptor-mediated mechanism; however, it did not alter t-PA secretion. Of note, 17ß-E2 suppressed PAI-1 activity and concurrently enhanced t-PA activity, suggesting a beneficial influence on fibrinolysis.

Indazole-Cl inhibits hypoxia-induced cyclooxygenase-2 expression in vascular smooth muscle cells.

Atherosclerosis is the most common root cause of arterial disease, such as coronary artery disease and carotid artery disease. Hypoxia is associated with the formation of macrophages and increased inflammation and is known to be present in lesions of atherosclerotic. Vascular smooth muscle cells (VSMCs) are one of the major components of blood vessels, and hypoxic conditions affect VSMC inflammation, proliferation and migration, which contribute to vascular stenosis and play a major role in the atherosclerotic process. Estrogen receptor (ER)-ß is thought to play an important role in preventing the inflammatory response in VSMCs. In this report, we studied the anti-inflammatory effect of indazole (In)-Cl, an ERß-specific agonist, under conditions of hypoxia. Expression of cyclooxygenase-2 reduced by hypoxia was inhibited by In-Cl treatment in VSMCs, and this effect was antagonized by an anti-estrogen compound. Additionally, the production of reactive oxygen species induced under conditions of hypoxia was reduced by treatment with In-Cl. Increased cell migration and invasion by hypoxia were also dramatically decreased following treatment with In-Cl. The increase in cell proliferation following treatment with platelet-derived growth factor was attenuated by In-Cl in VSMCs. RNA sequencing analysis was performed to identify changes in inflammation-related genes following In-Cl treatment in the hypoxic state. Our results suggest that ERß is a potential therapeutic target for the suppression of hypoxia-induced inflammation in VSMCs.

The Effects of Menopausal Hormone Therapy on Serum Level of C-reactive Protein in Postmenopausal Korean Women.

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.

The Efficacy of Long-Term Estrogen Replacement Therapy in Turner Syndrome Women with Premature Ovarian Insufficiency.

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.

Comparison of long-term use of combined oral contraceptive after gonadotropin-releasing hormone agonist plus add-back therapy versus dienogest to prevent recurrence of ovarian endometrioma after surgery.

OBJECTIVE: The aim of this study was to compare long-term use of combined oral contraceptive (COC) after gonadotropin-releasing hormone (GnRH) agonist plus add-back therapy with dienogest (DNG) treatment as medical treatments after surgery for ovarian endometrioma. METHODS: This prospective cohort study analyzed 52 reproductive-aged women who underwent surgery for ovarian endometrioma and received postoperative medical treatment with either COC after GnRH agonist (n = 20) or DNG (n = 32) for 24 months. Changes in quality-of-life (QOL) and bone mineral density (BMD) were compared according to treatment. In addition, recurrence of pain and lesions were compared. RESULTS: Baseline characteristics did not differ in demographic profiles and factors associated with endometriosis or QOL. During 24 months of treatment, no differences in any component of QOL were found between the two groups. BMD at the lumbar spine significantly decreased after the first 6 months of treatment in both COC after GnRH agonist (-3.5%) and DNG (-2.3%) groups, but the groups did not differ statistically. After 6 months, further decrease in BMD was not observed until 24 months in both groups. In addition, no cases of pain or endometrioma recurrence were found. CONCLUSION: Our results suggest that long-term use of COC after GnRH agonist plus add-back therapy is comparable to dienogest as a long-term postoperative medical treatment for endometriosis.

Effects of Adding Intravenous Pamidronate to Ongoing Menopausal Hormone Therapy in Postmenopausal Korean Women with Low Bone Mineral Density.

OBJECTIVES: We evaluated the effects of adding intravenous pamidronate to ongoing menopausal hormone therapy (MHT) on bone mineral density (BMD) in postmenopausal Korean women with low BMD. METHODS: This retrospective cohort study included 74 postmenopausal women who received MHT for at least 1 year and had a BMD T-score of less than -2.0. Maintaining the same MHT regimen, these women were divided into two groups: oral placebo group (n = 44) and a pamidronate group of patients with gastrointestinal discomfort (n = 30) who received 15-30 mg pamidronate intravenously every 3-12 months. BMD was reviewed at 12-month follow-up. Bone resorption markers in both groups, urinary deoxypyridinoline levels in the placebo group, and serum N-telopeptide of type I collagen in the pamidronate group were assessed at 6 and 12 months. RESULTS: At baseline, the body mass index (BMI), duration of previous MHT, and femur neck (FN) BMD differed between the groups. Within-group analysis revealed that BMD of the lumbar spine (LS) and total hip (TH) significantly increased in the placebo group, whereas those of the LS, FN, and TH increased in the pamidronate group. The increase in BMD of LS was significantly greater in the pamidronate group, after adjusting for BMI and duration of previous MHT (mean change: 3.7% vs. 6.2%; P < 0.001). There were no changes in bone resorption markers in either group. CONCLUSIONS: Adding intravenous pamidronate to ongoing MHT for 12 months might increase LS BMD in postmenopausal Korean women with low BMD.

