Clinical Characteristics of Gynecologic Problems During Childhood in the Korean Population

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.

Efficacy of Post-Operative Medication to Prevent Recurrence of Endometrioma: Cyclic Oral Contraceptive (OC) After Gonadotropin-Releasing Hormone (GnRH) Agonist Versus Dienogest

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.

Menopausal Hormone Therapy and Progression of Non-Alcoholic Fatty Liver Disease in Postmenopausal Women: A 12-Month Study

Objective@#This study was conducted to evaluate the effects of menopausal hormone therapy (MHT) on the progression of non-alcoholic fatty liver disease (NAFLD) in postmenopausal women. @*Materials and Methods@#We included 515 women who received MHT for 12 months. Changes in NAFLD was evaluated by ultrasonography (progressiono progression) were compared before and after 12 months of MHT based on the route of estrogen administration (transdermal/oral). In addition, changes in NAFLD according to estrogen dose and type of progestogen were evaluated. @*Results@#Baseline characteristics did not differ between patients who received transdermal (n=82) vs. oral (n=433) MHT. After 12 months of transdermal MHT, the prevalence of NAFLD decreased from 23.2% to 18.3% and the progression of NAFLD was observed in 3.7% patients, but this was not significantly different from those taking oral MHT. NAFLD progression was more common in women who had NAFLD at baseline and who received on oral MHT regimen compared to transdermal regimen (12.4% vs. 5.3%), however, differences were not statistically significant. In the oral MHT group, progression of NAFLD was significantly more common in standard-dose than low-dose (P=0.039). There was no significant difference in NAFLD progression according to the type of progestogen in patients using standard dose of estrogen. @*Conclusion@#Our findings suggest that the route of estrogen administration and oral dose of estrogen might affect progression of NAFLD in women with NAFLD at baseline.

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.

Effects of different add-back regimens on hypoestrogenic problems by postoperative gonadotropin-releasing hormone agonist treatment in endometriosis

OBJECTIVE: To compare the efficacy of different add-back regimens on hypoestrogenic symptoms during postoperative gonadotropin-releasing hormone (GnRH) agonist treatment in endometriosis patients. METHODS: This prospective cohort study included reproductive-aged women who underwent conservative laparoscopic surgery for ovarian endometriosis and received add-back therapy during a 6-month course of GnRH agonist therapy after surgery. Participants received one of four different add-back regimens: 1 mg of estradiol valerate, 2.5 mg of tibolone, or a combination of 1 mg of estradiol and 2 mg of drospirenone or 0.5 mg of norethisterone acetate. Changes in quality of life, hypoestrogenic symptoms, and bone mineral density were compared according to add-back regimens. RESULTS: A total of 57 participants completed a 6-month course of GnRH agonist and add-back therapy. All components of quality of life did not differ across groups. However, within the same treatment group, social relationship factors decreased significantly with estradiol valerate and tibolone alone, and environmental factors decreased significantly with estradiol valerate alone. Menopausal Rating Scale score did not change significantly, but the incidence of hot flushes significantly decreased with a combination of estradiol and norethisterone acetate. Bone mineral densities at the lumbar spine declined significantly after treatment in all groups except with a combination of estradiol and norethisterone acetate. CONCLUSION: This preliminary study suggests that an add-back regimen containing estradiol valerate and norethisterone acetate may have better efficacy in terms of quality of life, hypoestrogenism-associated symptoms, and bone mineral density.

Estrogen-mediated Height Control in Girls with Marfan Syndrome

This study evaluated the efficacy of a stepwise regimen of estradiol valerate for height control in girls with Marfan syndrome. Eight girls with Marfan syndrome who had completed estrogen treatment for height control were included. Estradiol valerate was started at a dose of 2 mg/day, and then was increased. The projected final height was estimated using the initial height percentile (on a disease-specific growth curve for Korean Marfan syndrome [gcPFHt]), and the initial bone age (baPFHt). After the estrogen treatment, the projected final height was compared to the actual final height (FHt). The median baseline chronological and bone age were 10.0 and 10.5 years, respectively. After a median of 36.5 months of treatment, the median FHt (172.6 cm) was shorter than the median gcPFHt (181.0 cm) and baPFHt (175.9 cm). In the six patients who started treatment before the age of 11 years, the median FHt (171.8 cm) was shorter than the median gcPFHt (181.5 cm) and baPFHt (177.4 cm) after treatment. The median differences between the FHt and gcPFHt and baPFHt were 9.2 and 8.3 cm, respectively. In two patients started treatment after the age of 11, the differences between FHt and gcPFHt, and baPFHt after treatment were -4 and 1.4 cm, and -1.2 and 0 cm for each case, respectively. A stepwise increasing regimen of estradiol valerate may be an effective treatment for height control in girls with Marfan syndrome, especially when started under 11 years old.

