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Clinical Perspectives on Women’s Reproductive Health: Challenges and Management Strategies

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Obstetrics & Gynecology".

Deadline for manuscript submissions: 30 December 2025 | Viewed by 10902

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Prof. Dr. Seok Kyo Seo

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Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
Interests: endometriosis; ovarian endometrioma; fertilization; polycystic ovary syndrome; reproductive health; prepubertal and postpubertal; ovarian; cervical; postmenopausal women; hormone replacement therapy

Special Issue Information

Dear Colleagues,

In recent years, the prevalence of gynecological conditions such as endometriosis and polycystic ovary syndrome (PCOS) has shown a marked increase among women of reproductive age. These chronic disorders significantly impact reproductive function and long-term metabolic health. Recent advancements in clinical and translational research have led to the development of fertility-preserving strategies in endometriosis, including refined surgical techniques and tailored hormonal therapies. Similarly, evolving insights into the heterogeneity of PCOS have contributed to improved diagnostic algorithms and individualized treatment approaches.

In parallel, increasing attention is being given to reproductive aging and the health of postmenopausal women, particularly regarding the impact of estrogen deficiency on sarcopenia and overall metabolic resilience. Evidence supporting the role of hormone replacement therapy (HRT) in maintaining musculoskeletal health continues to grow, warranting further exploration through well-designed clinical studies.

This Special Issue aims to highlight current challenges and evolving perspectives in women’s reproductive health, with a focus on the increasing prevalence of endometriosis and PCOS, recent advances in therapeutic approaches, and the implications of hormonal changes in postmenopausal health, in light of the most up-to-date clinical evidence.

Prof. Dr. Seok Kyo Seo
Guest Editor

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Keywords

endometriosis
ovarian endometrioma
polycystic ovary syndrome
reproductive health
cervical
postmenopausal women
hormone replacement therapy
sarcopenia

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Published Papers (7 papers)

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Research

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13 pages, 1964 KB

Open AccessArticle

HMGB-1 Increases Proinflammatory Reaction via TLR4 in Human Granulosa Cells of Endometriosis

by Hye In Kim, Kyung Hee Kim, SiHyun Cho, Young Sik Choi, Byung Seok Lee, Seung Joo Chon and Bo Hyon Yun

J. Clin. Med. 2025, 14(21), 7532; https://doi.org/10.3390/jcm14217532 - 24 Oct 2025

Viewed by 280

Abstract

Background/Objectives: Oxidative stress is a critical factor in the development and progression of endometriosis. Granulosa cells, which reside near oocytes in follicles, exhibit steroidogenic activity, and, consequently, influence oocyte quality. Increased oxidative stress may induce the danger signal such as HMGB-1 in granulosa cells and eventually change the follicular environment of patients with endometriosis. This study aimed to demonstrate that HMGB-1 and its receptors, TLR4 and RAGE, play important roles in the changes in the follicular environment in infertile patients with endometriosis. Methods: In the immortalized human granulosa cell line (hGL5), cell proliferation and apoptosis assay, ELISA for estradiol, qRT-PCR for HMGB-1 and TLR4, Western blot for apoptosis-related and NF-κB pathway-related proteins, and ELISA for inflammatory molecules IL-1β and IL-6 were performed after H₂O₂ treatment. Results: H₂O₂ treatment to the hGL5 cell line decreased cell proliferation via apoptosis and, as a result, decreased steroidogenesis. Also, it increased the gene expression of HMGB-1 and TLR4, increased the protein expression related to the NF-κB pathway, and increased the release of inflammatory molecules IL-1β and IL-6. Conclusions: The results indicate that oxidative stress associated with endometriosis may increase inflammation by interacting with HMGB-1 and TLR4 and activating the NF-κB pathway to increase proinflammatory responses. The findings of this study may provide insight into endometriosis with decreased oocyte quality. Full article

(This article belongs to the Special Issue Clinical Perspectives on Women’s Reproductive Health: Challenges and Management Strategies)

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13 pages, 1374 KB

Open AccessArticle

Tissue-Specific Genomic Evolution Despite Shared MED12 Mutations in Benign Tumors

by Jeong Namkung, Sang Ho Park, Ayoung Hwang, Hae Seo, Jooyoung Park, Moonyoung Lee, Hyunkyung Kim, Jungmin Choi and Jae Yen Song

