Human Papillomavirus Infections and Cervical Carcinoma

Karcinom vrata maternice drugi je najčešći karcinom u žena u svijetu. Najveća incidencija ove bolesti u nerazvijenim je zemljama jugozapadne Afrike, Južne Amerike i jugoistočne Azije. U Europi najveća incidencija ove bolesti je u zemljama istočne Europe. Hrvatska ima nižu incidenciju ove bolesti od mnogih država srednje i jugoistočne Europe. Karcinom vrata maternice bolest je mlađih žena. Veliko istraživanje International Agency for Research on Cancer (IARC) iz 1995. godine otkrilo je u 99,7% svih karcinoma vrata maternice genom humanog papilomavirusa (HPV). Genitalni sojevi HPV-a podijeljeni su u tri skupine: sojevi visokog onkogenog rizika, mogući karcinogeni sojevi i sojevi niskog onkogenog rizika. Sojevi 16 i 18 odgovorni su za oko 70% karcinoma cerviksa podrijetla pločastih stanica i oko 86% adenokarcinoma vrata maternice. Infekcija HPV-om danas je najčešća spolno prenosiva bolest. 90–95% slučajeva infekcija HPV-om prolazi spontano. Za razvoj preinvazivnih lezija vrata maternice (CIN – cervikalna intraepitelna neoplazija) i potom karcinoma potrebna je trajna infekcija visokoonkogenim sojevima HPV-a. Pretpostavka je da od trajne infekcije HPV-om do invazivnog karcinoma vrata maternice treba proći 7–10 godina, što ostavlja dovoljno vremena za prevenciju. Teoretski karcinom vrata maternice bolest je od koje ni jedna žena ne bi smjela oboljeti, a kamoli umrijeti. Ipak incidencija ove bolesti “stabilna” je. Razlog tomu je oportunistički program probira u Hrvatskoj. Na PAPA-obrisak uglavnom dolaze uvijek iste žene individualnom inicijativom. Stoga se nameće potreba organiziranog programa probira. Prošle godine u mnogim zemljama registrirano je cjepivo protiv HPV-a. Organizaciju nacionalnih imunizacijskih programa moguće je aplicirati samo u zemljama s dobro organiziranim programima sekundarne prevencije i u zemljama koje to mogu platiti.Cervical carcinoma is the second most frequent carcinoma in women worldwide. The highest incidence is recorded in developing countries of southwest Africa, South America and Southeast Asia. In Europe, the highest incidence is recorded in eastern European countries. In Croatia, its incidence is lower than in many CEE countries. Cervical carcinoma is the disease of young women. The major study conducted by the International Agency for Research on Cancer (IARC) in 1995 revealed that 99.7% of all cervical carcinoma cases could be attributed to human papillomavirus (HPV). Genital HPV strains are divided into three groups: high oncogenic risk strains, potentially carcinogenic strains, and low oncogenic risk strains. Strains 16 and 18 are responsible for about 70% of cervical epithelial cancers, and about 86% of cervical adenocarcinomas. Nowadays the HPV infection is the most frequent sexually transmitted disease. Remission can be spontaneous in 90-95% of HPV cases. Pre-invasive cervical lesions (CIN - cervical intraepithelial neoplasia) and subsequent carcinoma develop after a persistent infection with highly oncogenic HPV strains. The presumed interval between a persistent HPV infection and invasive cervical carcinoma is seven to ten years, which leaves suffi cient time for prevention. Theoretically, no woman should develop cervical carcinoma, or let alone die. However, the incidence of cervical carcinoma is stable. The reason is opportunistic screening in Croatia. These are mostly the same women who have Pap smears, and it is on their own initiative. Therefore, there is a need for organized screening program. Last year, HPV vaccine was registered in many countries. National immunization programs can be realized only in countries with well-organized secondary prevention and fi nancial prerequisites

Ovarian thecoma in adolescent – a rare case of hirsutism

The main goal of managing hirsutism in adolescent girls is to distinguish familial idiopathic hirsutism from endocrinological disorders such as PCOS and androgen-secreting tumors. The latter account for <0.02% cases and typically present with rapidly progressing hirsutism, virilization and elevation of serum androgens. Some rare benign ovarian tumors have a slow progression and long duration of symptoms before diagnosis. Ovarian thecomas typically occur in postmenopausal women but few cases have been reported in adolescence. Thecomas are almost always estrogenic; 10% of the luteinized forms are androgenic. They are usually clinically benign, although several have been reported malignant in literature

Diseases and Destinies of Famous Composers Why should one even write about composers’ diseases?

Why should one even write about composers’ diseases? That question is no longer an issue because in the last 50 to 100 years, this very topic has given us a whole new insight into famous composers’ creative lives. Grieg, as well as many others, concurred. The very goal of biopathographies is to investigate the lives and creativity of famous composers from the psychological as well as from medical point of view. We attempted to list and interpret the data we found accurately, and categorize them using a simple everyday vocabulary in the book Diseases and Destinies of Famous Composers.

Croatian composers’ diseases – biopathographies

Presentation of the diseases among 25 significant croatian composers reveals some infectious diseases (tuberculosis, etc.) among the composers who had died young and some chronic non-infectious diseases (mostly malignant, inflammatory and cardiocerebral origin) among composers who died in old age. It is a part of the pathographic review of over 300 composers from the book »Diseases and destinies of famous composers«

Cervical Cancer as a Public Health Issue – What Next?

Cervical cancer is the second most common cancer in women worldwide. There are about 60,000 newly detected cases and 30,000 deaths annually in Europe, with the highest incidence reported from Eastern Europe countries. According to data from the National Institute of Public Health, in Croatia the incidence of cervical cancer was 14.9/100,000 in 2006, ranking eighth most common malignancy in women. Croatia has a lower incidence of the disease compared to many countries of Central and Southeast Europe. A large study carried out in 1995 by the International Agency for Research on Cancer, which included cervical cancer material collected from 22 countries all over the world revealed HPV genome in 99.7% of cases. Efficient methods of cervical cancer detection and screening methods for identification of precancerous lesions (conventional Pap smear) are available. Cervical cancer prevention programs should include education (of health care providers and women), stressing the benefits of screening, the age of the peak cervical cancer incidence, and the signs and symptoms of precancerous lesions and invasive disease. The aim of screening actions is to detect precancerous lesions that may lead to cancer if left untreated. Screening can only be effective if there is a well-organized system of follow up, diagnosis and treatment. Cervical cytology, or Papanicolaou (Pap) testing, has for decades been a cornerstone of cervical cancer screening. According to recent guidelines issued by the World Health Organization Regional Office for Europe, the primary task of the public health system is the introduction of secondary prevention through properly organized screening programs. Launching the national immunization program is only possible in the countries with well-organized secondary prevention programs and in those that can afford it

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

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

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