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BACKGROUND: Vasomotor symptoms (VMS) affect 70% of menopausal women and are considered as hallmark symptoms of the menopausal transition experienced by over three quarters of women and severely by 25% of women. Estrogen withdrawal alone is not fully responsible for the onset of the menopausal vasomotor symptoms and the mechanism of altered thermoregulation appears to be centrally mediated with alterations in hypothalamic neurotransmitters playing a key part. The loss of thermoregulatory control coexists with the altered Kisspeptin- Neurokinin B-Dynorphin-expressing (KNDy) neurons of the arcuate nucleus signaling triggered by menopause. OBJECTIVE: Aim of the review was to explore evidence-based non-hormonal pharmacological interventions for treating vasomotor symptoms. METHODS: Comprehensive overview of relevant literature. CONCLUSIONS: In the population where, hormonal options are contraindicated or not preferred by the patient, it is essential to explore evidence-based non-hormonal pharmacological interventions for treating vasomotor symptoms. The 2024 landscape of available treatments has expanded yet again, arming the providers with an even wider range of possibilities to help their patients. Fezolinetant, is the first NK3R antagonist developed for the purpose of treating hot flashes in menopausal women. NK3R antagonists provide a safe and effective treatment option for managing menopausal women with VMS.

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The current global COVID-19 mortality rate is estimated to be around 3.4%; however, it is dependent on age, sex, and comorbidities. Epidemiological evidence shows gender disparities in COVID-19 severity and fatality, with non-menopausal females having milder severity and better outcomes than age-matched males. However, the difference vanishes when comparing postmenopausal women with age-matched men. It has been suggested that, to some extent, this is due to the protective role of female hormones, such as anti-Müllerian hormone and oestradiol (E2), in non-menopausal women. Oestrogens have been hypothesized to be crucial in modulating viral infection and the progression of the disease via an action on immune/inflammatory responses and angiotensin-converting enzyme type 2 expression. Hence, the most likely explanation is that, because the levels of oestrogen in females after menopause decrease, oestrogen no longer offers a beneficial effect as seen in younger females. The COVID-19 pandemic has highlighted the serious negative effects arising from the state of E2 deficiency. Therefore, hormone replacement therapy gains further support as the damaging effect of the decline in ovarian function affects many biological systems, and recently with the COVID-19 pandemic, oestrogen's vital role within the immune system has become quite clear. However, additional clinical investigations regarding hormone replacement therapy are urgently needed to further verify the protective and therapeutic effects of E2 on menopausal women with COVID-19.

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Menopause is one of the most important events in the female reproductive life cycle, being a transition from the reproductive to the nonreproductive stage. It is a milestone that may have a negative influence on quality of life and one that brings in several physiological changes that affect the life of a woman permanently. According to a Polish epidemiological forecast, in 2050 the average female life expectancy will be 87.5, which is 6.4 years longer than today. Thus, the life expectancy of women who will be 60 or older in 2050 will also extend. Therefore, strategies need to be optimized to maintain postreproductive health, in part because of increased longevity. The general gynecologist can expect to see more elderly female patients as the population continues to age. Office management of the gynecologic problems of geriatric women requires sensitivity to the special needs of this group. Nowadays, most women spend more than one-third of their lives after menopause; therefore there is plenty of opportunity for gynecologists to cater to the needs of postmenopausal women. It is in their scope of practice to help postmenopausal women through "healthy aging". In this review we look into screenings, early identification, lifestyle modifications and appropriate intervention that may prevent many chronic conditions that cause morbidity and mortality during the postmenopausal years.

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Metabolic disorders occurring in menopause, including dyslipidemia, disorders of carbohydrate metabolism (impaired glucose tolerance - IGT, type 2 diabetes mellitus - T2DM) or components of metabolic syndrome, constitute risk factors for cardiovascular disease in women. A key role could be played here by hyperinsulinemia, insulin resistance and visceral obesity, all contributing to dyslipidemia, oxidative stress, inflammation, alter coagulation and atherosclerosis observed during the menopausal period. Undiagnosed and untreated, metabolic disorders may adversely affect the length and quality of women's life. Prevention and treatment preceded by early diagnosis should be the main goal for the physicians involved in menopausal care. This article represents a short review of the current knowledge concerning metabolic disorders (e.g. obesity, polycystic ovary syndrome or thyroid diseases) in menopause, including the role of a tailored menopausal hormone therapy (HT). According to current data, HT is not recommend as a preventive strategy for metabolic disorders in menopause. Nevertheless, as part of a comprehensive strategy to prevent chronic diseases after menopause, menopausal hormone therapy, particularly estrogen therapy may be considered (after balancing benefits/risks and excluding women with absolute contraindications to this therapy). Life-style modifications, with moderate physical activity and healthy diet at the forefront, should be still the first choice recommendation for all patients with menopausal metabolic abnormalities.