A FRAX Experience in Korea: Fracture Risk Probabilities with a Country-specific Versus a Surrogate Model

BACKGROUND: Recently, a Korean fracture-risk assessment tool (FRAX) model has become available, but large prospective cohort studies, which are needed to validate the model, are still lacking, and there has been little effort to evaluate its usefulness. This study evaluated the clinical usefulness of the FRAX model, a FRAX developed by the World Health Organization, in Korea. METHODS: In 405 postmenopausal women and 139 men with a proximal femoral fracture, 10-year predicted fracture probabilities calculated by the Korean FRAX model (a country-specific model) were compared with the probabilities calculated with a FRAX model for Japan, which has a similar ethnic background (surrogate model). RESULTS: The 10-year probabilities of major osteoporotic and hip fractures calculated by the Korean model were significantly lower than those calculated by the Japanese model in women and men. The fracture probabilities calculated by each model increased significantly with age in both sexes. In patients aged 70 or older, however, there was a significant difference between the two models. In addition, the Korean model led to lower probabilities for major osteoporotic fracture and hip fracture in women when BMD was excluded from the model than when it was included. CONCLUSIONS: The 10-year fracture probabilities calculated with FRAX models might differ between country-specific and surrogate models, and caution is needed when applying a surrogate model to a new population. A large prospective study is warranted to validate the country-specific Korean model in the general population.

Effect of Transdermal Estrogen Therapy on Bone Mineral Density in Postmenopausal Korean Women

OBJECTIVES: To evaluate the effects of transdermal estrogen therapy on bone mineral density (BMD) in postmenopausal Korean women. METHODS: A total of 149 healthy postmenopausal women were retrospectively evaluated: 100 were on hormone therapy (HT) and 49 were the control group. For the HT group, 54 applied estrogen transdermally using either a patch (n = 21) or gel (n = 33), and 46 took estrogen orally (conjugated estrogen 0.625 mg or equivalent). Demographic profiles and changes in BMD over two years were compared according to the route of the estrogen. RESULTS: No differences were found in age, age at menopause, parity, body mass index, and type of menopause among the oral, transdermal and control groups. Compared with controls, HT significantly increased BMD after 2 years in both the lumbar spine and the total hip. The increases in BMD at both lumbar spine and hip were comparable between the oral and transdermal groups. There were also no differences in BMD changes according to progestogen addition in either the oral or transdermal groups. CONCLUSION: Transdermal estrogen therapy increases BMD, comparable to oral estrogen, in postmenopausal Korean women.

Clinical use of oral contraceptives

Since oral contraceptives (OCs) were first introduced in 1960, they have been used as a highly effective contraceptive method for over 50 years. Besides the prevention of pregnancy, they provide various non-contraceptive benefits. Well-known non-contraceptive benefits related to menstruation include reduction of dysmenorrhea and heavy menstrual bleeding. In addition, many women see improvements in acne and symptoms from premenstrual syndrome/premenstrual dysphoric disorder with OC use. In addition, OCs also can be used for the management of endometriosis or polycystic ovarian syndrome, and have also been reported to decrease the risk of ovarian and endometrial cancer. Consequently, many women may choose to use OCs in light of their non-contraceptive benefits. These non-contraceptive benefits can encourage women to select OCs as an useful option for contraception, improving their quality of life, and even providing public health benefits. Therefore, clinicians should be familiar with OCs and able to provide detailed information regarding their non-contraceptive benefits. The purpose of this article is to review the current evidence for the non-contraceptive benefits of OCs.

