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Introduction: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive diseases caused by a deficiency of enzymes responsible for the steroidogenesis. There are three forms of CAH due to 21-hydroxylase deficiency: the classic form with salt loss, the classic virilizing and the non-classic form. The aim of the paper was to analyze the changes in the diagnosis and treatment of children with CAH during previous 15 years. Material and methods: This retrospective cohort study includes patients who were diagnosed with CAH due to 21-hydroxylase deficiency in the period from 2007 to 2021 in endocrinology department of the Institute for Mother and Child Health Care Institute of Serbia "Dr Vukan Cupic". Respondents were divided into two groups - a group whose diagnosis was made in the period between 2007 and 2014 and another group of those whose diagnosis was made in the period between 2015 and 2021. Statistical analysis using Hi-square and Mann Whitney U test was conducted using the software IBM SPSS ver. 22, and p values

Introduction/aim: Disorders of sex development (DSD) comprise a heterogeneous group of congenital conditions with a difference between chromosomal, gonadal sex and the appearance of the external genitalia. The frequency of DSD is 1: 4,500-5,500 newborns per year. Congenital adrenal hyperplasia (CAH) due to the deficiency of the 21-hydroxylase enzyme is one of the most common and best-known causes of DSD. Other forms of CAH, as well as other causes of DSD, occur with significantly lower individual frequencies and are thus more challenging to diagnose and treat. The aim of the study was to analyse the etiology and clinical characteristics of DSD, as well as changes in the diagnostic and therapeutic approach to DSD in the tertiary center during the previous 13 years. Methods: The study was conducted in the form of a retrospective cohort study which included all patients investigated for DSD at the Department of Endocrinology of Mother and Child Health Care Institute of Serbia "Dr Vukan Cupic" during the period from December 2007 until November 2020. Children with DSD caused by CAH due to 21-hydroxylase deficiency were not included in this study. Results: The study included a total of 31 children with DSD: 24 children (77%) had 46XY DSD, 3 (10%) had 46XX DSD, and 4 children (13%) had chromosomal DSD. A definitive diagnosis of specific etiology has been made in 25 children (81%), and the most common etiology of DSD was gonadal dysgenesis (55%), followed by the androgen insensitivity syndrome (10%) and atypical forms of CAH (7%). During the period 2 (2016-2020) more children with DSD (n = 18) were examined compared to the period 1 (2007-2015) and the specific etiological diagnosis was established in a larger number of children with DSD (89%) compared to the period 1 (69%). Also, during period 2 (2016-2020) genital surgery was performed in a significantly lesser number of children (11%) and at a later age (average age 6.8 years) than in period 1 (64%, average age 4.8 years; p

Introduction. Investigation of sexual and reproductive behaviour of youth in Serbia has not been performed by Internet, although it is their popular information and communication channel. Objective. Analysis of the Internet acceptability among adolescent females as a research method for sexual and reproductive behaviour, identification of the common girl from Serbia, which is informed via the Internet, as well as an overview of the most important problems in the field of sexual and reproductive health of our adolescents. Methods. The possibility of using the Internet is perceived on the basis of the number of girls aged 19­20 years who responded to certain questions asked on the website of the Association of Reproductive Health of Serbia, and reliability of the findings by monitoring the consistency of the obtained responses. Girl’s profile is defined according to most commonly selected answer to a particular issue, and the most important problems by selecting answers to some questions chosen by a significant proportion of patients. Results. Internet has proven to be the accepted research tool among young people, according to a large number of adolescent females who responded to the given questionnaire. The common girl lives in the city (78%), with parents (53%), in the functional family (78%) and belongs to a higher economic stratum (47%). She declares having many friends (44%), being a student, and financially completely relying on parents (67%). She had first sexual intercourse at the age of 17 (20%) and sexual experience with one partner (46%). Her main motive for sexual activity is being in love (64%), and is satisfied with her sexual life (64%). She prefers condom as a contraceptive method, has not been pregnant (90%), and has not been diagnosed with STI (85%). At the same time, serious problems, which may affect sexual and reproductive health, have been identified in a significant proportion of respondents. Conclusion. Internet has a great potential for defining the model of sexual and reproductive behavior of youth, and offers the possibility of alleviating these problems by a variety of activities, including sending motivational messages via Internet. [Projekat Ministarstva nauke Republike Srbije, br. 47006]

