Current Pharmaceutical Design - Volume 27, Issue 36, 2021

Preterm delivery represents the major cause of neonatal morbidity and mortality. Respiratory morbidity is the primary cause of early neonatal mortality and disability. The administration of antenatal corticosteroids, in cases of imminent preterm delivery, can enhance fetal lung maturation and reduce the incidence of respiratory distress syndrome, leading to improved neonatal outcomes. The scope of this narrative review was to synthesize available evidence on the efficacy and safety of corticosteroids' administration during antenatal period, in cases of anticipated preterm delivery. Hence, for those cases, a single course of antenatal corticosteroids from 24 up to 34 gestational weeks should be offered. Betamethasone and dexamethasone are the most widely used drugs, with similar effectiveness and a recommended dosage of 24mg in divided doses, over a 24- hour period. However, there is an ongoing debate regarding the gestational age of administration. Some obstetric societies recommend their administration even at 22 weeks of gestation. Conflicting is also their usefulness in late preterm cases (between 34 and 37 weeks) or in cases of elective cesarean delivery at term. The use of repeated courses of corticosteroids may be considered in specific cases, however, concerns on the long-term outcomes of repeated courses beyond 34 gestational weeks have been raised.

Background: Female sexual dysfunction (FSD) has been largely underdiagnosed and undertreated due to the lack of concrete definitions, validated assessment methods and efficient treatments. However, during the last few decades, there has been great progress in the clinical management and research of FSD. Objective: The purpose of this review is to describe the pathophysiology of FSD, report the prevalence of the disease in the setting of cardiovascular (CV) risk factors and disease, and review current and under investigation treatment options. Methods: A comprehensive review was performed to identify studies examining the association of FSD with CV risk factors and/or disease, as well studies reporting relevant management options. Results: The prevalence of FSD is increased in the general population (approximately 40%) and is significantly higher in patients with hypertension, diabetes mellitus, and dyslipidemia. In patients with overt CV disease, FSD is even more prevalent (up to 90%). The cause of FSD is multifactorial and includes a variety of vascular, hormonal, interpersonal and psychological factors, which are all intertwined. Several treatment options exist that are efficient in improving female sexual function, while a cluster of other options has been shown to offer benefits. Conclusion: FSD is a major public health problem with great impact on the patients’ quality of life. In the setting of increased CV burden, FSD is even more prevalent. Increased awareness is needed for the physician to establish a trustful environment with the patient, discuss such issues, and offer proper management options.

Viral hepatitis in pregnancy constitutes a complex issue, requiring meticulous management due to the potential potent compromise of both mother’s and fetus’ health. Hepatitis B and C are implicated with a high risk for chronicity, whereas hepatitis A and hepatitis E have an acute course. In pre-existing viral disease, pregnancy may lead to exacerbation of the disease’s course due to a plethora of hormonal, immunological and genetic alterations. Vice versa, viral hepatitis, acute or chronic, during pregnancy, can cause gestational complications that may lead to significant maternal and neonatal morbidity and mortality. Mother to child transmission of hepatitis B and C virus, in high prevalence areas, has been recognized as a major cause of chronic viral infection and related complications in children. Due to the physiologic alterations in pregnancy, therapeutic indications may differ from those in the general population and there is an expanding field of research on available drugs and vaccines efficacy and safety during pregnancy. Of utmost importance remains the implementation of a preventive strategy in order to reduce the rates of vertical transmission. Universal screening of pregnant women, assessing the risk of transmission and determining the mode of delivery and the impact of breastfeeding are crucial aspects of this strategy. This review summarizes the impact of viral hepatitis in pregnancy, strategies of prevention of vertical transmission and available treatments.

Metabolic syndrome (MetS) represents a cluster of metabolic disorders that arise from insulin resistance (IR) and adipose tissue dysfunction. As a consequence, there is an increased risk for type 2 diabetes mellitus and atherosclerotic cardiovascular disease (CVD). MetS is associated with a 2-fold increase in cardiovascular outcomes. Earlier population analyses showed a lower prevalence of MetS in women (23.9%) in comparison to men (27.8%), while later analyses suggest significantly reduced difference due to an increase in the prevalence in women aged between 20 and 39. However, the prevalence of MetS in specific populations of women, such as in women with polycystic ovary syndrome, ranges from 16% to almost 50% in some geographical regions. Abdominal fat accumulation and IR syndrome are recognized as the most important factors in the pathogenesis of MetS. After menopause, a decline in insulin sensitivity corresponds to an increase in fat mass, circulating fatty acids, low-density lipoproteins, and triglycerides. Prevalence of MetS in acute coronary syndrome (ACS) is significantly more present in women (55.9%-66.3%) than in men (40.2%-47.3%) in different cohorts. Younger women with ACS had a higher mortality rate than younger men. Acute myocardial infarction (AMI) remains a leading cause of death in aging women. Women with AMI had significantly higher rates of prior congestive heart failure, hypertension history, and diabetes. The role of androgens in CVD pathogenesis in women has not yet been clarified. The current review aims to provide an insight into the role of MetS components and inflammation for the development of atherosclerosis, CVD, and AMI in women.

