ACTA ENDOCRINOLOGICA (BUC)

Endocrine disruptors (EDs) are considered to have an impact on the function of reproductive axis at different levels as well on reproductive organs in both sexes. Complexity of female reproductive system influenced with various stressors including EDs lead to morphological and functional alterations. This is resulting in modulation of neuroendocrine regulation with consequent developmental irregularities and derangements, causative infertility, endometriosis as well as premature ovarian insufficiency or polycystic ovary syndrome. A number of experimental clues was obtained on female animal models using various EDs such as synthetic estrogens and phytoestrogens, neurotransmitters, pesticides or various chemicals. These substances lead towards consequent derangement of the neuroendocrine control of reproduction from early phases of reproductive development towards different phases of adult reproductive period. This text will address some novel insights into the effects of EDs on neuroendocrine regulation of gonadal axis, effects on ovaries as well on endometrium during implantation period.

Objectives. The present paper aims to investigate the effects of both progesterone and progestin treatment mainly related to the occurrence of breast cancer in women. Materials and methods. Extensive systematic bibliographic review of Greek and International articles was conducted through the electronic databases Pubmed, Cinahl, Uptodate, and Google Scholar for the identification of articles related to progesterone, progestins and breast cancer treatment. Results. Hormone therapy with the use of estrogen alone presents a small increased risk or does not present at all an increased risk of breast cancer. With ORs in some studies below 1.0 in current users for 3 plus years and safe option until 7 years, while in other studies the risk was increased with the ORs 1.29. However, the use of estrogen in combination with progestogens, depending on the type of progestogens, shows an increased risk of breast cancer, with the ORs to vary between 1.14- 2.38 from 3 to 5 years and is inversely proportional to the time of its use. This risk varies depending on the combination of the preparations. Other factors that are associated with breast cancer risk when receiving hormone therapy are the years that hormone therapy is taken, directly proportional to the risk. At higher risk are older women, women with low body mass index in menopause (BMI <25kg/m2) and women with increased mammographic breast density. Continued use of hormone therapy is associated with an increased risk for breast cancer compared to sequential. The risk became visible sooner to women who used in the past hormone therapy and were using it again. Starting hormone therapy in the immediate postmenopausal period also increased the risk for breast cancer. Hormone therapy was associated with tumors with positive estrogen and progesterone receptors, and also the lobular histological type was associated with its use. Tibolone use was associated with an increased risk.

Aim. The purpose of this study was to examine various hormonal, biochemical and environmental factors (i.e., smoking and alcohol intake) and to investigate their possible correlation to the development of polycystic ovary syndrome (PCOS). The main objective was to evaluate the associations between hormonal profile and the antimüllerian hormone (AMH) levels in PCOS patients and their relation to environmental factors. Patients and Methods. In two gynecological clinics, 38 women with PCOS (defined according to the Rotterdam criteria) were enrolled and observed in relation to AMH, follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), Δ4-androstendione (Δ4- A), dehydroepiandrosterone sulfate (DHEA-S) and glucose plasma concentrations. Obesity, smoking and alcohol exposure were also studied. Results. AMH, T, Δ4-Α, DHEA-S, LH and FSH were increased in 76.3%, 50%, 31.8%, 23.7%, 21% and 18.4% of the patients, respectively. The LH/FSH ratio and glucose concentrations increased abnormally in 18.4% and 15.8% of the patients, respectively. AMH and T levels were both increased in 47.4% of the patients whereas both AMH and LH levels increased in 21% of the patients. Smoking, alcohol intake, obesity and glucose concentrations were not associated with AMH concentrations. On the contrary, high levels of T and LH were linked to higher levels of AMH. FSH concentrations were not increased in these patients. Conclusion. AMH is an important hormonal parameter for the diagnosis of PCOS. Larger clinical controlled studies are necessary in an effort to further investigate the inclusion of AMH measurement in the diagnostic criteria of PCOS.

Context. Cardiovascular risk is increased in women with polycystic ovary syndrome (PCOS). Do insulin sensitizing agents such as metformin (MET) and myoinositol (MI) ameliorate biomarkers of cardiovascular risk? Objective. To compare the effects of MET and MI on blood pressure, lipid profile and high sensitive C-reactive protein (hs-CRP) in women with PCOS in respect to their body mass index (BMI). Design. Open label, parallel randomized, single center study. Subjects and Methods. Sixty six women with PCOS (33 normal-weight and 33 overweight/obese) were randomized to either MI (4 g/day) or MET (1500 mg/day) for a period of 6 months. Serum concentration of hormones, lipid profile, oxidized LDL (ox-LDL), hs-CRP, blood pressure measurement and clinical assessment of BMI, waist circumference (WC) and Ferriman Gallwey score (FG score) were performed before and after treatment. Results. Thirty patients in each group completed the trial. Compared with MET, MI significantly decreased diastolic blood pressure (DBP) (p=0.036) and significantly increased serum hs-CRP (p=0.043). No differences between groups in total cholesterol (TC), HDL-cholesterol, LDLcholesterol, ox-LDL and triglycerides were reported after 6 months. Treatment with MI reduced BMI (p=0.037), WC (p=0.005), DBP (p=0.021) and TC (p=0.008). During MET treatment a significant decrease in BMI (p=0.005), WC (p=0.004), FG score (p=0.001), testosterone (p=0.013) and free androgen index (FAI) (p=0.006) was observed. Conclusions. Our study showed an advantage of MI in reduction of DBP and TC thus predicting favorable metabolic and cardiovascular outcomes in PCOS women. MET more effectively decrease indices of hyperandrogenism.

Contraceptives are widely used in our times and a lot of research has been conducted to clarify their impact on Bone Mineral Density. Combined Oral Contraceptives (COCs) may be detrimental to the BMD of adolescents. However, low-dose are more protective than ultra-low-dose COCs. When it comes to premenopause and perimenopause, COCs have no impact on BMD in women with good ovarian function and no estrogen deficiency. In women with impaired ovarian function, it seems that COCs have a positive influence on BMD. Progestin onlypills may not affect BMD, but further research is needed. Depot medroxyprogesterone acetate injection (DMPA) has a negative impact, especially in adolescents, which is duration related but evidence shows that BMD recovers after discontinuation. Levonorgestrel-releasing intrauterine system (LNG-IUS) has no impact on BMD.