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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: closed (20 February 2026) | Viewed by 32153

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Prof. Dr. Błażej Męczekalski

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Department of Gynaecological Endocrinology, Poznan University of Medical Sciences, 60-535 Poznan, Poland
Interests: hypothalamic amenorrhea; menopause; polycystic ovary syndrome; premature ovarian insufficiency; hyperprolactinemia
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Dear Colleagues,

Gynecological endocrinology is a specific field of modern medicine that focuses on the field of physiological and pathological endocrine mechanisms related to the hypothalamic–pituitary–ovarian axis and also influences other endocrine glands (such as adrenal glands, thyroid glands, fat tissue and others), which have an impact on women’s health and hormonal disorders.

Over the last 2–3 decades, we observed interesting developments in gynaecological endocrinology both in the sense of research and the clinical field. At present, gynecological endocrinology must face new challenges arising in the context of etiopathogenesis, diagnosis, differential diagnosis and novel drugs.

This Special Issue aims to discuss the recent developments in the pathophysiology, diagnosis and treatment of different disorders in the field of gynecological endocrinology.

The topics of interest for this Special Issue include menstrual disorders, hyperandrogenization, puberty and related disorders, fertility and infertility and hormonal disorders during pregnancy, premenopause and menopause.

This Special Issue will also cover various hot research topics such as new contraception methods, endometriosis pathophysiology and treatment, functional hypothalamic amenorrhea treatment, premature ovarian insufficiency ethology and management and new advances in menopausal symptom treatments.

Prof. Dr. Błażej Męczekalski
Guest Editor

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Keywords

amenorrhea
puberty
PCOS
premature ovarian insufficiency
endometriosis
infertility
pregnancy
hormones
menopause

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Related Special Issue

Recent Developments in Gynecological Endocrinology: 2nd Edition in Journal of Clinical Medicine

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Research

Jump to: Review

14 pages, 1426 KB

Open AccessArticle

Endometriosis-Related Impairment in Assisted Reproductive Technologies: Inflammatory Profiles, Oocyte Competence, and Embryo Development

by Francesca Papini, Susanna Cappellini, Ilaria Marcacci, Ilaria Marzi, Elena Casarosa, Simona Daniele, Sara Macaluso, Amerigo Ferrari, Andrea Panattoni, Paolo Giovanni Artini and Vito Cela

J. Clin. Med. 2026, 15(5), 1723; https://doi.org/10.3390/jcm15051723 - 25 Feb 2026

Viewed by 536

Abstract

Background: Endometriosis is associated with infertility and impaired assisted reproductive technology (ART) outcomes, potentially due to an altered follicular microenvironment characterized by chronic inflammation. This study investigates the systemic and local inflammatory profiles in women with endometriosis and assesses their impact on oocyte and embryo quality using both static and dynamic embryo evaluation. Methods: A prospective, monocentric observational study enrolled 47 women undergoing controlled ovarian stimulation for ART, including 29 with laparoscopically confirmed endometriosis and 18 controls with tubal or male-factor infertility. Serum and follicular fluid cytokines (TGF-β1, NF-κB, IL-10, HIF-1α) were quantified. A sub-study analyzed embryo quality and development in 36 patients subdivided into static morphological assessment and dynamic time-lapse monitoring cohorts. Results: Endometriosis patients exhibited significantly elevated pro-inflammatory cytokines (TGF-β1, NF-κB) and reduced anti-inflammatory IL-10 in serum, alongside decreased NF-κB in follicular fluid. These alterations correlated with diminished ovarian reserve, reduced oocyte yield, and lower fertilization rates. Embryos from endometriosis patients showed increased multinucleation and persistent fragmentation, features more sensitively detected via dynamic time-lapse imaging. Clinical pregnancy rates were significantly lower in the endometriosis group. Conclusions: Endometriosis induces a dysregulated inflammatory follicular milieu that adversely affects oocyte competence and embryo morphodynamics. Dynamic embryo assessment provides enhanced detection of subtle developmental abnormalities. Integration of immunomodulatory strategies and advanced embryo monitoring may improve ART success in this population. Full article

(This article belongs to the Special Issue Recent Developments in Gynecological Endocrinology)

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16 pages, 923 KB

Open AccessArticle

Metabolic and Endocrine Alterations in Underweight and Normal-Weight Women with Functional Hypothalamic Amenorrhea

by Karolina Kowalczyk, Iga Szymańska, Olga Zawistowska, Julia Bieńkowska, Agnieszka Drosdzol-Cop and Paweł Madej