Background: Hypertension of pregnancy [office blood pressure (BP) levels≥140/90 mmHg] is fairly common and can affect up to 10% of pregnant women worldwide. Hypertension of pregnancy is an important risk factor for the mother and carries increased morbidity and mortality for the fetus. Women with hypertension of pregnancy have a high-risk for future cardiovascular and renal events. Objectives: To summarize the literature related to several clinical aspects of hypertension in pregnancy and draw clinically meaningful conclusions. Methods: We conducted an in-depth review of the literature to retrieve existing data on the definition, epidemiology, classification, and management of hypertension in pregnancy. Results: All pregnant women with hypertension should have a proper diagnostic workup and be treated appropriately. In women with mild hypertension, BP therapeutic target should be set to 110-140/80-85mmHg. In women with severe hypertension, BP should be reduced by at least 25% as soon as possible, and gradually thereafter to normal target levels of <140/105mmHg. In terms of preeclampsia, physicians need to consider potential complications and formulate prevention strategies. The choice of antihypertensive medication is crucial since certain classes can be detrimental to the fetus and should be avoided. Post-partum, the choice of antihypertensive therapy of the mother should take into consideration breastfeeding of the fetus. Given the life-long cardiovascular risk of women with pregnancy hypertension, a regular cardiovascular evaluation is in order. Conclusion: Albeit the antihypertensive treatment exerts significant benefits for both the mother and the baby, several clinical aspects remain un-tackled. More research is needed to further improve the treatment of such disorders.

Dyslipidemia represents a major risk factor for cardiovascular disease. In addition, severe hypertriglyceridemia is an important cause of acute pancreatitis. Accordingly, the increase in serum lipid levels that is observed during pregnancy has potentially important implications. The management of dyslipidemia in pregnancy is further complicated by the lack of safety data during this period for most of the lipid-lowering agents. In the present review, we discuss the most important lipid disorders in pregnant women and their management. Pregnancy is characterized by increases in both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, which might result in severe complications both for the mother and the fetus. Accordingly, LDL-C and triglyceride levels should be monitored during pregnancy, particularly in women with a history of dyslipidemia. Diet is the mainstay of management of dyslipidemia in pregnant women and apheresis can also be considered in patients with homozygous familial hypercholesterolemia or severe hypertriglyceridemia. However, there is a pressing need for studies that evaluate the safety of lipid-lowering agents during pregnancy.

It is well-established that adults with polycystic ovary syndrome (PCOS) have an increased prevalence of several cardiometabolic risk factors, including obesity, insulin resistance, type 2 diabetes mellitus, and dyslipidemia. Accumulating data suggest that these risk factors are already present in adolescence in patients with PCOS. This has major implications for the management of this population since the timely identification of these risk factors is essential for preventing cardiovascular disease in adulthood. The present review summarizes the existing evidence regarding the prevalence of traditional and non-traditional cardiometabolic risk factors in adolescents with PCOS.

Polycystic ovary syndrome (PCOS) is a frequent endocrine disease in women during the reproductive period. It is considered a complex metabolic disorder with long-term metabolic, as well as reproductive consequences. Main pathophysiological pathways are related to the increased androgen levels and insulin resistance. Nowadays, genetic origins of PCOS are acknowledged, with numerous genes involved in the pathogenesis of hyperandrogenemia, insulin resistance, inflammation, and disturbed folliculogenesis. Rotterdam diagnostic criteria are most widely accepted and four PCOS phenotypes have been recognized. Metabolic abnormalities are more common in phenotypes 1 and 2. Women with classic PCOS are more obese and typically have the central type of obesity, more prevalently displaying dyslipidemia, insulin resistance, and metabolic syndrome that could be associated with an increased risk of cardiovascular complications during life. Heterogeneity of phenotypes demands an individualized approach in the treatment of women with PCOS. Metabolic therapies involve a lifestyle intervention followed by the introduction of insulin sensitizers including metformin and inositols, glucagon-like peptide 1 receptor agonists (GLP-1 RA), as recently sodium-glucose cotransporter-2 (SGLT2) inhibitors. The addition of an insulin sensitizer to the standard infertility therapy such as clomiphene citrate improves ovulation and pregnancy rates. Our current review analyzes the contemporary knowledge of PCOS etiology and etiopathogenesis, its cardiometabolic risks and their outcomes, as well as therapeutic advances for women with PCOS.

Uterine fibroids (leiomyomas or myomas) are the most frequent benign tumors in women. Heavy menstrual bleeding with resultant anemia, dysmenorrhea, chronic pelvic pain, infertility, urinary symptoms and constipation are generally associated with uterine fibroids (UFs). Although strategies mainly resort to surgical intervention, medical treatments are considered the first-line treatment to preserve fertility and avoid surgery. The aim of this review is to offer available and the newest medical treatment options for symptomatic UFs. Various medical therapies are now available for women with uterine fibroids, although each therapy has its own advantages and disadvantages. Our topic specifically explores gonadotropin-releasing hormone (GnRH) analogs and selective progesterone receptor modulators (SPRMs), but also provides the reader with useful advice on the therapies for fibroids available after the recent European Medicines Agency (EMA) warning (EMA/160220/2020). The treatment options depend on the personal treatment objectives of the patients, in addition to treatment effectiveness and necessity for recurrent interventions.

Gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy and is defined as glucose intolerance that first emerges or is first recognized during pregnancy. Several factors increase the risk of a pregnant woman developing gestational diabetes mellitus, and several interventions have been tested for the prevention of GDM development. The most common pharmacological interventions that have been assessed are metformin administration, probiotics administration, and vitamin D administration. However, no intervention appears to be universally superior to placebo/no intervention for the prevention of GDM. Administration of insulin is the preferred medication for treating hyperglycemia in gestational diabetes mellitus. Metformin and glyburide are not regarded as first-line agents, as both cross the placenta to the fetus. Even though there are sufficient data indicating that administration of metformin is safe and effective in women with GDM, there are very limited data concerning the long-term effects of metformin on the offspring. Furthermore, glyburide should be used with caution, as it increases the risk of neonatal hypoglycemia. Some studies also show that it increases the risk of macrosomia. Overall, oral agents may be a therapeutic option in women with GDM after a discussion of the known risks and the need for more long-term safety data in the offspring. The present review aims to highlight the current scientific status regarding the prevention and treatment of GDM.