Archives of Pharmacy

Biomarkers of menopause

Snežana Jovičić, Mario Plebani — Fri, 21 Feb 2025 00:00:00 +0100

Natural menopause is defined as the permanent cessation of menstruation resulting from the loss of ovarian follicular activity. This significant phase in women’s reproductive aging has notable effects on fat distribution, dyslipidemia, and neurodegeneration. These changes contribute to an increased risk of dementia and cardiovascular disease as women age. Estimating the age at which natural menopause will occur is crucial for cancer survivors, women with a family history of premature ovarian insufficiency or early menopause, and those delaying their first pregnancy. Additionally, the timing of natural menopause is an important clinical indicator of longevity and a risk factor for morbidity and mortality. Beyond age and menstrual cycle characteristics, biomarkers related to menopause are essential for confirming its onset and predicting its premature occurrence.

Osteopororosis and reproductive health

Danijela Ristovski Kornić, Mirela Matejić — Sat, 22 Feb 2025 00:00:00 +0100

Osteoporosis is a prevalent issue among menopausal women; however, the number of women with risk factors across all age groups is increasing. This trend can lead to the development of osteopenia or osteoporosis at a younger age, significantly impacting women’s physical, emotional, and mental well-being. This review aims to evaluate the current literature on the prevalence of osteoporosis and its most common risk factors among women across all age groups. It serves as an updated reference for readers, helping to understand the fundamental pathophysiological mechanisms of the disease, diagnostic methods, and the role of medications and lifestyle in its prevention. Some authors suggest that the dominant mechanism of bone mass loss is slowed osteoblastic bone formation, while others highlight increased breakdown of the bone matrix as the more prominent mechanism of skeletal damage, depending on the underlying cause of osteoporosis. Increased bone fragility and a higher tendency towards pathological fractures significantly impact both the quality of life and life expectancy in women. Therefore, it is recommended that osteological screening and fracture risk assessment become a mandatory component of individualized care for women across all age groups. The focus of women’s bone health care has shifted from postmenopausal treatment to preventative care.

Genetic predisposition for ovarian cancer development

Ivana Joksić, Uršula Prosenc Zmrzljak, Ana Ninić, Tamara Ratković, Jelena Munjas — Sat, 22 Feb 2025 00:00:00 +0100

Ovarian cancer is a leading malignancy in the female reproductive system and is responsible for more deaths than any other type of cancer affecting this system. Ovarian cancers can be hereditary or sporadic. Anatomic, cellular, microenvironmental and molecular features of ovarian cancers show a high degree of heterogeneity. Numerous genes implicated in the pathogenesis and progression of ovarian cancers have been identified to date. The majority of these genes act as tumour suppressor genes, oncogenes, or are involved in mismatch repair and double-strand break repair mechanisms. The identification of mutations in cancer susceptibility genes could be a major step forward towards earlier diagnosis, personalized therapy approaches and outcome monitoring. In healthy women, detecting a specific mutated gene can provide a rationale for personalized surveillance, chemopreventive strategies, and prophylactic surgery. Next-generation sequencing offers comprehensive genome analysis, which enables profound understanding and identification of cancer susceptibility genes, and new molecular diagnostic markers and therapeutic targets.

The role of oxidative stress in male infertility: connection to sperm telomere shortening and overall DNA damage

Biljana Glišić, Jelena Kotur Stevuljević — Sat, 22 Feb 2025 00:00:00 +0100

Male infertility affects approximately 20% of men, with 30–40% of cases being linked to issues in both partners. While sperm production may be normal, DNA damage in spermatozoa can occur and become a primary cause of infertility. The exacerbation of oxidative stress leads to damage to various biomolecules, such as DNA fragmentation, lipid peroxidation, and protein oxidation, all of which can impair egg fertilization and embryo development. Elevated levels of reactive oxygen species (ROS) in semen are associated with poor sperm quality, reduced fertilization potential, and increased sperm DNA fragmentation. Additionally, shorter telomeres in semen correlate with reduced sperm vitality and function. Oxidative stress accelerates telomere attrition by inducing DNA damage, which leads to telomere shortening and potentially compromises sperm function and fertility. DNA damage can occur at different stages of spermatogenesis and fertilization. If the damage surpasses the oocyte’s repair capacity, infertility may occur. Various tests are available to assess sperm DNA damage, with the sperm DNA fragmentation (SDF) test being one of the most promising. DNA damage is quantified as the DNA fragmentation index (DFI), which represents the percentage of spermatozoa with fragmented DNA. Although reference intervals for DFI may vary depending on the method used, DFI ≤ 15% is generally considered normal, 15–30% is considered average, and DFI ≥ 30% indicates poor DNA integrity, which may negatively impact pregnancy outcomes.