J. Clin. Med. 2025, 14(19), 7082; https://doi.org/10.3390/jcm14197082 - 7 Oct 2025

Cited by 1 | Viewed by 2991

Abstract

Background: Functional hypothalamic amenorrhea (FHA) is a form of chronic anovulation associated with hypoestrogenism. Weight loss, excessive exercise, stress and long-lasting hypoestrogenism lead to infertility and bone loss. FHA also leads to metabolic changes that increase cardiovascular risk in women who otherwise appear metabolically healthy. Methods: This was a case–control study assessing metabolic and endocrine alterations in patients with FHA, stratified by BMI into underweight (BMI < 18.5) and normal-weight (BMI 18.5–24.99) categories. Results: Women diagnosed with FHA had significantly higher levels of total (193 ± 41.96 vs. 181 ± 28.23 mg/dL; p = 0.037) and LDL cholesterol (67 ± 34.89 vs. 63 ± 24.78 mg/dL; p = 0.018) compared with healthy controls. HDL cholesterol levels did not differ between groups; however, normal-weight participants in the study group had higher HDL cholesterol than underweight participants (p = 0.007). FHA patients had significantly lower HOMA-IR (p = 0.001), lower prolactin (p < 0.001), and higher cortisol levels (p = 0.036). Conclusions: Metabolic and endocrine alterations in FHA patients are modulated both by the condition per se and by BMI. FHA influences total and LDL cholesterol, prolactin, and cortisol levels, while BMI primarily affects HDL cholesterol. Both FHA and BMI have a statistically significant impact on HOMA-IR, but neither influences triglycerides or TSH levels. Our findings indicate that the recovery and prevention of metabolic complications require psychological support and consistent weight management. Full article

(This article belongs to the Special Issue Recent Developments in Gynecological Endocrinology)

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14 pages, 1357 KB

Open AccessArticle

The Impact of Polycystic Ovary Syndrome on Mood Disorders: A Cross-Sectional Questionnaire Study on Chronotypes, Social Jetlag, and Night Eating Habits

by Senol Senturk, Mehmet Kagitci, Meltem Pusuroglu, Ugur Avci, Tahsin Gokhan Telatar, Bahar Kefeli Col, Nalan Kuruca, Deniz Dereci Delibas, Safak Hatirnaz, Filiz Mercantepe and Andrea Tinelli

J. Clin. Med. 2025, 14(19), 7068; https://doi.org/10.3390/jcm14197068 - 7 Oct 2025

Cited by 1 | Viewed by 1524

Abstract

Objective: To determine the prevalence of mood and eating disorders, chronotype, and social jetlag in a cohort of women with polycystic ovarian syndrome (PCOS). Methods: A total of 70 patients, 35 with PCOS and 35 healthy controls, aged between 18 and 40 years, were included in the study. PCOS was diagnosed according to the Rotterdam criteria. Five different questionnaires, namely the “Morningness–Eveningness Questionnaire (MEQ)”, “Social Jetlag Status (SJL)”, “Night Eating Questionnaire (NEQ)”, “Beck Depression Inventory (BDI)”, and “Beck Anxiety Inventory (BAI)”, were administered to patients with and without PCOS, and the “total questionnaire scores” of both groups were compared. Results: In addition to BMI (p = 0.004), serum insulin (p < 0.001), HOMAIR (p < 0.001), total testosterone (p = 0.006), DHEAS (p = 0.004), and LH (p < 0.001) levels were significantly higher in women with PCOS than in the controls. BAI (p = 0.006), BDI (p = 0.007), and NEQ (p = 0.013) scores of participants with PCOS were significantly higher than those in the control group, while MEQ scores were significantly lower than those in the control group (p = 0.005). When categorized according to the total test scores, the number of individuals with moderate and severe anxiety was significantly higher in the PCOS group than in the control group (p = 0.030). Morningness was significantly lower in the PCOS group than in the control group, whereas eveningness was higher than that in the control group (p = 0.013). There was no difference between the PCOS and control groups in terms of the number of individuals with SJL ≥ 2 h and night eating disorders. The NEQ score was positively correlated with BAI, BMI, insulin, and HOMA-IR. Both the BDI and BAI scores were positively correlated with BMI, HOMA-IR, and total testosterone levels. Conclusions: PCOS can lead to mood, appetite, and circadian rhythm issues through variations in chronotype. PCOS-related endocrine, metabolic, and adiposity factors influence mood, eating habits, and chronotype disorders. Full article

(This article belongs to the Special Issue Recent Developments in Gynecological Endocrinology)

