Uloga omjera E2/P u etiologiji fibrocistične bolesti dojke, mastalgije i mastodinije

The aim of the study was to assess the role of the estradiol and progesterone relationship during the late luteal phase and the occurrence of fibrocystic breast disease (FBD). The concentration of estradiol/progesterone was measured in the group of women with FBD as study group (n=50) and control group of women without FBD (n=40). All women had regular ovulation cycles. Blood samples for estradiol (E2), progesterone (P) and prolactin determination were obtained in the morning at 8 am on days 21 and 24 of menstrual cycle. Significant mastalgia and mastodynia history in women with FBD was obtained with yes or no questionnaire. FBD diagnosis was confirmed with ultrasound (size and number of simple cysts). In the control group, a reduced E2/P ratio was noticed from day 21 to day 24 of the cycle (from 14.8±11.5 pg/mL to 9.1±6.1 pg/mL; p<0.05), which was not recorded in the group of women with FBD (study group). Even the slightest disturbance of the E2/P ratio may contribute to the occurrence of FBD with clinical manifestations of mastalgia and mastodynia.Namjera rada je bila ispitati ulogu odnosa estradiola i progesterona za vrijeme lutealne faze ciklusa u pojavljivanju fibrocistične bolesti dojke (FBD). Koncentracija odnosa estradiol/progesteron je bila mjerena u skupini žena s FBD (n=50) (studijska skupina) i u kontrolnoj skupini žena bez FBD (n=40) (kontrolna skupina). Sve su žene imale redovite ovulacijske cikluse. Krvni uzorci estradiola (E2), progesterona (P) i prolaktina određivali su se u 8 h ujutro 21. i 24. dana menstruacijskog cikusa. Određivanje značajnosti mastalgije i mastodinije bila je ispitana upitnikom da/ne. Dijagnoza FBD je bila potvrđena ultrazvukom dojke (veličina i broj jednostavnih cista). U kontrolnoj skupini smanjen odnos E2/P zabilježen je od 21. do 24. dana ciklusa (od 14,8±11,5 pg/mL do 9,1±6,1 pg/mL; p<0,05), za razliku od žena studijske skupine gdje ta promjena nije bila zapažena. Čak i mala promjena odnosa E2/P može doprinijeti nastanku FBD s kliničkim manifestacijama mastalgije i mastodinije

Small bowel adenocarcinoma mimicking a large adrenal tumor

Introduction. Adenocarcinoma of the small bowel is a rare gastrointestinal neoplasm usually affecting the distal duodenum and proximal jejunum. Because of their rarity and poorly defined abdominal symptoms, a correct diagnosis is often delayed. Case Outline. We present a 43-year-old woman admitted at the Clinic for Endocrinology due to a large tumor (over 7 cm) of the left adrenal gland. The tumor was detected by ultrasound and confirmed by CT scan. The patient complained of abdominal pain in the left upper quadrant, fatigue and septic fever. Normal urinary catecholamines excluded pheochromocytoma. The endocrine evaluations revealed laboratory signs of subclinical hypercorticism: midnight cortisol 235 nmol/L, post 1 mg - overnight Dexamethasone suppression test for cortisol 95.5 nmol/L and basal ACTH 4.2 pg/mL. Plasma rennin activity and aldosterone were within the normal range. Surgery was performed. Intraoperative findings showed signs of acute peritonitis and a small ulceration of the jejunum below at 70 cm on the anal side from the Treitz’s ligament. Adrenal glands were not enlarged. Patohistology and immunochemistry identified adenocarcinoma of the jejunum without infiltration of the lymphatic nodules. The extensive jejunal resection and lavage of the peritoneum were performed. Due to complications of massive peritonitis, the patient died seven days after surgery. Conclusion. Poorly defined symptoms and a low incidence make the diagnosis of small bowel carcinoma, particularly of the jejunal region, very difficult in spite of the new endoscopic techniques