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INTRODUCTION: Despite the undeniably positive effect on the quality of life of menopausal women, menopausal hormone therapy (HT) also has negative side-effects, which include, among others, thromboembolic complications. OBJECTIVE: To assess the effect of a popular type of this therapy - transdermal HT on platelet hemostasis, which plays a significant role in intravascular coagulation. MATERIALS AND METHOD: The study group consisted of 92 postmenopausal women: 1) group G1 (n=30), treated with transdermal HT (17ß-estradiol 50 µg/day plus NETA 170 µg/day); 2) group G2 (n=31), treated with the above transdermal HT and low dosage of acetylsalicylic acid (ASA); 3) control group P (n=31). All the women qualified for the study had two or more risk factors for arterial thrombosis, such as: smoking, hypertension, visceral obesity, hypercholesterolaemia, hypertriglyceridaemia, elevated levels of PAI-1, and increased fibrinogen, increased activity of coagulation factor VII. RESULTS: After three months of therapy, in the G1 group there was a decrease in platelet count (p = 0.004) and a decrease in GP IIb/IIIa - a platelet receptor for fibrinogen (p = 0.022). In the G2 group, no changes in the tested parameters were observed. CONCLUSIONS: 1) Transdermal HT in the form of combined, estrogen-progestogen patches favourably modifies platelets haemostasis, reversing the adverse effects that occur after menopause. 2) The use of low ASA doses as a thromboprophylaxis in short-term transdermal HT is not necessary.

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The prognostic value of the MDM2 gene amplification/expression in many types of cancer remains unclear. Polymorphisms in the promoter region of the MDM2 gene have been shown to alter the protein expression and thus, may play a role in carcinogenesis. The aim of the present study was to evaluate the association between the risk of endometrial cancer and SNP309 polymorphisms in the MDM2 gene. The genotype analysis of SNP309 MDM2 gene polymorphisms in 152 endometrial cancer patients and 100 controls of cancer-free subjects, in the Polish population, was performed using the PCR-based restriction fragment length polymorphism (PCR-RFLP). In the presented study, an association between MDM2 SNP309 polymorphisms and the incidence of endometrial cancer was identified. Our results obtained for the SNP309 polymorphisms of the MDM2 gene indicated that both the G/G genotype and the G allele are strongly associated with endometrial cancer. We did not observe any relationship between gene polymorphism and endometrial cancer progression assessed by FIGO grade. This is the first study linking single nucleotide polymorphisms of the MDM2 gene with endometrial cancer incidence in the population of Polish women. The results support the hypothesis that the SNP309 polymorphism of the MDM2 gene may be associated with the incidence of endometrial cancer in the female population.

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OBJECTIVES: Guidelines recommend using the lowest effective dose of oestrogen for the management of vasomotor symptoms in postmenopausal women. The primary aim of this double-blind, multi-centre, randomised study was to assess the efficacy of oral ultra-low dose continuous combined hormone replacement therapy with 17ß-oestradiol and dydrogesterone. STUDY DESIGN: 313 women with ≥50 moderate to severe hot flushes during the previous week were randomised to 0.5 mg 17ß-oestradiol/2.5 mg dydrogesterone (E 0.5 mg/D 2.5 mg), 1mg 17ß-oestradiol/5mg dydrogesterone (E 1mg/D 5 mg) or placebo for 13 weeks. The placebo group then switched to E 0.5 mg/D 2.5 mg for a further 39 weeks, whilst the other groups continued on the same treatment. RESULTS: After 13 weeks, the reduction in the number of moderate to severe hot flushes/day in the E 0.5 mg/D 2.5 mg group was greater than in the placebo group (-6.4 vs. -4.9, p<0.001) and comparable to that in the 1/5 mg group (-6.3). E 0.5 mg/D 2.5 mg and E 1mg/D 5 mg significantly improved the total Menopause Rating Scale score. The number of bleeding/spotting days was lower with E 0.5 mg/D 2.5 mg than with E 1 mg/D 5 mg. The overall amenorrhoea rate with E 0.5 mg/D 2.5 mg was 81%; this increased to 91% in months 10-12. CONCLUSIONS: Continuous combined 0.5 mg 17ß-oestradiol and 2.5mg dydrogesterone was effective in alleviating vasomotor symptoms and improving quality of life, and was associated with a high amenorrhoea rate and a good tolerability profile.