Monocyte/HDL-cholesterol ratio as an early prognostic marker of pregnancy complications development

Sat, 22 Feb 2025 00:00:00 +0100

Pregnancy complications increase the long-term cardiovascular risk for both the mother and the child. Inflammation is a common mechanism underlying the development of pregnancy complications and atherosclerosis. This study aims to investigate whether the monocyte/HDL cholesterol ratio can serve as a predictive marker for the risk of pregnancy complications. A total of 84 pregnant women participated in this study, 41 of whom had a normal pregnancy course, while 43 experienced complications. Lipid status parameters were measured using enzymatic methods and total blood count was measured using a hematology analyzer. In the first trimester of pregnancies with complications we observed significantly higher levels of total cholesterol (P < 0.01), low-density lipoprotein cholesterol (LDL-C) (P < 0.01) and triglycerides (P < 0.001) compared to pregnancies without complications, whereas no differences were observed in high-density lipoprotein cholesterol (HDL-C). Pregnant women with complications had a significantly higher proportion of monocytes throughout the entire pregnancy, and lower concentrations of HDL-C in the second trimester (P < 0.05). The risk of developing complications in pregnancy was 11 times higher if the monocyte/HDL-C ratio was elevated in the first trimester (OR: 11.42; 95%CI: 4.05–32.19; P < 0.001). Our results indicate that monocyte/HDL-C ratio could be used as a simple and cost-effective early prognostic biomarker of pregnancy complications.

Enzyme and lipid markers in relation to cardiovascular risk in postmenopausal women

Aleksandra Klisić, Filiz Mercantepe, Mirjana Bakić, Ana Ninić — Sat, 22 Feb 2025 00:00:00 +0100

Postmenopausal women are at an increased risk of cardiovascular disease (CVD), the leading cause of death worldwide, compared with younger women. Gamma-glutamyl transferase (GGT) and high-density lipoprotein cholesterol (HDL-c) are linked with oxidative stress, inflammation, insulin resistance, and CVD risk factors. However, there have been no studies that examined the relationship between GGT/HDL-c and CVD exclusively in women who are not of reproductive age. Therefore, we aimed to examine this potential relationship in a cohort of CVD-free postmenopausal women. A total of 150 disease-free postmenopausal women were consecutively included. CVD risk was defined according to high sensitivity C-reactive protein (hsCRP) concentration (hsCRP < 1 mg/L defines low risk and hsCRP ≥ 1 mg/L defines intermediate and high risk). The GGT/HDL-c was independently associated with intermediate and high CVD risk in postmenopausal women_. As this enzyme/lipid index increased by 1 unit, the probability of intermediate and high CVD risk rose by 10.3% (OR = 1.103, p = 0.024). The GGT/HDL-c ratio was independently associated with higher CVD risk, as measured with hsCRP in postmenopausal women. This cost-effective, easily measured, and widely available index could be used in everyday clinical practice for estimating CVD risk in postmenopausal women.

Association Between Systemic Inflammation and Lipid Metabolism in the Development of Preeclampsia

Sat, 22 Feb 2025 00:00:00 +0100

Preeclampsia (PE) is a pregnancy complication marked by hypertension (≥ 140/90 mmHg) and proteinuria (≥ 300 mg/24 h), with an unclear pathogenesis involving inflammation and dyslipidemia. This study aimed to longitudinally examine changes in lipid status parameters and inflammatory markers in pregnant women at high risk for PE and those who developed PE. Among 91 women, 20 developed PE (PE group), and 71 were high-risk (HR group). Both groups were monitored at four points: T1-first, T2-, T3-third trimester, and T4-pre-delivery. Lipid markers (triglycerides (TG), total cholesterol (TC), HDL-C, LDL-C, apolipoproteins A-I and B-100) and inflammatory markers (high-sensitivity C-reactive protein (hsCRP), resistin, serum amyloid A (SAA), and macrophage chemotactic protein-1 (MCP-1)) were assessed. Results showed significantly higher TG, resistin, and MCP-1 concentrations in the PE group compared to the HR group at T1 (p < 0.05, p < 0.01, p < 0.01, respectively). During pregnancy, both groups exhibited increases in TG, TC, LDL-C, SAA, and MCP-1 (p < 0.001), while HDL-C and resistin increased only in the HR group (p < 0.001). PE development is associated with atherogenic lipid changes, characterized by hypertriglyceridemia and no increase in HDL-C, with elevated SAA potentially diminishing HDL’s protective role.