The problem of a large number of abortions in our country was first pointed out as far back as 1935 at the 17th Congress of Yugoslav Physicians. The abortion problem in Serbia is still present today, even though modern science has provided new methods and means which are a logical solution to the dilemma on birth control methods from the health and social aspect. Namely, total abortion rate in Serbia was estimated at 2.76 in the year 2007. It is very high; double the number of the total fertility rate and among the highest in Europe and the world. The term abortion culture was first used, as far as we know, by Henry David in the introduction of the book From Abortion to Contraception - A Resource to Public Policies and Reproductive Behavior in Central and Eastern Europe from 1917 to the Present in 1999, without specifically determining it. The aim of this paper is to identify the most important factors of the deterministic basis of endemic induced abortions in Serbia together with indirectly estimating their connection with the existence, namely nonexistence, of the abortion culture in our country. In that sense, potential factors of abortion incidence in Serbia which emerge from the social system and those connected to the individual level have been considered. In other words, a series of laws and other legal and political documents have been analyzed which are significant for perceiving the abortion matter, as well as institutional frameworks for family planning, health services, educating the youth regarding reproductive health, including findings of numerous researches carried out among women of various age and doctors from 1990 till present day in Serbia. The following most significant factors for the long duration of the abortion problem have been singled out: insufficient knowledge of modern contraception, a belief that modern contraceptive methods are harmful to health and a number of psychological barriers as well as those arising from relationships with partners. Gynecological attitudes about modern contraception and behavior do not differ significantly from the rest of the population. Additionally, there are few organized efforts to promote sex education, as well as limitations in the family planning programme. Distinguished macro and micro factors of traditional birth control in Serbia confirm the existence of the abortion culture. The nature of these factors though, indicate to the presence of the abortion culture in our country on the political, educational, health and individual level. The abortion culture obstructs the adoption of a modern concept of family planning and points out to the persistence of the abortion problem in our country in the years to come.

Traditional inefficient contraception, incorporated to a large extent in the system of values, has become a natural part of sexual relations in Serbia and represents a rational preventive choice from the individual standpoint. However, when pregnancy is unwanted or cannot be accepted out of any reasons abortion is used as a resort. For this reason there is a long history of a large number of abortions in Serbia. Research findings in our country identify the following, as the most important factors for not accepting modern values in this sphere: traditional contraception and abortion have a firm social confirmation; there is a trans-generational transfer of psychological resistance towards the use of combined oral contraception pills and intrauterine devices; sexual education has never become a natural way of growing up in the family, nor is a constituent part of school programs and that distinct obstacles of various nature exist regarding contraception availability. A developed network of various types of family planning counseling is an important determinant of the accessibility of contraceptive means and methods. There are, however, numerous conditions which have to be fulfilled in order for the contraception counseling services to function properly. Among them, motivated personnel who acquired general and specific knowledge for work in this field are an especially important prerequisite. This theoretical assumption opens the question -whether gynecologists represent an important factor of slow transition of birth control in Serbia? We searched for the answer in the research analyses obtained through two in-depth surveys which either had to do with this theme or tried to determine the knowledge, attitude and practice of gynecologists. The first research regarding the determination of the causes for a large number of abortions in our country, was directed towards women who decided on abortion. Gynecologists were the target group in the second research which was KAP type. The results of both researches clearly indicate that gynecologists generally observed, contribute to maintaining the abortion culture and slow transition of birth control from the use of traditional contraception to reliance on modern contraception means and methods in Serbia. Namely, a significant number of gynecologists in our country are at variance with the principals of modern family planning. Their knowledge, attitudes and practice relevant for individual contraceptive choices are insufficient, conservative and inadequate. Thus, there is a necessity for special education of doctors especially gynecologists, at all levels from the basic studies, through specialists ones, to special target courses, seminars, symposiums and conferences. Knowledge acquisition, as the basic element of consciousness can affect formation of standpoints, motivation, promote responsibility and create the requirement for promoting a different system of values and philosophy of living in the sphere of reproductive health.

Background Benign ovarian neoplasms originating from epithelial tissue are common tumors in adult women. However, they are rarely seen in the pediatric population, especially in the first decade of life. Case We report a case of a 6-year-old, premenarchal girl, previously healthy, with frequent micturition lasting 3 days prior to the first examination, without discomfort or pain. Laboratory analyses of blood and urine showed no abnormalities. Repeated ultrasonographic examinations revealed bilateral, cystic, rapidly growing ovarian masses. Cysts were surgically removed, with preservation of normal ovarian tissue, and histopathologic findings showed a serous cystadenoma of both ovaries.