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PURPOSE: Breast cancer is one of the major killers worldwide. Aberrant double-stranded break (DSB) repair leads to genomic instability, which is a hallmark of malignant cells. Double-stranded breaks are repaired in two pathways: homologous recombination (HR) and non-homologous DNA end joining (NHEJ). It is not known whether these repair pathways are affected in sporadic breast tumours. MATERIAL AND METHODS: In the present work the distribution of genotypes and frequency of alleles of the Ku70, A46922G (rs132793) polymorphism and Ligase IV, A6008G (Ile591Val) (rs2232641) polymorphism in breast cancer women were investigated. The genetic polymorphism analysis was performed using a DNA ABI PRISM 377 sequence detection system (Applied Biosystems) in 135 sporadic breast cancer cases. RESULTS: The distribution of the genotypes of the A46922G polymorphism of Ku70 in patients differed significantly (p < 0.05) from those predicted by the Hardy-Weinberg equilibrium. There were significant differences in the frequencies of alleles between the breast cancer subjects and controls (p < 0.05). However, the distribution of the genotypes of the A6008G polymorphism of Ligase IV in both controls and patients did not differ significantly (p > 0.05) from that predicted by the Hardy-Weinberg distribution. CONCLUSION: The results support the hypothesis that the A46922G polymorphism of the Ku70 gene may be associated with the incidence of breast cancer in women from the Lodz region of Poland.

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UNLABELLED: Pelvic organ prolapse is one of the most common disorders and it concerns over 50% of women over the age of fifty who gave birth. BACKGROUND: The purpose of this study was to establish a clinically useful protocol of MR investigation in the assessment of pelvic organs position changes during rest and in time of Velsalva test OBJECTIVE: The material includes 17 postmenopausal women (48- 59-years-old) who were examined due of lumbosacralis discopathy in MR division of USK 1 in Lodz since 2007. The examination was extended to pelvic organs imaging with the help of Velsalva test. RESULTS: Having compared static and dynamic images of investigated group and results of reference lines measurements, we have found normal pelvic organ position comparing to the H line in case of 10 women, in case of 5 women there was just a small displacement--up to 2 cm under the H line--and in case of 2 other women 2 cm above the H line. We have also found substantial increase of P line length (over 25% during tenesmus) in women with pelvic floor disorders. CONCLUSION: Dynamic MR imaging proves extremely useful in evaluation of pelvic organs position changes during rest and in time of Velsalva test.

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UNLABELLED: Estrogens play a crucial role in the pathogenesis and progression of breast and endometrial cancer. The gene ER-alpha is polymorphic and gene variability could contribute to the level of protein biosynthesis. In the present work the distribution of genotypes and frequency of alleles of the Pvull polymorphism and Xbal polymorphism of ER-alpha gene in subjects with breast cancer were investigated. MATERIAL AND METHODS: Blood samples were obtained from 103 postmenopausal women with breast cancer. The polymorphisms were determined by PCR-RFLP. RESULTS: The distribution of the genotypes of Pvull and Xbal polymorphism of ER-alpha in both control and patients did not differ significantly (p > 0.05) from those predicted by the Hardy-Weinberg distribution. There were no significant differences (p > 0.05) in genotype distributions and allele frequencies between subgroups assigned to histological stage. CONCLUSIONS: The results suggest that the Pvull polymorphism of ER-alpha gene as well as Xbal polymorphism may not be linked with appearance and development of breast cancer.

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The group of experts representing the Polish Cardiologic Society, the Polish Gynecological Society and the Polish Menopause and Andropause Society has issued this Joint Position Statement based on the review of available literature on the effect of postmenopausal hormone replacement therapy on the cardiovascular system. The results of older clinical and epidemiological studies are confronted with the most recently published data. The importance of type, doses and delivery route of hormones is discussed with respect to the cardiovascular safety of HRT.

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Reduced DNA repair capacity can render a high risk of developing many types of cancer; including breast cancer. Polymorphisms in DNA repair genes may contribute the genetic instability and carcinogenesis. In the present work the distribution of genotypes and frequency of alleles of the Ser326Cys polymorphism of hOGG1 gene in breast cancer women were analysed. Blood samples were obtained from 100 women with breast cancer and control (n = 106). The polymorphism was determined by PCR-RFLP methods. No association between Ser326Cys polymorphism of hOGG1 and breast cancer risk was observed. The distribution of the genotypes of the Ser326Cys polymorphism in both control and patients did not differ significantly (p > 0.05) from those predicted by the Hardy-Weinberg distribution. There were no significant differences (p > 0.05) in genotype distributions and allele frequencies between subgroups assigned to histological stage. The results suggest that the Ser326Cys polymorphism of hOGG1 gene may not be linked with appearance and development of breast cancer in polish women.