Impact of Lysophosphatidylcholine on the Plasminogen Activator System in Cultured Vascular Smooth Muscle Cells

The balance between tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) regulates fibrinolysis. PAI-1 expression increases in atherosclerotic arteries and vascular smooth muscle cells (VSMCs) are one of major constituents of atheroma. We investigated the impact of lysophosphatidylcholine (lysoPC), an active component of oxidized low-density lipoprotein, on the plasminogen activator system of the rat VSMCs. The lysoPC stimulated the protein and gene expressions of PAI-1 but did not affect the protein expression of t-PA. Fibrin overlay zymography revealed that lysoPC increased the activity of PAI-1 in the conditioned media, while concurrently decreasing that of free t-PA. Vitamin E inhibited the lysoPC-induced PAI-1 expression. Further, lysoPC increased the intracellular reactive oxygen species (ROS) formation. Caffeic acid phenethyl ester, an inhibitor of NF-kappaB, blocked this lysoPC effect. Indeed, lysoPC induced the NF-kappaB-mediated transcriptional activity as measured by luciferase reporter assay. In addition, genistein, an inhibitor of protein-tyrosine kinase (PTK), diminished the lysoPC effect, while 7,12-dimethylbenz[a]anthracene, a stimulator of PTK, stimulated PAI-1 production. In conclusion, lysoPC does not affect t-PA expression but induces PAI-1 expression in the VSMC by mediating NF-kappaB and the genistein-sensitive PTK signaling pathways via oxidative stress. Importantly, lysoPC stimulates the enzyme activity of PAI-1 and suppresses that of t-PA.

Impact of Oral Levonorgestrel for 1 Year on Mammographic Density in Menopausal Hormone Therapy / 대한폐경학회지

OBJECTIVES: We evaluated changes in mammographic density (MMGD) after hormone therapy (HT) using levonorgestrel (LNG) in Korean postmenopausal women. METHODS: In this retrospective study, 58 healthy postmenopausal women with no history of prior HT were included. Twenty-three women were given a cyclic regimen of estradiol valerate (E) 2 mg/day + LNG 0.075 mg/day and 25 untreated women served as a negative control and 10 women treated with continuous combined regimen of conjugated equine estrogen (CEE) 0.625 mg/day + medroxyprogesterone acetate (MPA) 2.5 mg/day as a positive control. Mammography was obtained at baseline and 1 year later, and MMGD was assessed. In addition, the change in the proportion of the dense area after HT was assessed using the J-image program. Data were analyzed with analysis of variance and chi-square or Fisher's exact test. RESULTS: There were no significant differences in baseline characteristics among three groups. After 1 year of HT, increase of BI-RADS grade in CEE + MPA group (7/9, 77.8%) was higher than in E + LNG group (2/16, 12.5%; P = 0.001). But there was no difference between untreated group (1/19, 5.3%) and E + LNG group (2/16, 12.5%; P = 0.446). In subgroup analysis of women with BI-RADS grade 3 at baseline, no significant difference. Changes in the proportion of dense areas assessed by the J-image program showed similar results. Regression analysis revealed that there was no correlation between baseline dense area and changes after HT in E + LNG group. CONCLUSION: HT using LNG did not influence MMGD in Korean postmenopausal women. Further study on breast cancer risk may be needed.

Impact of Oral Levonorgestrel for 1 Year on Mammographic Density in Menopausal Hormone Therapy / 대한폐경학회지

OBJECTIVES: We evaluated changes in mammographic density (MMGD) after hormone therapy (HT) using levonorgestrel (LNG) in Korean postmenopausal women. METHODS: In this retrospective study, 58 healthy postmenopausal women with no history of prior HT were included. Twenty-three women were given a cyclic regimen of estradiol valerate (E) 2 mg/day + LNG 0.075 mg/day and 25 untreated women served as a negative control and 10 women treated with continuous combined regimen of conjugated equine estrogen (CEE) 0.625 mg/day + medroxyprogesterone acetate (MPA) 2.5 mg/day as a positive control. Mammography was obtained at baseline and 1 year later, and MMGD was assessed. In addition, the change in the proportion of the dense area after HT was assessed using the J-image program. Data were analyzed with analysis of variance and chi-square or Fisher's exact test. RESULTS: There were no significant differences in baseline characteristics among three groups. After 1 year of HT, increase of BI-RADS grade in CEE + MPA group (7/9, 77.8%) was higher than in E + LNG group (2/16, 12.5%; P = 0.001). But there was no difference between untreated group (1/19, 5.3%) and E + LNG group (2/16, 12.5%; P = 0.446). In subgroup analysis of women with BI-RADS grade 3 at baseline, no significant difference. Changes in the proportion of dense areas assessed by the J-image program showed similar results. Regression analysis revealed that there was no correlation between baseline dense area and changes after HT in E + LNG group. CONCLUSION: HT using LNG did not influence MMGD in Korean postmenopausal women. Further study on breast cancer risk may be needed.