Collagen type I alpha 1 gene polymorphism in premature ovarian failure

Introduction. Premature ovarian failure (POF) is characterized by amenorrhea, hypergonadotropism and hypoestrogenism in women bellow 40 years. Osteoporosis is one of the late complications of POF. Objective. To correlate collagen type I alpha1 (COLIA1) gene polymorphism with bone mineral density (BMD) in women with POF. Methods. We determined the COLIA1 genotypes SS, Ss, ss in 66 women with POF. Single nucleotide polymorphism (G to T substitution) within the Sp 1-binding site in the first intron of the COLIA1 gene was assessed by polymerase chain reaction (PCR) followed by single-stranded conformation polymorphism (SSCP) analysis. Bone mineral density (BMD) was measured at the lumbar spine region by dual X-ray absorptiometry. Statistics: Kruskal-Wallis ANOVA, Chisquare test, Spearman correlation test. Results. The relative distribution of COLIA1 genotype alleles was SS - 54.4%, Ss - 41.0% and ss - 4.5%. No significant differences were found between genotype groups in body mass index, age, duration of amenorrhea or BMD. A significant positive correlation was observed between BMI and parity. Conclusion. The COLIA1 gene is just one of many genes influencing bone characteristics. It may act as a marker for differences in bone quantity and quality, bone fragility and accelerated bone loss in older women. However, in young women with POF, COLIA1 cannot identify those at higher risk for osteoporosis.Uvod. Prevremena insuficijencija jajnika (PIJ) se odlikuje amenorejom, hipergonadotropizmom i hipoestrogenijom kod žena mlađih od 40 godina. Osteoporoza je kasna komplikacija ovog stanja. Cilja rada. Cilj istraživanja je bio da se uporede genski polimorfizam kolagena tip I alfa 1 (COLIA1) sa gustinom koštane mase kod žena sa PIJ. Metode rada. Određivan je COLIA1 genotip SS, Ss i ss kod 66 žena sa PIJ pomoću eseja za reakciju lančanog umnožavanja DNK (engl. polymerase chain reaction - PCR). Polimorfizam jednog nukleotida (zamena G u T) u okviru Sp1 vezujućeg mesta u prvom intronu gena COLIA1 određivan je primenom PCR, nakon čega se pristupilo analizi konformacionog polimorfizma. Gustina koštane mase je merena na nivou lumbalnog dela kičme pomoću apsorpciometrije. Hormonske analize za folikulostimulišući hormon, luteinizirajući hormon, estradiol, prolaktin, progesteron i testosteron urađene su primenom metoda RIA. Pri statističkoj obradi podataka korišćeni su: Kraskal-Volisov (Kruskal-Wallis) ANOVA test, χ2-test i Spirmanov (Spearman) test korelacije. Rezultati. Relativna distribucija alela COLIA1 genotipa bila je: SS 54,4%, Ss 41,0% i ss 4,5%. Nije utvrđena značajna razlika između grupa prema genotipu za gustinu koštane mase, starost ispitanica, period amenoreje ili indeks telesne mase žena. Značajna pozitivna korelacija je uočena za indeks telesne mase i paritet. Zaključak. COLIA1 je samo jedan od mnogih gena koji utiču na karakteristike kosti. Kod žena starije životne dobi on može biti marker kvaliteta, kvantiteta i osetljivosti kosti. Kod mladih žena sa PIJ COLIA1 ne može da ukaže na one žene kod kojih postoji veći rizik za nastanak osteoporoze.Projekat ministarstva br. ON 17305

