Herlyn-Werner-Wunderlich syndrome in a adolescent girl

Herlyn-WernerWunderlich syndrome (HWWS) is a rare congenital genitourinary anomaly with uterine anomalies, unilateral cervicovaginal obstruction, and ipsilateral renal anomalies resulting from the embryological arrest of Müllerian and mesonephric ducts. The onset of nonspecific symptoms occurs after menarche. Having two normal uteri and obstructed cervix or hemivagina, the patient will have regular menses through the non-obstructed vaginal side, coinciding with cyclic pelvic pain from the encumbered blood in the obstructed side. The diagnosis is often delayed until acute complications develop

Sex Hormone Binding Globulin (SHBG) as a Marker of Clinical Disorders

Sex hormone binding globulin (SHBG) is an important protein, not only for transporting sex steroids which is its primary role, but with the discovery of a specific receptor that binds SHBG, a novel approach regarding classic ‘free-hormone hypothesis’ should be implemented. Research in SHBG gene and it expression has been done, as well as cellular signaling that controls it. It provides significant knowledge of the impact of certain well –defined cellular level signaling pathways and how they affect the level of SHBG production. Moreover, new insights have proven that SHBG isn’t just a peripherally synthesized protein. Its origin has been proven to exist in the brain, namely in the hypothalamus and the pituitary, where it is spatially closely related to oxytocin-producing neurons. The main peripheral organ that produces SHBG is the liver. Since the liver is the central metabolic organ, certain metabolic diseases will result in changed SHBG serum levels. On the other hand, endocrine disorders that affect tissues involved in sex hormone regulation will also have an impact on SHBG levels. Thusly, SHBG stands as one of the mediators between various endocrine tissues and definitely contributes with its own pathophysiological role in diseases such as: obesity, metabolic syndrome, polycystic ovary syndrome, osteoporosis, breast and prostate cancer. Its value expands to the area of clinical medicine as a marker of certain pathological states. Some studies already established its reliability and the growing trend to implement it as a useful clinical marker is present. It still remains largely understudied, from physiological and clinical aspect, but recent findings give notions that SHBG plays an important role in health and disease and could be a useful assessment marker

Combined ovulation triggering with GnRH agonist and hCG in IVF patients

The aim of the review is to analyse the combination of a gonadotrophin releasing hormone (GnRH) agonist with a human chorionic gonadotrophin (hCG) trigger, for final oocyte maturation in in vitro fertilisation (IVF) cycles. The concept being a ''dual trigger'' combines a single dose of the GnRH agonist with a reduced or standard dosage of hCG at the time of triggering. The use of a GnRH agonist with a reduced dose of hCG in high responders demonstrated luteal phase support with improved pregnancy rates, similar to those after conventional hCG and a low risk of ovarian hyperstimulation syndrome (OHSS). The administration of a GnRH agonist and a standard hCG in normal responders, demonstrated significantly improved live-birth rates and a higher number of embryos of excellent quality, or cryopreserved embryos. The concept of the ''double trigger" represents a combination of a GnRH agonist and a standard hCG, when used 40 and 34 h prior to ovum pick-up, respectively. The use of the ''double trigger" has been successfully offered in the treatment of empty follicle syndrome and in patients with a history of immature oocytes retrieved or with low/poor oocytes yield. Further prospective studies are required to confirm the aforementioned observations prior to clinical implementation

Ulipristal Acetate in Emergency Contraception

Despite the widespread availability of highly effective methods of contraception, unintended pregnancy is common. Unplanned pregnancies have been linked to a range of health, social and economic consequences. Emergency contraception reduces risk of pregnancy after unprotected intercourse, and represents an opportunity to decrease number of unplanned pregnancies and abortions. Emergency contraception pills (ECP) prevent pregnancy by delaying or inhibiting ovulation, without interfering with post fertilization events. If pregnancy has already occurred, ECPs will not be effective, therefore ECPs are not abortificants. Ulipristal acetate (17α-acetoxy-11β-(4N-N,N-dymethilaminophenyl)-19-norpregna-4,9-diene-3,20-dione) is the first drug that was specifically developed and licensed for use as an emergency contraceptive. It is an orally active, synthetic, selective progesterone modulator that acts by binding with high affinity to the human progesterone receptor where it has both antagonist and partial agonist effects. It is a new molecular entity and the first compound in a new pharmacological class defined by the pristal stem. Up on the superior clinical efficacy evidence, UPA has been quickly recognized as the most effective emergency contraceptive pill, and recently recommended as the first prescription choice for all women regardless of the age and timing after intercourse. This article provides literature review of UPA and its role in emergency contraception

Genetic Polymorphisms of INS, INSR and IRS-1 Genes Are Not Associated with Polycystic Ovary Syndrome in Croatian Women