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17 pages, 1450 KB

Open AccessArticle

Prevalence of Impaired Bone Health in Premature Ovarian Insufficiency and Early Menopause and the Impact of Time to Diagnosis

by Szilvia Csehely, Adrienn Kun, Edina Orbán, Tamás Katona, Mónika Orosz, Tünde Herman, Zoárd Tibor Krasznai, Tamás Deli and Attila Jakab

J. Clin. Med. 2025, 14(12), 4210; https://doi.org/10.3390/jcm14124210 - 13 Jun 2025

Cited by 1 | Viewed by 2999

Abstract

Background/Objectives: Premature ovarian insufficiency (POI) is a leading cause of hypoestrogenism in women under the age of 40 years and is associated with an increased risk of impaired bone health. Early diagnosis and timely hormonal intervention are essential to prevent irreversible bone loss. However, diagnostic delay is not uncommon in clinical practice. Methods: We conducted a retrospective analysis of 168 women diagnosed with POI or early menopause (EM) between 2017 and 2024 at a tertiary gynecological endocrinology unit. Bone mineral density (BMD) and T-score were assessed by dual-energy X-ray absorptiometry (DXA) at the time of diagnosis in 125 patients, of whom 116 had secondary amenorrhea. The interval between the last menstrual period (LMP) and diagnosis was used to assess the impact of diagnostic delay. The patients were further stratified by serum estradiol (E2) levels and body mass index (BMI). Results: At the time of diagnosis, 43.1% of patients had osteopenia, and 10.3% had osteoporosis. A statistically significant negative correlation was observed between time to diagnosis and BMD (r = −0.225, p = 0.022), with a similar trend seen for T-score (r = −0.211, p = 0.031). In patients with E2 ≤ 5 ng/L, the association was stronger (BMD: r = −0.401, p = 0.026). Lower E2 levels tended to be associated with poorer bone health in women with a BMI < 25 kg/m², whereas no such trend was observed in those with a higher BMI. Conclusions: Our findings indicate that diagnostic delay in POI is associated with deterioration in bone health, particularly in lean patients and those with severe hypoestrogenism. These results underscore the importance of early recognition and timely initiation of hormone therapy to preserve bone mass and reduce long-term skeletal complications. Full article

(This article belongs to the Special Issue Recent Developments in Gynecological Endocrinology)

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15 pages, 541 KB

Open AccessArticle

Dietary Patterns and Metabolic and Hormonal Parameters in Women with Suspected PCOS

by Karolina Kowalczyk, Sabina Kadłubek, Aleksandra Krużel, Dominik Sikora, Jakub Daniluk and Paweł Madej

J. Clin. Med. 2025, 14(8), 2708; https://doi.org/10.3390/jcm14082708 - 15 Apr 2025

Cited by 4 | Viewed by 4141

Abstract

Background: Insulin resistance, visceral adiposity, excess body weight, and symptoms of hyperandrogenism often accompanies Polycystic Ovary Syndrome (PCOS). A balanced diet plays a key role in improving the metabolic and biochemical parameters in affected women. This study aims to assess whether dietary improvements in patients with suspected PCOS may affect the severity of the disease and the metabolic and hormonal profile. Methods: The analysis of the relationships between self-declared nutritional changes and biochemical and metabolic parameters included 154 women at the same stage of PCOS diagnosis. Results: Over half of participants reported dietary modifications. Women reducing sweets, fatty red meat, and alcohol intake for >6 months had significantly lower total testosterone (TT) levels compared to those who did not (p < 0.05). Mean TT levels were: 0.375 ± 0.18 ng/mL (median 0.340) vs. 0.787 ± 2.19 ng/mL (median 0.390) for red meat (p = 0.008), 0.359 ± 0.18 ng/mL (median 0.335) vs. 0.681 ± 1.9 ng/mL (median 0.4) for sweets (p = 0.02), and 0.388 ± 0.19 ng/mL (median 0.34) vs. 0.917 ± 2.65 ng/mL (median 0.425) for alcohol (p = 0.004). Patients with dietary changes in the past 6 months had higher androgen levels, BMI, systolic blood pressure and triglycerides than patients with long-term dietary changes (p < 0.05). There were no statistically significant differences in key metabolic and biochemical parameters when comparing self-reported diets based on glycemic index (low vs. high). Conclusions: A healthy, balanced diet for women with PCOS requires a multifaceted approach with clear, defined goals. This leads to better results than broad, general dietary recommendations. Long-term dietary changes improve biochemical and metabolic parameters, but maintaining these benefits requires continuous patient motivation. Full article

(This article belongs to the Special Issue Recent Developments in Gynecological Endocrinology)