J. Clin. Med. 2025, 14(20), 7325; https://doi.org/10.3390/jcm14207325 - 16 Oct 2025

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Abstract

Background/Objectives: Uterine leiomyomas (ULs) and breast fibroadenomas (FAs) are the most common benign tumors in women, both arising in hormone-responsive mesenchymal tissues and often co-occurring during reproductive years. Despite their shared hormonal sensitivity and frequent MED12 mutations, their downstream molecular evolution remains poorly characterized. This study aimed to investigate whether ULs and FAs, though initiated by similar genetic alterations, diverge in their oncogenic trajectories, thereby addressing the molecular basis for their distinct clinical behaviors. Methods: We performed whole-exome sequencing (WES) on 15 uterine leiomyomas and 7 publicly available fibroadenomas with matched normal controls to compare somatic mutations, copy number alterations (CNAs), and mutational signatures. All UL samples were derived from Korean patients who underwent surgical treatment at a tertiary hospital between 2017 and 2019. Somatic variants were analyzed using MuTect2 and Strelka2. FACETS was used to estimate copy number changes in individual samples, and GISTIC2 to identify recurrent and statistically significant copy number alterations across patient cohorts. Mutational processes were inferred using SigProfiler. Microsatellite instability status was determined with MSIsensor2. The study was approved by the Institutional Review Board (UC17SNSI0092). Results: Comparative whole-exome sequencing of 15 ULs and 7 FAs from matched tumor-normal samples in an East Asian cohort confirmed both tumor types harbor identical MED12 p.G44D mutations, establishing shared molecular initiation. However, post-initiation evolution diverged dramatically: ULs exhibited chromosomal instability with 15 copy number amplifications, 6 of which affected oncogenes, but relatively modest point mutations. In contrast, FAs remained chromosomally stable but hypermutated, harboring 1.47× more variants than ULs despite lower tumor purity. Notably, one histologically benign FA harbored multiple loss-of-function mutations plus an EGFR gain-of-function mutation typically associated with malignant breast cancer, challenging traditional benign-malignant classifications. Conclusions: Despite sharing a common initiating mutation in MED12, ULs and FAs evolve through fundamentally distinct genomic pathways. UL evolves through chromosomal instability, whereas FA evolves through a mutator phenotype, with important implications for understanding tumor biology and molecular-based risk stratification. These findings support a paradigm of tissue-specific oncogenic evolution and underscore the potential clinical utility of genomic profiling in distinguishing benign tumors with atypical molecular features. Full article

(This article belongs to the Special Issue Clinical Perspectives on Women’s Reproductive Health: Challenges and Management Strategies)

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11 pages, 327 KB

Open AccessArticle

Metabolic Mediation of the Association Between Hyperandrogenism and Paratubal Cysts in Polycystic Ovary Syndrome: A Structural Equation Modeling Approach

by Jin Kyung Baek, Chae Eun Hong, Hee Yon Kim and Bo Hyon Yun

J. Clin. Med. 2025, 14(15), 5545; https://doi.org/10.3390/jcm14155545 - 6 Aug 2025

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Abstract

Objectives: Paratubal cysts (PTCs) are embryological remnants and are potentially hormonally responsive. Since hyperandrogenism (HA) is representative of polycystic ovary syndrome (PCOS), we examined whether biochemical hyperandrogenism is associated with PTCs in women with PCOS and if body mass index (BMI) and insulin resistance (IR) mediate this association. Methods: This retrospective study included 577 women diagnosed with PCOS at a tertiary academic center from 2010 to 2018. Clinical data included age at diagnosis, BMI, and diagnoses of hypertension, non-alcoholic fatty liver disease, and metabolic syndrome. Laboratory measures included total testosterone, sex hormone-binding globulin, anti-Müllerian hormone, luteinizing hormone, fasting glucose, insulin, and triglycerides (TG). Derived indices included a free androgen index (FAI), homeostasis model assessment of insulin resistance (HOMA-IR), and fasting glucose-to-insulin ratio. PTCs were identified through imaging or surgical findings. Structural equation modeling (SEM) assessed direct and indirect relationships between FAI, BMI, HOMA-IR, and PTCs, while adjusting for diagnostic age. Results: PTCs were identified in 2.77% of participants. BMI, FAI, TG, and IR indices were significantly higher for women with PTCs than those without PTCs. SEM revealed significant indirect effects of FAI on PTCs via BMI and HOMA-IR. The direct effect was negative, resulting in a non-significant total effect. A sensitivity model using HOMA-IR as the predictor showed a significant direct effect on PTCs without mediation via FAI. Conclusions: Biochemical HA may influence PTC development in PCOS through metabolic pathways, establishing the need to consider metabolic context when evaluating adnexal cysts in hyperandrogenic women. Full article

(This article belongs to the Special Issue Clinical Perspectives on Women’s Reproductive Health: Challenges and Management Strategies)