Determination of an Applicable FRAX Model in Korean Women

We investigated which of the three FRAX fracture risk assessment tool models is most applicable to Korean women. For 306 postmenopausal women (mean age, 77 yr) with a hip fracture, fracture probabilities were calculated using FRAX models from Japan, Turkey and China. Data on bone mineral density (BMD) at the femoral neck were available for 103 patients. Significant differences existed among the models, independent of the inclusion of BMD in the calculation of fracture probabilities. The probabilities of both major osteoporotic fractures and hip fractures were significantly higher in the Japanese model than in the Turkish or Chinese models. In all of the models, the probabilities of a major osteoporotic fracture, but not of a hip fracture, decreased significantly if calculated without BMD values. By applying the Japanese model, the ten-year probabilities for major osteoporotic and hip fractures increased significantly with age. Our results suggest that the Japanese FRAX model might be the most appropriate for Korean women.

GnRH Agonist Therapy to Protect Ovarian Function in Young Korean Breast Cancer Patients

The increased survival of patients with breast cancer has given rise to other problems associated with the complications of chemotherapy. One major complication is premature ovarian failure, an especially harmful outcome for women of reproductive age. This study was performed to evaluate the efficacy of GnRH agonist (GnRHa) treatment on protecting ovarian function in young breast cancer patients (30.59+/-5.1 yr) receiving chemotherapy after surgery. Twenty-two women were enrolled and given subcutaneous injections of leuprolide acetate (3.75 mg) every 4 weeks during chemotherapy. Follow-up laboratory tests (luteinizing hormone [LH], follicle stimulating hormone [FSH], and estradiol) were performed 1, 3, and 6 months after chemotherapy. Menstruation patterns and clinical symptoms were followed up for a mean duration of 35.6+/-1.7 months. FSH and LH levels were normal in all patients 6 months after completing chemotherapy (8.0+/-5.3, 4.4+/-2.7 mIU/mL, respectively). During follow-up, none of the patients complained of menopausal symptoms and 81.8% experienced recovery of menstruation. This report is the first trial of GnRHa as a treatment modality to protect ovarian function during adjuvant chemotherapy in young Korean breast cancer patients.

Clinical Analysis of Ovarian Insufficiency and Effects of Hormone Replacement Therapy in Korean Women with Alzheimer's Disease

BACKGROUND: Estrogen deficiency is linked to cardiovascular disease (CVD) and osteoporosis in women. Ovarian hormones are also presumed to play a key role in Alzheimer's disease (AD). This study was designed to investigate the clinical evidences of estrogen deficiency and therapeutic efficacy of hormone replacement (HRT) in women with AD. METHODS: Clinical tests indicative of ovarian insufficiency were performed in 44 female patients with AD (age: 49-81: 68.0+1.2, Mean+SEM). Out of 40 patients treated with HRT, 16 completed one-year follow-ups. Modification of risk factors for CVD and changes in bone mineral density with HRT were assessed. Periodic MMSE was performed to evaluate changes in cognitive function under HRT. RESULTS: All the patients except two were postmenopausal, and years since menopause were 18.2+1.8. Six patients had early menopause. Hypertension was detected in 9 patients, and one had history of CVD. Prevalence of osteoporosis at lumbar vertebrae or femur neck and that of fragility fracture were 57% and 39%, respectively. Sixteen patiens who completed one-year HRT were analyzed separately: HRT reduced significantly blood levels of total cholesterol, Lp(a), and glucose and increased HDL-cholesterol. HRT also prevented bone loss at both lumbar spine and femur neck. MMSE scores at 3, 6, and 12 months of HRT revealed no significant decline compared with baseline score. CONCLUSIONS: Female AD is late problem after menopause, and frequently associated with osteoporosis. In addition to beneficial modification of risk factors for CVD and prevention of further bone loss, HRT might inhibit cognitive decline assessed by MMSE in AD.