Collagen type I alpha 1 gene polymorphism in premature ovarian failure

Introduction. Premature ovarian failure (POF) is characterized by amenorrhea, hypergonadotropism and hypoestrogenism in women bellow 40 years. Osteoporosis is one of the late complications of POF. Objective. To correlate collagen type I alpha1 (COLIA1) gene polymorphism with bone mineral density (BMD) in women with POF. Methods. We determined the COLIA1 genotypes SS, Ss, ss in 66 women with POF. Single nucleotide polymorphism (G to T substitution) within the Sp 1-binding site in the first intron of the COLIA1 gene was assessed by polymerase chain reaction (PCR) followed by single-stranded conformation polymorphism (SSCP) analysis. Bone mineral density (BMD) was measured at the lumbar spine region by dual X-ray absorptiometry. Statistics: Kruskal-Wallis ANOVA, Chisquare test, Spearman correlation test. Results. The relative distribution of COLIA1 genotype alleles was SS - 54.4%, Ss - 41.0% and ss - 4.5%. No significant differences were found between genotype groups in body mass index, age, duration of amenorrhea or BMD. A significant positive correlation was observed between BMI and parity. Conclusion. The COLIA1 gene is just one of many genes influencing bone characteristics. It may act as a marker for differences in bone quantity and quality, bone fragility and accelerated bone loss in older women. However, in young women with POF, COLIA1 cannot identify those at higher risk for osteoporosis.Uvod. Prevremena insuficijencija jajnika (PIJ) se odlikuje amenorejom, hipergonadotropizmom i hipoestrogenijom kod žena mlađih od 40 godina. Osteoporoza je kasna komplikacija ovog stanja. Cilja rada. Cilj istraživanja je bio da se uporede genski polimorfizam kolagena tip I alfa 1 (COLIA1) sa gustinom koštane mase kod žena sa PIJ. Metode rada. Određivan je COLIA1 genotip SS, Ss i ss kod 66 žena sa PIJ pomoću eseja za reakciju lančanog umnožavanja DNK (engl. polymerase chain reaction - PCR). Polimorfizam jednog nukleotida (zamena G u T) u okviru Sp1 vezujućeg mesta u prvom intronu gena COLIA1 određivan je primenom PCR, nakon čega se pristupilo analizi konformacionog polimorfizma. Gustina koštane mase je merena na nivou lumbalnog dela kičme pomoću apsorpciometrije. Hormonske analize za folikulostimulišući hormon, luteinizirajući hormon, estradiol, prolaktin, progesteron i testosteron urađene su primenom metoda RIA. Pri statističkoj obradi podataka korišćeni su: Kraskal-Volisov (Kruskal-Wallis) ANOVA test, χ2-test i Spirmanov (Spearman) test korelacije. Rezultati. Relativna distribucija alela COLIA1 genotipa bila je: SS 54,4%, Ss 41,0% i ss 4,5%. Nije utvrđena značajna razlika između grupa prema genotipu za gustinu koštane mase, starost ispitanica, period amenoreje ili indeks telesne mase žena. Značajna pozitivna korelacija je uočena za indeks telesne mase i paritet. Zaključak. COLIA1 je samo jedan od mnogih gena koji utiču na karakteristike kosti. Kod žena starije životne dobi on može biti marker kvaliteta, kvantiteta i osetljivosti kosti. Kod mladih žena sa PIJ COLIA1 ne može da ukaže na one žene kod kojih postoji veći rizik za nastanak osteoporoze.Projekat ministarstva br. ON 17305

Finger Length Ratios in Serbian Transsexuals

Atypical prenatal hormone exposure could be a factor in the development of transsexualism. There is evidence that the 2nd and 4th digit ratio (2D : 4D) associates negatively with prenatal testosterone and positively with estrogens. The aim was to assess the difference in 2D : 4D between female to male transsexuals (FMT) and male to female transsexuals (MFT) and controls. We examined 42 MFT, 38 FMT, and 45 control males and 48 control females. Precise measurements were made by X-rays at the ventral surface of both hands from the basal crease of the digit to the tip using vernier calliper. Control male and female patients had larger 2D : 4D of the right hand when compared to the left hand. Control male’s left hand ratio was lower than in control female’s left hand. There was no difference in 2D : 4D between MFT and control males. MFT showed similar 2D : 4D of the right hand with control women indicating possible influencing factor in embryogenesis and consequently finger length changes. FMT showed the lowest 2D : 4D of the left hand when compared to the control males and females. Results of our study go in favour of the biological aetiology of transsexualism

The great pretender: Could a pheochromocytoma manifest itself as a seizure?