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14 pages, 5817 KB

Open AccessArticle

Recent Changes in Sexually Transmitted Infection in Korea: A Population-Based Analysis

by Jae Yen Song, Kang Seob Kim, Chang Hee Han and Sangrak Bae

J. Clin. Med. 2025, 14(14), 5145; https://doi.org/10.3390/jcm14145145 - 20 Jul 2025

Cited by 2 | Viewed by 3351

Abstract

Background: The objective of this study is to investigate the prevalence and epidemiological changes of major sexually transmitted infections (STIs) in Korea over the past decade. Methods: From 2010 to 2021, patients diagnosed with STIs based on ICD-10 codes were analyzed using Korean Health insurance data. The analysis included the number of patients, prevalence, and age-specific prevalence (in 5-year intervals) over this period. We examined changes in disease patterns over time by analyzing the annual trends and age-specific prevalence of bacterial STIs such as chlamydia, mycoplasma, gonorrhea, and syphilis; viral STIs such as genital herpes, human papillomavirus (HPV), and human immunodeficiency virus (HIV); and other infections including scabies, pubic lice, and trichomoniasis. Results: In 2010, the STI with the highest prevalence due to an infectious pathogen was trichomoniasis (256.65/100,000), while latent syphilis had the lowest prevalence (5.29/100,000). In 2021, the STI with the highest prevalence was genital herpes (254.54 per 100,000 persons), and latent syphilis continued to have the lowest prevalence. Bacterial STIs showed a decreasing trend. Viral STIs showed a continuous increase throughout the study period, with anogenital warts (AGW) having the highest rate of increase. Other infections showed a decreasing trend. HIV and AGW in men showed a rapid increase. Gender differences varied depending on the disease. Conclusions: While bacterial STIs have gradually declined, viral STIs have continued to increase during last decade. The characteristics of each pathogen vary according to age and gender, necessitating the establishment of risk groups for each pathogen and the development of prevention policies accordingly. Full article

(This article belongs to the Special Issue Clinical Perspectives on Women’s Reproductive Health: Challenges and Management Strategies)

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12 pages, 733 KB

Open AccessArticle

Effects of Endometriosis on Anti-Müllerian Hormone

by Yun Soo Chung, Euna Choi, Jin Kyung Baek, Heeyon Kim and Bo Hyon Yun

J. Clin. Med. 2025, 14(13), 4495; https://doi.org/10.3390/jcm14134495 - 25 Jun 2025

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Abstract

Background/Objectives: As the population of women with endometriosis increases, approximately 10% of those of reproductive age experience symptoms such as pelvic pain, painful menstruation, and infertility. Individuals with endometriosis usually undergo multiple surgeries due to the high recurrence rate of the condition. However, ovarian surgery tends to reduce the ovarian reserve, presenting a dilemma when deciding whether to recommend surgery or medical treatment for women of reproductive age. The impact of endometriomas on the residual volume of ovarian tissue remains controversial, and it is unclear whether endometriosis itself or endometriomas are the primary problem. In this study, we aimed to investigate whether women with endometriosis have lower levels of anti-Müllerian hormone than women with healthy ovaries before treatment initiation. Methods: A total of 298 participants enrolled in the endometriosis cohort at Severance Hospital, Korea, from 1 October 2020 to 1 July 2024 were included in this study. Of these, 63 participants were from a retrospective study, and 235 were from a prospective study. Due to the use of different assay methods between the reference values and anti-Müllerian hormone measurements from Severance Hospital, a correction was applied using the regression equation. The mean anti-Müllerian hormone levels for individuals with endometriosis were corrected with the regression equation and compared to those of the reference group for each age group using a one-sample t-test. Results: Anti-Müllerian hormone levels decreased with age in the endometriosis group. When comparing mean anti-Müllerian hormone concentrations between the endometriosis group and reference values, among 168 participants aged 20–31 years, the corrected mean anti-Müllerian hormone concentration was 5.96 ± 3.22 ng/mL, higher than the reference value of 4.94 ± 0.17 ng/mL (p < 0.01). Among 31 participants aged 35–37 years, the corrected average anti-Müllerian hormone value was 4.33 ± 3.06 ng/mL, compared to the reference anti-Müllerian hormone level of 3.22 ± 0.15 ng/mL (p = 0.05). There were no significant differences in corrected anti-Müllerian hormone levels between the 32–34-, 38–40-, 41–43-, and ≥44 years age groups. Conclusions: Patients with endometriosis, especially those aged 20–31 years, tended to have higher anti-Müllerian hormone levels than did individuals with healthy ovaries. In other age groups, there were no differences. Given that these levels do not differ significantly across age groups, it is difficult to conclude that patients with endometriosis have a reduced ovarian reserve. Full article