The question if voluntary sterilization is accepted in Serbia has been imposed for research, regardless of the fact that this birth control method is neither accessible nor promoted.The attitudes of women who decided to terminate pregnancy and of gynecologists from various parts of Serbia were explored by specially designed anonymous questionnaires.More than half of the surveyed women believe that voluntary sterilization should be available in Serbia and almost half would subject themselves to this surgical procedure. Younger women, respondents with secondary education, those who have the desired number of children, as well as those who have a good relationship with partner, who have experienced a large number of abortions, namely those who wish to use contraception, are more open to voluntary sterilization. The majority of gynecologists think that voluntary sterilization should become available in Serbia. Medical and eugenic reasons are, according to their opinion, the main indications for sterilization. The gynecologists lack current knowledge about this contraceptive method, and would not accept to use voluntary sterilization themselves.There is a need for voluntary sterilization as a contraceptive choice in Serbia. Relevant knowledge of women as well as gynecologists about voluntary sterilization should be improved.

Introduction. Precocious puberty in girls is generally defined as appearance of secondary sexual characteristics before eight years of age. Menarche before the ninth birthday may serve as an additional criterion. Precocious puberty is divided in central precocious puberty and pseudoprecocious puberty. Central precocious puberty (GnRH dependent) occurs because of premature activation of hypothalamic-pituitarygonadal axis and activity of gonadotrophins. Pseudoprecocious puberty (GnRH independent) is caused by activity of sexual steroids that are not the result of gonadotrophin activity. Objective. Objective of our study was to examine the etiology, clinical and laboratory manifestations of isosexual pseudoprecocious puberty in girls. Method. In the period between 1995 and 2004, clinical and laboratory sings of 34 girls with precocious puberty were studied at the Endocrine Department of the Institute of Mother and Child Health Care of Serbia. Initial evaluations included height measurement, staging of puberty, bone age assessment and pelvic ultrasound. Important diagnostic sonographic parameters of precocious puberty were the volumes of ovaries and uterus as well as ovarian structure. The initial hormonal evaluation included measuring of plasma oestradiol, luteinizing hormone (LH) and follicle stimulating hormone (FSH). The luteinizing hormone releasing hormone (LHRH) stimulation test was used to evaluate LH and FSH responsiveness (60 ?g/m2 LHRH- Relefact LHRH?, Ferring). Blood samples were collected at 0, 20 and 60 minutes. Basal and GnRH stimulated LH and FSH were determined by immunoradiometric assay. Estradiol concentration was measured using the fluoroimmunometric assay. Results. Thirty-four girls aged 6 months to 9 years (mean age 4.5 years) with precocious puberty were studied during the period of 9 years. Eleven girls presented with breast development, six with vaginal bleeding and seventeen with signs of puberty. On the basis of clinical signs, bone age, estradiol levels and LHRH test, premature the larche was diagnosed in eleven patients (32.4%), premature menarche in six (17.6%) and central precocious puberty in ten girls (29.4%). Seven girls (20.6%) presented with pseudoprecocious puberty. Pelvic ultrasound examination revealed unilateral ovarian cysts in six patients and granulosa cell tumor in one. Elevated estrogen serum levels and failure of gonadotropin responses after gonadotropin releasing hormone were the classical findings in patients with isosexual pseudoprecocious puberty during the acute period of disease. In four patients, the cyst decreased spontaneously after several months, while in two patients, the cyst was removed by laparotomy. Surgical treatment was performed in a patient with granulosa cell tumor. Conclusion. Our work demonstrates that autonomous functional ovarian follicle cyst is the most often cause of isosexual pseudoprecocious puberty. Short period of observation is suggested because the cyst can resolve spontaneously. On the other hand, juvenile granulosa cell tumor, as highly malignant tumor, should be removed as soon as diagnosis is established.