Assessment of patient-reported outcomes (PROs): treatment satisfaction, medication adherence, and quality of life (QoL) and the associated factors in postmenopausal osteoporosis (PMO) patients in Korea.

Patient-reported outcomes (PROs) provide practical guides for treatment; however, studies that have evaluated PROs of women in Korea with postmenopausal osteoporosis (PMO) are lacking. This cross-sectional, multi-center (29 nationwide hospitals) study, performed from March 2013 to July 2014, aimed to assess PROs related to treatment satisfaction, medication adherence, and quality of life (QoL) in Korean PMO women using osteoporosis medication for prevention/treatment. Patient demographics, clinical characteristics, treatment patterns, PROs, and experience using medication were collected. The 14-item Treatment Satisfaction Questionnaire for Medication (TSQM) (score-range, 0-100; domains: effectiveness, side effects, convenience, global satisfaction), Osteoporosis-Specific Morisky Medication Adherence Scale (OS-MMAS) (score-range, 0-8), and EuroQol-5 dimensions questionnaire (index score range, - 0.22 to 1.0; EuroQol visual analog scale score range, 0-100) were used. To investigate factors associated with PROs, linear (treatment satisfaction/QoL) or logistic (medication adherence) regression analyses were conducted. A total of 1804 patients (age, 62 years) were investigated; 60.1% used bisphosphonate, with the majority (67.2%) using weekly medication, 27.8% used daily hormone replacement therapy, and 12.1% used daily selective estrogen receptor modulator. Several patients reported gastrointestinal (GI) events (31.6%) and dental visits due to problems (24.1%) while using medication. Factors associated with the highest OS-MMAS domain scores were convenience and global satisfaction. GI events were associated with non-adherence. TSQM scores for effectiveness, side effects, and GI risk factors were significantly associated with QoL. Our study elaborately assessed the factors associated with PROs of Korean PMO women. Based on our findings, appropriate treatment-related adjustments such as frequency/choice of medications and GI risk management may improve PROs.

Menopausal hormone therapy and mild cognitive impairment: a randomized, placebo-controlled trial.

OBJECTIVE: The aim of the study was to explore the therapeutic potential of menopausal hormone therapy (MHT) in women with mild cognitive impairment (MCI). METHODS: Thirty-seven postmenopausal women (age range: 57-82 y) with multiple-domain, amnestic subtype MCI were randomly assigned to either placebo (n = 18) or MHT (n = 19) for 24 months (percutaneous estradiol [E2] gel [0.1%, 2 mg/d] and oral micronized progesterone [MP4] [100 mg/d]). All participants received donepezil, and apolipoprotein E genotype was determined. The primary endpoint was general cognitive function: Alzheimer's disease Assessment Scale, cognitive subscale, the Korean version of Mini-Mental State Examination (K-MMSE), and the Korean version of the Montreal Cognitive Assessment (MoCA_K) were performed in-person every 6 months. RESULTS: Twenty-one participants (placebo 13, MHT 8) completed the trial (56.8%). Progression rates to dementia were 52.9% (9/17) in the placebo group and 44.4% (8/18) in the MHT group. Within-group analysis showed that all three tests significantly worsened during the trial in the placebo, but not the MHT groups. Analysis adjusted for ε4 allele demonstrated that MHT significantly reduced deterioration of MoCA_K score, a sensitive tool for assessing global cognition in MCI (P = 0.0261). Compared with the control group, both MoCA_K (P = 0.043; mean difference, 3.85; 95% CI, -0.46 to 8.16) and K-MMSE (P = 0.0319; mean difference, 3.26; 95% CI, 0.04-6.48) scores were significantly better at 24 months in the MHT group. CONCLUSIONS: Long-term MHT using percutaneous E2 gel and oral MP4 might attenuate cognitive decline in postmenopausal women with MCI.

Effects of Combination Therapy of Alendronate and Hormonal Therapy on Bone Mineral Density in Postmenopausal Korean Women: Multicenter, Randomized Controlled Clinical Trial.