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The aim of the study was to present a new EIN classification of premalignant endometrial lesions. The diagnosis of precancerous disease of the endometrium remains non-standardized because the most widely used World Health Organisation classification is a poorly reproducible system, which does not specify objective architectural criteria for each category of hyperplasia and does not correspond to an appropriate clinical management (undertreatment, overtreatment of the lesions). The new proposed EIN diagnostic schema, based on integrated morphological, genetic molecular, objective histomorphometric (D-score) and clinical outcome studies, divides endometrial lesions into three categories: benign hyperplasia, endometrial intraepithelial neoplasia, and cancer.

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Menopausal period induces some hormonal changes in female organism. These alterations are responsible for many illnesses and ailments - e.g. disorders of menstrual cycle, climacteric symptoms, urine incontinence, connective tissue lesions, postmenopausal osteopenia and osteoporosis. All the changes negatively influence quality of life of women. The principal element of menopausal care in this period is hormone therapy (HT), alleviating many of the climacteric aliments. This article is focused also on some controversial topics concerning the HT action on breast, coronary system and brain.

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Mutations in the MMAC/PTEN (phosphatase and tensin homologue deleted on chromosome 10) gene are documented in cancers of the breast, prostate, ovary, colon, melanoma, glioblastoma, lymphoma and endometrium. In the present work MMAC/PTEN gene expression in women with endometrial adenocarcinoma (n=70) in RNA samples obtained from cancer tissue were investigated. Control DNA was obtained from 68 normal endometrial tissue. The MMAC/PTEN expression was determined by RT-PCR analysis. The expression of MMAC/PTEN gene in endometrial adenocarcinoma cases was significantly reduced compared to the expression in the normal samples (P < 0.05). Furthermore the significant difference (P < 0.05) was observed between the expression of MMAC/PTEN in stage III versus lower stages of endometrial cancer. The results support the hypothesis that the MMAC/PTEN gene expression may be associated with the incidence of endometrial cancer.

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UNLABELLED: One of the reasons for not commencing or withdrawal of HRT in women is their fear for breast and endometrial cancers. Does ultrasonographic valuation guarantee sufficiently patient's safety? Most investigators do not recommend further endometrial diagnostics with endometrial thickness less than 4 mm. Endometrial biopsy is advised in cases of irregular uterine bleedings with normal endometrial image or when any endometrial pathology is suspected. In Poland the most frequently performed procedure of endometrial diagnostics is D&C. Our proposition was to offer endometrial biopsies to all patients who were taken HRT for more than 5 years or, despite having strong climacteric ailments, refused to take it because of their cancerophobia. AIM OF STUDY: To evaluate the usefulness of aspiration endometrial biopsy in women after menopause qualified for HRT. MATERIAL AND METHODS: In 84 females, being postmenopausal (amenorrhoeic for at least 12 months) and qualified for HRT, aspiration endometrial biopsies were performed in outpatient clinics. Age of women ranged 46-63 years, mean 57.3. Attained results were compared to ultrasonographic endometrial evaluation. Such factors as patient's age, menopausal age (years from last menstrual period) and previous administration of HRT were taken into our account (maintaining a 3-month wash-out interval). In 74% of women we have got a material being sufficient for histological evaluation. Form clinical point of view the most important for us was to exclude a proliferative or neoplastic process within endometrium. One of endometrial polyps was omitted in USG study, we were surprised also while detecting endometrial carcinoma cells in endometrium below 3.5 mm. In one postoperative slide the cells of endometrial ovarian carcinoma (with infiltrated Fallopian tube) were detected. CONCLUSION: Endometrial biopsy seems to be a useful, effective and cheap method of endometrial diagnostics also in women after menopause.

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Apoptotic cell death plays a central role in the pathogenesis and disease progression of cancer as well as in the response to treatment. In the present work we investigated the association between the presence of apoptotic peripheral blood cells in breast and ovarian cancer progression. Apoptosis was analysed in blood cells of breast (n=82) and ovarian cancer patients (n=79). Blood samples from age matched healthy women served as control (n=70). The apoptotic peripheral blood cells were detected by agarose gel electrophoresis. The apoptotic cells were identified in 83% (68/82) of the breast cancers and in 65% of ovarian cancer patients (51/79). The number of positive samples was significantly higher among cancer samples than among control samples (p<0.05). Additionally, there were significant differences (p<0.05) in the presence of apoptosis between subgroups assigned to histological stage. The high frequency of apoptotic peripheral blood cells in breast and ovarian tumours suggests a potential role of apoptosis in cancer appearance and/or progression.

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