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11 pages, 1243 KB

Open AccessArticle

Changes in Prolactin and Insulin Resistance in PCOS Patients Undergoing Metformin Treatment: A Retrospective Study

by Tal Goldstein, Johannes Ott, Paula Katzensteiner, Robert Krysiak, Rodrig Marculescu, Magdalena Boegl and Marlene Hager

J. Clin. Med. 2024, 13(24), 7781; https://doi.org/10.3390/jcm13247781 - 20 Dec 2024

Cited by 3 | Viewed by 2473

Abstract

Background: Prolactin levels have been shown to influence metabolic outcomes, including insulin resistance. Metformin is known to be beneficial in polycystic ovary syndrome (PCOS) patients. PCOS women might react differently to metformin treatment depending on their baseline prolactin levels. Methods: In this retrospective study, the homeostasis model assessment for insulin resistance (HOMA-IR), prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), the LH:FSH ratio, and total testosterone and sex hormone-binding globulin (SHBG) were measured in 75 obese/overweight women with PCOS and insulin resistance before initiation of metformin treatment and after 6–8 months. Results: At baseline, HOMA-IR was inversely correlated to SHBG (r = −0.408; p < 0.001) and prolactin (r = −0.402; p < 0.001). After 6–8 months of metformin treatment, the LH:FSH ratio and the HOMA-IR declined significantly (p < 0.05). A significant positive correlation could be shown between basal prolactin and the difference in the HOMA-IR (r = 0.233; p = 0.044). Women with lower baseline prolactin (≤14.9 ng/mL) revealed a sharper decline in HOMA-IR (−0.8, IQR −1.0; −0.5 vs. −0.6, IQR −0.8; −0.3; p = 0.049) as well as an increase in prolactin at follow-up (1.6 ng/mL, IQR −0.2;3.8 vs. −1.3, IQR −4.6;3.2; p = 0.003) compared to patients with a baseline prolactin > 14.9 ng/mL. Conclusions: In overweight/obese, insulin-resistant PCOS women, lower baseline prolactin levels are associated with higher baseline HOMA-IR levels as well as with a better response to metformin treatment. More data are necessary to prove these observations in larger populations. Full article

(This article belongs to the Special Issue Recent Developments in Gynecological Endocrinology)

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13 pages, 787 KB

Open AccessArticle

Endocrine Characteristics and Obstetric Outcomes of PCOS Patients with Successful IVF and Non-IVF Pregnancies

by Mónika Orosz, Fanni Borics, Dávid Rátonyi, Zoárd Tibor Krasznai, Beáta Vida, Tünde Herman, Szilvia Csehely, Attila Jakab, Luca Lukács, Rudolf Lampé and Tamás Deli

J. Clin. Med. 2024, 13(18), 5602; https://doi.org/10.3390/jcm13185602 - 21 Sep 2024

Cited by 1 | Viewed by 4512

Abstract

Background/Objective: Infertility affects an estimated 40–50% of women with polycystic ovary syndrome (PCOS), the leading cause of anovulatory infertility, but only a small proportion of the patients require in vitro fertilization (IVF) therapy. Both PCOS and IVF are associated with an increased risk of obstetric complications. To compare preconception endocrine profiles and symptoms, as well as obstetric outcomes of PCOS patients who achieved successful pregnancies with and without IVF treatment. Methods: A single-center retrospective cohort study was conducted. Data spanning from 2012 to 2019 were compiled from patients with PCOS who visited the Gynecologic Endocrinology Unit and the Infertility Unit at the Department of Obstetrics and Gynecology, University of Debrecen. Patients diagnosed with PCOS who had had at least one successful delivery beyond the 23rd gestational week at the department were eligible for inclusion in the study. Results: Fifteen percent of the 206 pregnancies leading to successful deliveries of 232 newborns in our cohort conceived with IVF. A one year increase in the maternal age increased the odds of being in the IVF group by 22% (OR: 1.222, 95% confidence interval, CI: 1.11–1.35, p < 0.001). Baseline DHEAS and androstenedione levels were significantly lower in the IVF group as compared to the non-IVF group: 1 μmol/L increase in the DHEAS level decreased the odds of being in the IVF group by 18% (OR: 0.82, 95% CI: 0.66–1.01, p = 0.06), and 1 μg/L increase in the serum androstenedione concentration decreased the same odds by 42% (OR: 0.58, 95% CI: 0.33–1.02, p = 0.056). DHEAS levels <6.5 μmol/L had an OR 3.86 (95% CI 1.10–13.50, p = 0.04) and LH/FSH ratio <1.3 had an OR 3.58 (95% CI 1.18–10.81, p = 0.03) for being in the IVF group. The birth weight (3069 ± 683 g vs. 3362 ± 638 g, p = 0.02) and the gestational age (37.23 ± 2.55 vs. 38.54 ± 2.28 weeks, p = 0.004) were significantly lower in the IVF group, but in the singleton subgroups, no significant differences could be found. Birth weight percentiles showed no significant difference in either subgroup. In the IVF group, both preterm delivery (29% vs. 8.3%, OR 4.53, 95% CI 1.75–11.70, p = 0.002; singleton subgroup: 17.4% vs. 6.3%, OR 3.12, 95% CI 0.89–10.92, p = 0.07) and cesarean section (71% vs. 43.2%, OR 3.22, 95% CI 1.40–7.40, p = 0.006; singleton subgroup: 65.2% vs. 42.4%, OR 2.55, 95% CI 1.02–6.35, p = 0.04) were more frequent than in the non-IVF group. Gestational diabetes and preeclampsia were not significantly different in the IVF and non-IVF groups. Conclusions: In PCOS patients with successful pregnancies, those who conceive with IVF seem to be different in their baseline hormone levels and symptoms from the non-IVF group. Adverse obstetric outcomes are more common in the IVF group, and some of these differences persist when adjusting for singleton pregnancies and maternal age, too. Full article