Epileptic seizures are defined as the transient appearance of signs or symptoms due to excessive or synchronous neuronal activity in the cerebral cortex. Pheochromocytomas and paragangliomas (PPGL) are tumors of chromaffin cells that arise from the medulla of the adrenal gland in 80-85% of patients and from the extra-adrenal sympathetic tissue of the abdomen, pelvis and chest in 10-20% of patients. The clinical picture of PPGL is variable and ranges from the absence of symptoms to severe clinical picture, depending on the biochemical profile. They are most often manifested by paroxysmal hypertension, followed by episodes of severe headache or diaphoresis, while epileptic attacks are rare. Neurological symptoms are present in many patients with PPGL. Also, paroxysmal neurological conditions such as vasodilating headache, intracranial tumors, diencephalic-autonomic epilepsy, hypertensive encephalopathy, focal arterial disease of the brain and anxiety state have been described, which may have similar clinical manifestations with pheochromocytomas. We present a 44-year-old woman, who has been diagnosed with pheochromocytoma as possible etiological basis of epileptic seizures. Pheochromocytoma, with its low incidence and "chameleon" clinical spectrum, should be considered as a potential etiological factor of convulsions

<i>Foeniculum vulgare</i> Miller, a New Chemotype from Montenegro

Previous studies relating to prolonged and fractionated distillation procedures highlighted essential oils’ (EOs) chemical composition to be significantly dependent on the extraction duration and harvesting time. As a continuation, a hydrodistillation procedure was applied to ripe fruit material of fennel, Foeniculum vulgare Miller (Apiaceae), collected from three localities in Montenegro (Podgorica, Nikšić, and Kotor) to furnish a total of 12 EOs. Liquid and vapor phases of the samples were analyzed by Gas Chromatography/Mass Spectrometry and Headspace-Gas Chromatography/Mass Spectrometry techniques, and 18 compounds have been identified. Although both quantitative and qualitative differences between the samples were notable, the phenylpropanoids anethole (ANE) and estragole and the monoterpenoids α-terpineol (TER) and fenchone (FEN) could be singled out as the most abundant constituents. The EOs from Podgorica belong to the most common ANE-rich chemotype, while the predominance of the monoterpenoid fraction is characteristic of the samples from Nikšić and Kotor. The latter is particularly rich in TER (up to 56.5%), with significant amounts of FEN and ANE. This chemical profile could represent a new chemotype of fennel EO. Vapor phases contained mainly monoterpenoids, with increased amounts of FEN and TER, while the number of phenylpropanoids was significantly decreased

Genetska etiologija prijevremene insuficijencije jajnika

Primary premature ovarian insufficiency (PPOI) is characterized by hypergonadotropic amenorrhea and hypoestrogenism in women under 40 years of age. PPOI incidence is 1:10,000 in women aged 18-25, 1:1000 in women aged 25-30 and 1:100 in women aged 35-40. In 10%-28% of cases, PPOI causes primary and in 4%-18% secondary amenorrhea. The process is a consequence of accelerated oocyte atresia, diminished number of germinated cells, and central nervous system aging. Specific genes are responsible for the control of oocyte number undergoing the ovulation process and the time to cessation of the reproductive function. A positive family history of PPOI is found in 15% of women with PPOI, indicating the existing genetic etiology. Primary POI comprises genetic aberrations linked to chromosome X (monosomy, trisomy, translocation, deletion) or to autosomal chromosome. Secondary POI implies surgical removal of ovaries, chemotherapy and radiotherapy, and infections. Diagnostic criteria include follicle stimulating hormone level >40 IU/L and estradiol level <50 pmol/L.Primarna prijevremena insuficijencija jajnika (PPIJ) je sindrom koji je obilježen hipergonadotropnom amenorejom i hipoestrogenizmom. Incidencija PPIJ je 1:10.000 kod žena starosti 18-25 godina, 1:1000 kod žena starosti 25-30 godina i 1:100 kod žena starosti 35-40 godina. U 10%-28% slučajeva PPIJ je uzrok primarnih, a u 4%-18% sekundarnih amenoreja. Bolest nastaje kao posljedica ubrzanog procesa atrezije oocita, smanjenja broja germinativnih stanica i starenja središnjeg živčanog sustava. Specifični geni su odgovorni za kontrolu broja oocita koji prolaze proces ovulacije i vrijeme prekida reproduktivne funkcije. Pozitivna obiteljska anamneza PPIJ nađena je u oko 15% žena s PPIJ, što ukazuje na postojanje određene genetske etiologije. Primarna insufi cijencija jajnika (PIJ) dijeli se na primarnu i sekundarnu. U primarnu PIJ spadaju genetske aberacije vezane za kromosom X (monosomije, trisomije, translokacije, delecije) ili one vezane za autosomne kromosome. U sekundarnu PIJ spadaju kirurško odstranjenje jajnika, liječenje kemoterapijom i radioterapijom te infekcije. Simptomi su razdražljivost, nemir, gubitak libida, depresija, nesanica, dekoncentracija, napadaji vrućine, povišenje tjelesne težine, suhoća vagine i drugih sluznica. Kriteriji za dijagnozu su folikulostimulirajući hormon viši od 40 IJ/L i estradiol (E2) niži od 50 pmol/L kod žena mlađih od 40 godina