Increase in adolescent sexual activity is a phenomenon noticed in modern societies, as well as in Serbia. The sexual activity reveals new health related problems, in relation to the unpremeditated pregnancies and sexually transmitted diseases. Reproductive health is vulnerable especially in case of persons having first sexual experiences being adolescent, what could be explained by the physical immaturity and psychosocial infirmity to be responsible in sexual behaviour. The study of 300 sexually active adolescent women aged 19, attending The Youth Advisory Center of The Mother and Child Health Care Institute of Serbia was conducted between 1995 - 1997. The aim of this study was to evaluate how much the reproductive health in this population was endangered, by analyzing their sexual behavior, their attitudes in the spheres of sexuality and reproduction, as well as some variables of social microenvironments that might be relevant to adolescent sexual behavior. Questionnaire included investigation of youth opinion about some acceptable social measures in this field. According to the results of this study the adolescents reproductive health is seriously endangered. Interwieved adolescent females most frequently used traditional birth control methods, like coitus interruptus (54,3%), and often didn't think about the risk of acquiring sexually transmitted disesase (with new sexual partner the regular condom use was reported only in case of 55,6% girls). Adolescent girls had also poor health behaviors so that 31,0% of interviewed adolescent females visited gynecologist for the first time not earlier than one to three years after their first sexual experience. That resulted in large number of unplanned pregnancies (16,0% of interwieved girls had one or more induced abortions) and, possibly, a high prevalence of sexually transmitted infections. The model of sexual behavior, that was accepted by adolescent females was partly due to the lack of adolescents knowledge about sexuallity, contraception and sexually transmitted diseases. Improper were the main sources of relevant knowledge (peers, parents, mass media), therefore, youth had many misconceptions in this sphere (about the harmfulness of modern contraception, reliability of coitus interruptus method, lack of risk for sexually transmitted diseases transmission). The social adolescent sexual and reproductive health programme doesn't exist in Serbia. Parents of adolescent females were passive, and school and health care workers are not engaged in these matters enough. The possibility for social intervention programme exists, because young people were willing to improve their knowledge about sexuality and reproduction (83,3%) mostly by sex education in schools (51,0%) and through mass media (33,3%). The most appreciated sources of relevant knowledge would be physicians (67,0%), from whom they expect to have time and patience for them and their problems (91,3%).

Dowrloaded from jfprhc,bmj.corn on November 7,2013 - Punished by grouytnni com =.::'«l SVVIU E ‘ME WT For nurnbened affiliations see end of article. Correspondence to Professor Dr Johan res Bitzer. Chief Physician and Chairman Department of Obnettics and Gynaecology. University Hospital Basel. Basel. Switzerland; JohartnesBitzer@usb.cl‘. Received IS March 2013 Accepted 18 March 2013 To cite: Bitzer J Amy J-J. Beerttmizer R. et al. Joumai of Fanfly Planning and Reproductive Health C are Published Online First lnlease include Day Month Year] doi: 10. l l36lifptl1(-20l3- 100624 Statement on combined hormonal contraceptives containing third- or fourth-generation progestogens or cyproterone acetate, and the associated risk of thromboembolism Johannes Bitzer Cosignatories Jean-Jacques Amy,‘ Rob Beerthuizen,2 Martin Birkhauser,3 Teresa Bombas,“ Mitchell Creinin,5 Philip D Darney,5 Lisa Ferreira Vicente,’ Kristina Gemzell-Danielsson,° Bruno lmthurn,9 Jeffrey T Jensen,” Andrew M Kaunitz,“ Ali Kubba,” Medlard M Lech,” Diana Mansour,” Gabriele Merki,” Thomas Rabe,‘6 Katarina Sedlecki,” David Serfaty,‘8Jact1ues Seydoux,” Lee P Shu|man,2° Regine Sitruk-Ware, ‘ Sven O Skouby,” Anne Szarewski, James Trussell,” Carolyn Westhoffzs A NEW PILL SCARE? HOW DID IT COME ABOUT AND HOW SHOULD WE TACKLE IT? The cotttroversy around the combined hormonal contraceptives ((IH(,'s) of the so-called third (containing gestodene or desogestrel) and fourth generation (cott- raining drospirenone. DRSP) lt-as reached .1 highly emotional political dimension in which all those who “are prol'essionall_v responsible for women's health are involved: the national health authorities, the pltarrnaceutical companies, the pro- fessional orgartis-ations, the prescrihers. the media and the public (i.e. the current or potential users of CH(Is). The — initially scientific — controversy has now led to a ptthlic health dispute that culminated in the decision of the Frenelt '.1tltht)ritlc's to withdraw the com hination containing etltinylestradiol (EE) and cyproterone acetate (CPA) from the market. The potential impact of this measure, namely the loss of confidence in .1/I (Ill(.'s. could be quite serious. WHAT TRIGGERED THIS CRISIS? Several re;.',is‘tr_v~hasei.l studies published in the Britr'.~‘l2 .\ledic.tl Irirrrmtl. partictilarlv 23 the one based on the Danish Registry. indicated that there is an increased risk of venous thrombiternholism (VTE) asso- ciated with the intake of third- and liounh-generation combined oral contra- ceptives ((ZO('.s) compared to prepara- tions containing the progestogen le\'onorges‘trel (I-.\l(§).q5 The relative risk (RR) was around 2. and the absolute attributable risk was estimated to be (dependent on the background preva- lence rate) between .2 to 8 per ll) llllll users per year.q A very recent systentatic review and meta-anal_vsis of the possible link between treatment with CHCs and VTF. con- cluded that. in this regard. (I) (3H(Zs cort- taining I.N(} or norgestimate were the safest. (.1) those containing desogestrel. DRSI’ or (IPA were associated with a sig- ttillC.‘tI1tl_\' ltiglter risk than (IH(Is contain- ing LNG, and (3) the aup,ntented risk of VTE found for pills containing gestodene compared to (l(.)(Ls with L\'(; appeared to be smaller than in earlier s'tttcllcs.7 These resultsq contrast with those of published prospective cohort studies. sponsored by It’-a_ver He-altlt(.are. at the request of the European Medicitte Bitzer J et J Journal offamily Planting and Reolodzcme Health (.19 20‘~3;0:'-at doizt 0.’ ’-36Ii?prh: 2073 ‘0062-1 1