(This article belongs to the Special Issue Recent Developments in Gynecological Endocrinology)

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Review

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17 pages, 988 KB

Open AccessReview

Estradiol and Micronized Progesterone: A Narrative Review About Their Use as Hormone Replacement Therapy

by Martina Foschi, Giulia Groccia, Maria Laura Rusce, Celeste Medaglia, Claudia Aio, Alessandra Sponzilli, Veronica Setti, Christian Battipaglia and Alessandro D. Genazzani

J. Clin. Med. 2025, 14(20), 7328; https://doi.org/10.3390/jcm14207328 - 16 Oct 2025

Cited by 1 | Viewed by 8020

Abstract

Hormone replacement therapy (HRT) currently represents the first-line treatment to manage and reduce menopausal symptoms. Standard regimens generally combine 17β-estradiol (E2) or conjugated equine estrogens (CEEs) with micronized progesterone (P4) or synthetic progestins. While synthetic progestins ensure endometrial protection against estrogen-induced stimulation of the endometrium, their impact on metabolic, cardiovascular, skeletal, and cognitive systems is heterogeneous and not always beneficial. In contrast, progesterone, as a micronized preparation (P4), allows for more physiological effects because it is chemically identical to endogenous progesterone. This narrative review provides an updated overview of the clinical benefits of HRT regimens based on E2/P4, with a focus on their impact on endometrial thickness, venous thromboembolism (VTE), cardiovascular diseases (CVDs), breast cancer risk, cognitive effects, bone protection, and quality of life (QoL). Full article

(This article belongs to the Special Issue Recent Developments in Gynecological Endocrinology)

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12 pages, 650 KB

Open AccessReview

Kisspeptin and Endometriosis—Is There a Link?

by Blazej Meczekalski, Agata Nowicka, Stefania Bochynska, Aleksandra Szczesnowicz, Gregory Bala and Anna Szeliga

J. Clin. Med. 2024, 13(24), 7683; https://doi.org/10.3390/jcm13247683 - 17 Dec 2024

Cited by 1 | Viewed by 2894

Abstract

This article presents a narrative review that explores the potential link between kisspeptin—a key regulator of the hypothalamic-pituitary-gonadal axis—and the pathogenesis of endometriosis. Kisspeptin plays a significant role in regulating reproductive functions by modulating the release of gonadotropin-releasing hormone (GnRH), which in turn stimulates the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Recent studies suggest that kisspeptin may also impact peripheral reproductive tissues and influence inflammatory processes involved in the development of endometriosis. Altered kisspeptin signaling has been associated with the abnormal hormonal environment observed in endometriosis, which affects menstrual cycles and ovarian function. Research indicates that women with endometriosis exhibit altered levels of kisspeptin and its receptor, KISS1R, in both eutopic and ectopic endometrial tissues, suggesting a role in disease progression, particularly in tissue invasion and lesion formation. Kisspeptin’s role in regulating matrix metalloproteinases (MMPs), enzymes essential for tissue remodeling, further supports its potential contribution to the pathophysiology of endometriosis. Moreover, kisspeptin-based therapeutic strategies are currently under investigation, with the aim of providing targeted treatments that reduce the side effects commonly associated with existing therapies. Despite promising findings, further research is needed to fully understand the mechanisms by which kisspeptin influences endometriosis. Full article

(This article belongs to the Special Issue Recent Developments in Gynecological Endocrinology)

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