(This article belongs to the Special Issue Clinical Perspectives on Women’s Reproductive Health: Challenges and Management Strategies)

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12 pages, 4200 KB

Open AccessArticle

The Development of an Ultrasound-Based Scoring System for the Prediction of Interstitial Pregnancy

by Yun Ji Jung, Hyun-Soo Zhang, Eun Jin Lee, Hayan Kwon, Ja-Young Kwon, Young-Han Kim and JoonHo Lee

J. Clin. Med. 2025, 14(12), 4238; https://doi.org/10.3390/jcm14124238 - 14 Jun 2025

Viewed by 936

Abstract

Background/Objectives: Diagnosing interstitial pregnancy (IP) using ultrasonography can be challenging, as it is often mistaken for eccentrically located intrauterine pregnancy (IUP). In this retrospective cohort study, we aimed to develop a predictive scoring model using multiple clinical factors to enhance the diagnosis of IP and facilitate timely interventions in suspected cases. Methods: We enrolled 63 pregnant women with a diagnosis of suspected IP who visited a single tertiary center between January 2006 and December 2023. Data on the clinical risk factors, symptoms, laboratory test results, and ultrasound findings were analyzed. A statistical predictive score was developed using logistic regression analysis with feature selection based on the least absolute shrinkage and selection operator to optimize the predictive accuracy and clinical applicability. Results: From a total of 12 factors, a scoring model was constructed from the three most prominent factors—ultrasound findings showing no surrounding endometrium, myometrial thinning of less than 5 mm, and vaginal bleeding—all of which demonstrated high feature importance. This predictive score identified IP with a negative predictive value of 0.950 in the low-risk group and a positive predictive value of 1.000 in the high-risk group, whereas the overall area under the curve was 0.998 (95% confidence interval, 0.992–1.000). Conclusions: The statistically derived predictive model––ultrasound showing no surrounding endometrium and myometrial thinning < 5 mm combined with vaginal bleeding––demonstrated high accuracy and practical applicability for IP diagnosis, providing a robust tool to enhance clinical decision-making and optimize routine management strategies for IP. Full article

(This article belongs to the Special Issue Clinical Perspectives on Women’s Reproductive Health: Challenges and Management Strategies)

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Review

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17 pages, 556 KB

Open AccessReview

Obesity as a Part of Polycysric Ovary Syndrome (PCOS)—A Review of Pathophysiology and Comprehensive Therapeutic Strategies

by Jovan Bila, Jelena Dotlic, Mladen Andjic, Katarina Ivanovic, Jelena Micic, Lidija Tulic, Miljan Pupovac, Jelena Stojnic, Ivana Vukovic and Stefan Ivanovic

J. Clin. Med. 2025, 14(16), 5642; https://doi.org/10.3390/jcm14165642 - 9 Aug 2025

Viewed by 3349

Abstract

Background/Objectives: Polycystic Ovary Syndrome (PCOS), as a multifactorial chronic disease, can cause heterogeneous metabolic, physical, and psychological disorders as well as infertility in both obese and non-obese patients. Therefore, this review aimed to present differences in pathophysiology, clinical presentation, and therapy in obese and non-obese patients with PCOS. Methods: A non-systematic review was conducted by searching papers published in English from 2010 to 2024 in MEDLINE. Results: Obesity in PCOS significantly contributes to IR and worsens metabolic dysfunction. Lifestyle modifications, including a balanced diet and regular exercise, are the first line of treatment. Pharmacological therapies, such as metformin, GLP-1 receptor agonists, myoinositol, and resveratrol, are used to improve insulin sensitivity, regulate the hormonal milieu, and reduce hyperandrogenism. Metformin is widely used to improve glucose metabolism and reduce androgen levels, while myoinositol is effective in promoting ovarian function. GLP-1 receptor agonists and resveratrol improve metabolic and reproductive outcomes. For patients with severe obesity, bariatric surgery offers substantial improvements in body composition, metabolic function, and fertility. Combination therapies, such as metformin and GLP-1 receptor agonists, provide comprehensive treatment for both reproductive and metabolic aspects of PCOS. Conclusions: The first-line treatment for PCOS is a lifestyle-modifying strategy. PCOS patients with insulin resistance and obesity would mostly benefit from combination therapy with metformin and GLP-1 receptor agonists. Full article

(This article belongs to the Special Issue Clinical Perspectives on Women’s Reproductive Health: Challenges and Management Strategies)

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