Objective: To investigate the importance of morphological scoring systems in differentiation of ovarian tumors in childhood. Methods: Morphological assessment using DePriest's index was performed for all patients with histopathological confirmation of ovarian tumor, with evaluation of tumor markers, from January 1997. Results: Fifty-three girls (age range 13 months to 19 years) were surgically treated for 59 ovarian tumors, including six bilateral. All lesions with cystic appearance on ultrasonography were benign, 23 of 35 semisolid, and four of ten solid tumors were also benign. Stage of malignant disease was as follows: stage I, ten; stage II, two; stage III, six. Sensitivity, positive predictive value and accuracy by DePriest's and Ueland's indexes for benign tumors (score

Introduction. Voluntary sterilization is a very effective and safe birth control method. Is it, however, accepted as a birth control method in Serbia? This is certainly a question that should be explored, regardless of the fact that voluntary sterilization is neither accessible nor promoted. Material and methods. The target group included women who decided to terminate their pregnancy, and gynecologists from various parts of Serbia. Results and disussion. The survey results indicate that more than half of women believe that voluntary sterilization should be available in Serbia. Also, a large number of surveyed women, almost half of them, would undergo voluntary sterilization. Younger women, respondents with secondary education, those who gave birth to a desired number of children, as well as those who have a good relationship with their partners, those who have experienced a great number of induced abortions, namely those who wish to use contraception in the future, are more open to voluntary sterilization. The majority of gynecologists also think that voluntary sterilization should become available in Serbia. Most of them consider therapeutic and eugenic reasons as appropriate for surgical sterilization. However, gynecologists lack current knowledge about this contraceptive method, and would not accept to use voluntary sterilization themselves. Conclusion. The reasons for individual nonacceptance indicate that many of the registered ambivalent or negative opinions can be changed by spreading knowledge on voluntary sterilization. Moreover, the knowledge of gynecologists about voluntary sterilization should be improved as well.

2007 and between 2007 and 2009. Overall, 36% of abnormal Paps resulted in colposcopy, 39% were followed with repeat Pap only, 18% were pending repeat Pap, and 7% were lost to follow up. However, significantly more girls had colposcopy ( biopsy) for abnormal cytology prior to 2007 than after (45% vs. 19%; P 5.005). Vaccination records revealed that 32% of girls had no HPV vaccine, 18% had one dose, 20% had two doses, and 30% had all three doses. Girls with at least one HPV vaccine had a lower prevalence of Pap abnormalities than girls who had none (P5.060), even when vaccination began after first Pap. In a sub-analysis, we compared girls with no HPV vaccines (n569) to girls with at least one HPV vaccine prior to first Pap (n542). Significantly more girls (42%) with no vaccine had at least one abnormal Pap compared to 14% of girls with at least one HPV vaccine (P5.002). The OR of having at least one abnormal Pap for the vaccinated group was 0.254 (CI5 0.0930.698; P50.008). Conclusions: In this population, the overall prevalence of cervical dysplasia was significant, with up to 1/3 of participants having one or more abnormal Pap smears. While the manner of follow-up intervention became significantly more conservative over the years we observed, this did not appear to affect the prevalence of abnormalities in those years. Importantly, those with at least one HPV vaccine prior to first Pap were less likely to present abnormal Pap results than those with no vaccine, suggesting that HPV vaccination may reduce the risk of developing cervical dysplasia.