This study evaluated the effects of combination treatment with alendronate (ALEN) and hormone therapy (HT) on bone mineral density (BMD) in postmenopausal Korean women. This multicenter, randomized, controlled clinical trial enrolled 344 postmenopausal women with low BMD. The women received HT (0.625 mg/day of conjugated equine estrogen and 2.5 mg/day of medroxyprogesterone acetate) alone or in combination with ALEN (10 mg/day) for 1 year. Changes in BMD and biochemical markers of bone turnover were evaluated. Data from 203 women (HT alone, 99; combination treatment, 104) who completed this study were analyzed. BMD at the lumbar spine and total hip increased significantly in both treatment groups after 1 year. There were no significant differences between HT alone vs. the combination of ALEN and HT in mean BMD increase at the lumbar spine (6.9% vs. 7.9%) and total hip (3.7% vs. 3.8%). Combined therapy suppressed serum osteocalcin and urinary deoxypyridinoline to a greater extent than HT alone. In conclusion, compared to HT alone, combination treatment with ALEN and HT for 1 year did not offer a benefit in BMD in postmenopausal Korean women with low BMD.

Perceptions of Postmenopausal Symptoms and Treatment Options among Middle-Aged Korean Women.

PURPOSE: To investigate the perceptions of postmenopausal symptoms and treatment options among middle-aged Korean women. MATERIALS AND METHODS: This cross-sectional study included 2330 Korean women. The women were administered a structured questionnaire to collect sociodemographic data and information regarding menopause and its treatment. RESULTS: More than half (65%) of the participants perceived menopause as a disease, and 66.8% knew hormone therapy (HT) is available for menopausal symptom treatment. However, only 19.7% of participants visited clinics for HT. The most common reasons for having negative views about HT were its adverse reactions (47.3%) and concerns about developing cancer (41.1%). For symptom management, 36.5% of the participants tried lifestyle modification instead of HT. CONCLUSION: The majority of Korean women regarded menopause as a disease. They were aware of HT for menopausal symptom treatment, but the use of HT was relatively low. Education about the safety and positive effects of HT and the importance of professional healthcare should be provided.

Effects of long-term postoperative dienogest use for treatment of endometriosis on bone mineral density.

OBJECTIVE: This study was conducted to evaluate the effects of long-term postoperative dienogest (DNG) use for the treatment of endometriosis on bone mineral density (BMD). STUDY DESIGN: Sixty reproductive-aged women who underwent conservative surgery for endometriomas and received postoperative DNG (2mg/day) for at least 12 months to prevent recurrence were analyzed. BMD was measured before and after DNG treatment by using dual energy X-ray absorptiometry, and changes in BMD were evaluated. RESULTS: Mean patient age was 30.5 years, and mean duration of DNG treatment was 18.6 months. BMD at the lumbar spine significantly decreased after the first 6 months (-2.2%), and 1year (-2.7%) of DNG treatment, compared to baseline. The proportion of women who had significantly decreased BMD at the lumbar spine after 1year was 75% (45/60). In addition, BMD at the femur neck also decreased significantly after 1year (-2.8%). BMDs after 2 years were not different from those after 1year at both sites in 24 women who received DNG for ≥2years. In addition, there were no differences in baseline characteristics between women who had significantly reduced BMD at the lumbar spine after 1year (N=45) and women who did not (N=15). CONCLUSION: This study suggests that long-term postoperative DNG treatment might have an adverse effect on BMD in reproductive-aged women. Bone loss mostly occurs during the first 6 months of treatment with DNG. A clinical trial is warranted to establish the effects of long-term DNG treatment on bone mass.

The age-related recurrence of endometrioma after conservative surgery.

OBJECTIVE: As endometrioma frequently recurs after conservative surgery, long-term postoperative medical treatment for the prevention of recurrence is necessary. However, it has not been elucidated whether long-term postoperative medical treatment is crucial to all patients until menopause. Thereupon, this study was conducted to evaluate the age-related recurrence patterns after conservative surgery for endometrioma. STUDY DESIGN: A retrospective cohort study was performed on a total of 420 reproductive-aged women who underwent conservative surgery for endometrioma between January 2000 and December 2010. Ultrasonography was used during the follow-up period to detect endometrioma recurrence. Patients were classified into two groups according to the use of postoperative medications. The first group was observation only, while the second received gonadotropin releasing hormone agonists followed by cyclic oral contraceptives. The cumulative recurrence rate of endometrioma was compared according to the age at surgery (20-29 years, 30-39 years, 40-45 years) within each group. Subgroup analysis was performed according to the age between the two groups. RESULTS: The median follow-up duration after surgery was 29.0 months (range 6-159 months) for all patients. After adjusting for parity, size and bilaterality of cyst, and stage with American Society for Reproductive Medicine classification of endometriosis which was statistically different, within the group of no treatment, the cumulative recurrence rate in 40-45 years (10.2%) was significantly lower compared with those in 20-29 years (43.3%; hazard ratio (HR)=0.04; 95% confidence interval (CI)=0.01-0.52) and 30-39 years (22.5%; HR=0.19; 95% CI=0.04-0.92). However, there were no differences within the group of postoperative medical treatment. When we compared between the two groups, the cumulative recurrence rate was significantly different in 20-29 years (8.1 vs 43.3%; p<0.001) and 30-39 years (5.4 vs 22.5%; p=0.007), but there was no difference in 40-45 years (4.5 vs 10.2%; p=0.901). CONCLUSIONS: Our preliminary results demonstrate that the risk of endometrioma recurrence decreases with age. After the age of forty, the recurrence rate does not differ according to the use of postoperative medication. Based on our results, postoperative medical treatment may be individualized according to the patient's age at the time of surgery. Further studies are needed to identify patients who may benefit from postoperative medication.