Obesity and insulin resistance is a common finding in patients with polycystic ovary syndrome (PCOS). Significant number of PCOS women experience insulin resistance that is irrespective of the degree of obesity suggesting possible genetic basis. Therefore, several polymorphisms of the genes encoding for the insulin (INS), insulin receptor (INSR) or insulin receptor substrates (IRS) involved in postreceptor signaling have been explored for their association with abnormal sensitivity to insulin in PCOS. The aim of the present study was to determine whether selected polymorphisms of INS, INSR and IRS-1 are associated with the development of PCOS as well as with increased insulin resistance in Croatian women with PCOS. The study enrolled 150 women with PCOS and 175 control women. The diagnosis of PCOS was based on Rotterdam consensus criteria. Each subject underwent an evaluation of body mass index (BMI), hirsutism, acne and menstrual cycle abnormalities as well as follicular stimulating hormone (FSH), luteinizing hormone (LH), total and free testosterone, androstendione, dehydroepiandrosterone sulphate (DHEAS), sex hormone binding globulin (SHBG), fasting glucose and fasting insulin. Insulin resistance (IR) was quantified using the homeostatic model assessment of IR (HOMA-IR). Molecular analyses for the genetic polymorphisms were preformed. There was a significant difference in clinical and biochemical characteristics of the studied groups except for BMI and fasting glucose levels. No significant differences were observed in the genotype and allele distribution of the VNTR INS, C/T INSR, Gly792Arg IRS-1 polymorphisms between cases and controls. Moreover, no association was found between VNTR INS, C/T INSR and Gly792Arg IRS-1 polymorphism and parameters of insulin resistance in PCOS patients. In conclusion, our data does not support an association between VNTR INS, C/T INSR and Gly792Arg IRS-1 polymorphism and susceptibility to PCOS or insulin resistance in Croatian women with PCOS

Clinical, Hormonal and Metabolic Characteristics of Polycystic Ovary Syndrome among Obese and Nonobese Women in the Croatian Population

Obesity has a deteriorating impact on women with PCOS, although prevalence and the impact of specific traits of PCOS remain inconstant in different populations. Therefore, the aim of this study was to explore the differences in clinical, hormonal and metabolic features between obese and nonobese Croatian women diagnosed as having PCOS according to Rotterdam consensus criteria. The study included 74 obese and 208 nonobese women with PCOS. Clinical, biochemical and metabolic variables were compared among those PCOS subgroups. Obese subjects with PCOS had a higher risk of developing oligo-amenorrhea (OR 3.7; 95% CI, 1.1–12.5) and lower risk for developing hirsutism and acne (OR 0.2; 95% CI, 0.1–0.3 and OR 0.8; 95% CI 0.5–1.4, respectively). Obese PCOS subjects also had a higher risk of developing hyperandrogenemia (OR 2.5; CI 95% 0.9–6.7), insulin resistance (OR 4.5; CI 95%, 2.6–7.9), hypercholesterolemia (OR 5.0, CI 95% 2.5–10.2), hypertriglyceridemia (OR 5.2; 95% CI, 2.9–9.2) as well as elevated serum CRP levels (OR 4.1; 95% CI 1.4–12.2) compared to nonobese PCOS women. In conclusion, nonobese Croatian women with PCOS are more inclined to cosmetic problems associated with PCOS then metabolic ones. This is the first study to report the impact of obesity on acne and irregular menses as a study outcome. Obesity deteriorates menstrual regularity, insulin sensitivity and lipid profile in Croatian women with PCOS; therefore one of the fundamental treatment strategies of PCOS should be obesity prevention

Emergency Contraception: Can We Benefit from Lessons Learned?

The aim of the paper was to evaluate current emergency contraception (EC) methods and policies in order to implement lessons learned and maximize potential population impact while introducing dedicated EC pills in Croatia. Literature search for potential reasons for EC failing to show positive population impact and detecting actionable points to be implemented in national guidelines. Six potential reasons for ECs failure to show population impact were evaluated and four actionable points were detected: low use of EC compared to the numbers of risk events, low awarenes on EC in general populaton, differences in efficacy of EC methods and EC vailability. In order to ensure EC’s population impact in Croatia it is of a critical relevance to establish continuous education programs for population of women at risk. When recommending an EC method, superior efficacy must be a key decison-making criteria therefore cooper IUD and ulipristal acetate should be our primary options. Counseling is a critical step to ensure maximal efficacy of the EC method, but also to encourage future use of regular contraceptives. Finally, national ECP dispension protocol is needed to close the loop from effective women screening, prompt yet appropriate ECP administration/dispensing towards structured follow up after EC pills intake