Effects of continuous-combined oral drospirenone- estradiol on blood pressure, body weight & lipid profile in early menopausal women

Background & objectives: Drospirenone (DRSP) is a progestin with antimineralocorticoid and anti-androgenic activity. When administered in combination with estradiol (E2), it relieves menopausal symptoms. The aim of this study was to evaluate the effects of DRSP/E2 on the reduction of cardiovascular risk factors in menopausal women with hypertension. Methods: A retrospective study was conducted at the Clinical Center of Serbia. The participants were 64 menopausal women [mean age=49.19±4.62 yr, mean body mass index (BMI)=25.08±2.94 kg/m2, mean amenorrhoeic period=2.48±2.46 yr]. The effects of DRSP 2 mg/E2 1 mg on 24 h blood pressure (BP) variability, heart rate (HR), anthropometric characteristics and hormone and lipid levels were evaluated in early menopausal women with previously untreated stage 1 hypertension. All analyses were carried out before and after six and 12 months of therapy. Results: DRSP/E2 significantly reduced daytime BP values during six and 12 months of therapy. The reductions in systolic and diastolic BPs ranged from about −4.50 to −8.50 and from −4.00 to −5.00 mmHg, respectively. There were no significant changes in nocturnal 24 h BPs. DRSP/E2 significantly reduced HR daytime and night-time during the follow up period. DRSP/E2 significantly lowered the BMI, concentrations of total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B, while high-density lipoprotein cholesterol and apolipoprotein concentration increased. Interpretation & conclusions: Continuous long-term therapy with DRSP 2 mg/E2 1 mg significantly lowered 24 h systolic and diastolic BPs and reduced the risk of cardiovascular disease in early menopausal women with stage 1 hypertension. Timely initiated menopausal hormone therapy can have beneficial effects on BP and can reduce the incidence of cardiovascular disease in menopausal women

Alzheimer’s Disease and Premature Ovarian Insufficiency

Estradiol promotes neuronal growth, transmission, survival, myelinization, plasticity, synaptogenesis, and dendritic branching and it improves cognitive function. Alzheimer’s disease (AD) is characterized by amyloid plaques, neurofibrillary tangles, and the loss of neuronal connection in the brain. Genomic analysis has concluded that hypoestrogenism influences the APOE gene and increases the risk of AD. Premature ovarian insufficiency (POI) is defined as oligo/amenorrhea in women below 40 years of age, low estradiol, and high-gonadotropin levels. Early symptoms and signs of POI must be detected in time in order to prevent subsequent complications, such as Alzheimer’s disease. Meta-analysis has shown favorable effects of estrogen in preventing Alzheimer’s. We measured some of the typical markers of AD in women with POI such as interleukin 6 (IL-6), interleukin 8 (IL-8), tissue necrosis factor α (TNFα), TAU1, TREM2, and amyloid precursor proteins (APP). While FSH, LH, and IL-8 were significantly higher in POI group, compared to controls, testosterone and DHEAS were lower. A significant decrease in IL-6 was found in the POI group during a 6-month therapy, as well as an increase in amyloid precursor proteins. CONCLUSION: Neurological complications of POI, such as declining short-term memory, cognitive function, and dementia, have to be promptly stopped by initiating estro-progestogen therapy in POI. A long-term continuation of the therapy would be strongly advised