The Efficacy of Postoperative Cyclic Oral Contraceptives after Gonadotropin-Releasing Hormone Agonist Therapy to Prevent Endometrioma Recurrence in Adolescents.

STUDY OBJECTIVE: Young age is a possible risk factor of endometriosis recurrence after surgery. However, the efficacy of postoperative medical treatment has not been well addressed in adolescents. The purpose of this study was to evaluate whether postoperative medical treatment is as effective in adolescents as it is in adults in the prevention of endometrioma recurrence. DESIGN: A retrospective cohort study. SETTING: Samsung Medical Center, Seoul, Korea. PARTICIPANTS: This study included 176 reproductive-aged women who underwent conservative laparoscopic surgery for pathology-confirmed endometrioma. Women were classified into 2 groups according to age: adolescents (20 years of age and younger, n = 34; group I) and reproductive-aged women (aged 25-35 years, n = 142; group II). INTERVENTIONS: The same surgeon performed all of the surgeries for uniformity. Postoperatively, patients were treated monthly with a gonadotropin-releasing hormone agonist depot for 3-6 months, followed by cyclic oral contraceptives. MAIN OUTCOME MEASURES: Endometrioma recurrence was determined using ultrasonography. The recurrence rate of endometrioma was compared between the 2 groups. RESULTS: During the treatment period (median, 41.0 months; range, 6-159 months), recurrence was noted in 8 cases (4.5%). After adjusting for confounders (which were statistically different between the groups), the cumulative proportion of recurrent endometriomas after 60 months was comparable between the 2 groups (5.3% in group I and 8.5% in group II). CONCLUSION: Long-term postoperative medical treatment with cyclic oral contraceptives after a gonadotropin-releasing hormone agonist can be as effective in adolescents as it is in adults in the prevention of endometrioma recurrence.

Recent trends in contraceptive use among Korean adolescents: Results from a nationwide survey from year 2013 to 2015.

OBJECTIVE: This study was aimed to evaluate the recent trends in contraceptive use among Korean adolescents. METHODS: Data reviewed were from the 2013-2015 Korean Youth Risk Behavior Web-based Survey, which is a stratified, multistage-sampling designed online-based research project performed annually by the Korean government to ensure a nationally representative sample of Korean adolescence. Eight questions related to the topic of contraception were reviewed for the outcome variables. RESULTS: A total of 212,538 adolescents attending middle school and high school participated in the survey, and 8,755 students among them who were sexually active were included in the study. The percentage of contraceptive use showed a steady increase from 39% in 2013 to 48.7% in 2015; however, the proportion of adolescents who have never used any kind of contraception still remains high. Highly effective methods such as oral contraceptives and intrauterine devices were used by only 10% to 15% of sexually active adolescents. CONCLUSION: The present study demonstrates the status of contraceptive use among Korean adolescents. Our data have the potential to help healthcare providers to formulate policies and develop interventions for encouraging effective contraceptive use among sexually active Korean adolescents.

Gonadotropin-releasing hormone agonist with add-back treatment is as effective and tolerable as dienogest in preventing pain recurrence after laparoscopic surgery for endometriosis.

PURPOSE: This study was performed to compare the efficacy and tolerability of GnRH agonist with add-back therapy versus dienogest treatment for preventing pelvic pain recurrence after laparoscopic surgery for endometriosis. METHODS: Sixty-four reproductive-aged women who underwent laparoscopic surgery for endometriosis received post-operative medical treatment with either GnRH agonist plus 17ß-estradiol and norethisterone acetate (n = 28) or dienogest (n = 36) for 6 months. The pre- to post-treatment changes in pain were assessed using a visual analogue scale, and changes in quality-of-life and menopausal symptoms were measured by questionnaire. RESULTS: Visual analogue scale pain score decreased significantly for both treatments with no significant differences between groups. Neither physical, psychological, social, and environmental components of quality-of-life nor menopausal rating scale score were significantly different between the two groups. Bone mineral density at the lumbar spine declined significantly in both treatment groups (-2.5 % for GnRH agonist plus add-back and -2.3 % for dienogest), with no significant difference between the two groups. CONCLUSION: GnRH agonist and add-back therapy using 17ß-estradiol and norethisterone acetate are as effective and tolerable as dienogest for the prevention of pelvic pain recurrence after laparoscopic surgery for endometriosis.