HORMONE THERAPY IN FEMALES AND GENITAL CARCINOMA

Tamoksifen i ostali selektivni regulatori estrogenskih receptora nova su terapijska sredstva koja imaju visoki afinitet za estrogenske receptore. U određenim tkivima imaju učinak sličan estrogenima, a u drugima se ponašaju kao antagonisti estrogenske akcije. U ovom pregledu prikazana je njihova primjena i rezultati u liječenju karcinoma dojke i endometrija te je dan osvrt na njihov potencijalni učinak kod karcinoma vrata maternice i jajnika. Prema rezultatima velikog broja istraživanja tamoksifen se pokazao učinkovitim u liječenju karcinoma dojke u premenopauzalnih i u postmenopauzalnih žena. Izneseni su i rizici ove terapije poput razvoja sekundarnog karcinoma endometrija. Također je obrađena primjena gestagena u liječenju karcinoma endometrija. Ovaj rad daje i pregled utjecaja hormonske nadomjesne terapije na pojavnost raka dojke i endometrija te sigurnost njegove primjene u bolesnica liječenih zbog karcinoma dojke, endometrija, jajnika i vrata maternice.Tamoxifen and other selective estrogen receptor modulators are new medications characterised by high estrogen receptor affinity. In certain tissues they express estrogen-like activity and in the others they act as estrogen antagonists. This review discussess their use in breast and endometrial carcinoma as well as their treatment results. It also reviews their potential effects on ovarial and cervical carcinoma. According to numerous clinical trials tamoxifen has proved effective in breast cancer treatment of premenopausal and postmenopausal women. The risks of this therapy, such as development of secondary endometrial carcinoma, have also been presented. The use of gestagenes in endometrial carcinoma treatment has been discussed too. This paper reviews the influence of hormone replacement therapy on the development of breast and endometrial carcinoma as well as the safety of its application in patients diseased of breast, endometrial, ovarian or cervical carcinoma

Sex hormone binding globulin (SHBG) as a marker of clinical disorders [Globulin koji veže spolne hormone (SHGB) kao marker u kliničkim poremećajima]

Sex hormone binding globulin (SHBG) is an important protein, not only for transporting sex steroids which is its primary role, but with the discovery of a specific receptor that binds SHBG, a novel approach regarding classic ‘free-hormone hypothesis’ should be implemented. Research in SHBG gene and it expression has been done, as well as cellular signaling that controls it. It provides significant knowledge of the impact of certain well –defined cellular level signaling pathways and how they affect the level of SHBG production. Moreover, new insights have proven that SHBG isn’t just a peripherally synthesized protein. Its origin has been proven to exist in the brain, namely in the hypothalamus and the pituitary, where it is spatially closely related to oxytocin-producing neurons. The main peripheral organ that produces SHBG is the liver. Since the liver is the central metabolic organ, certain metabolic diseases will result in changed SHBG serum levels. On the other hand, endocrine disorders that affect tissues involved in sex hormone regulation will also have an impact on SHBG levels. Thusly, SHBG stands as one of the mediators between various endocrine tissues and definitely contributes with its own pathophysiological role in diseases such as: obesity, metabolic syndrome, polycystic ovary syndrome, osteoporosis, breast and prostate cancer. Its value expands to the area of clinical medicine as a marker of certain pathological states. Some studies already established its reliability and the growing trend to implement it as a useful clinical marker is present. It still remains largely understudied, from physiological and clinical aspect, but recent findings give notions that SHBG plays an important role in health and disease and could be a useful assessment marker

HORMONE REPLACEMENT THERAPY AND VENOUS THROMBOEMBOLISM

Venska tromboembolija (VTE) najvažniji je neželjeni učinak hormonskoga nadomjesnog liječenja (HNL). Biološke i epidemiološke studije pokazale su da oralna primjena estrogena nosi povišen rizik od nastanka VTE-a u odnosu na transdermalnu primjenu. Dodatak progestagena još povisuje rizik od nastanka VTE-a. Različite farmakološke klase progestagena drugačije pridonose riziku od nastanka VTE-a. Opservacijske su studije pokazale da je primjena mikroniziranog progesterona i didrogesterona sigurnija glede rizika od VTE-a u odnosu na druge progestine. Ove je rezultate nužno provjeriti randomiziranim studijama. Osobna ili obiteljska anamneza opterećena VTE-om, postojanje nasljedne trombofilije i/ili multiplih rizičnih čimbenika za nastanak VTE-a kontraindikacije su za uporabu HNL-a. U takvih se osoba može razmatrati primjena transdermalnog estrogena nakon pomne individualne procjene koristi i rizika. Transdermalno primijenjeni estrogeni također bi trebali biti prvi izbor u žena s prekomjernom tjelesnom masom, odnosno pretilosti koje trebaju primjenu HNL-a.Venous thromboembolism (VTE) is the most important side effect of using hormone replacement therapy (HRT). Biological and epidemiological studies have shown that oral administration of estrogen is associated with an increased risk of VTE compared to transdermal route of administration. Addition of progestogen to estrogen further increases the risk of VTE. Different pharmacological classes of progestogens differently contribute to the risk of VTE. Observational studies observed that the application of micronized progesterone and didrogesteron are safer regarding the risk of VTE compared to other progestins. These results should be further confirmed in the randomized studies. A personal or family history of VTE, existence of hereditary thrombophilia or/and multiple risk factors for VTE represent a strong contraindication to oral HRT use. In such persons the application of transdermal estrogen can be considered after careful individual evaluation of the benefits and risks. Transdermal estrogen should be also the first choice in overweight/obese women requiring HRT