The comparison of the effectiveness and safety of drospirone ethinyl estradiol and ethinyl estradiol cyproterone in the treatment of polycystic ovarian syndrome: A protocol for systematic review and meta-analysis.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is an endocrine disorder syndrome with reproductive dysfunction and abnormal glucose metabolism. Persistent non-ovulation, excessive androgens and insulin resistance are important features and they are the most common causes of menstrual disorders in women during childbearing years. At present, the cause of PCOS is not clinically clear. Current studies suggest that it may be due to the interaction of certain genetic genes with environmental factors. It is an important cause of infertility or early miscarriage with the characteristics of various causes and complex clinical manifestations. At present, for the treatment of PCOS patients, clinical treatment mainly includes hypoglycemia, insulin and menstrual regulation and other symptomatic and supportive treatment. Drospirone ethinyl estradiol and ethinyl estradiol cyproterone are 2 of the most commonly used drugs in clinical treatment of PCOS, but there is lack of the evidence of evidence-based medicine. Therefore, this study systematically evaluates the therapeutic effect and safety of PCOS patients with 2 short-acting oral contraceptives, drospirone ethinyl estradiol and ethinyl estradiol cyproterone, which provides the guidance for clinically selecting the appropriate drug to treat PCOS. METHODS: Searching CNKI, WanFang Data, VIP, SinoMed, PubMed, EMbase, Web of Science, and The Cochrane Library database by computer, collecting the randomized controlled studies of DEE and EEC in the treatment of PCOS. The retrieval time limit is from the establishment of each database to July 1, 2020. In addition, tracing the references incorporated into the literature to supplement to the relevant literature. Using the retrieval method by combining the free words and the subject words, and the individual search of different databases is carried out. Meta-analysis is performed using RevMan 5.3 software after 2 researchers independently screens the literature, extracts the data, and evaluates the bias risk included in the study. RESULTS: This study will systematically evaluate the DEE and EEC in the treatment of PCOS by collecting the required evidence to understand the effects of the 2 drugs on hypersotrophicemia, insulin resistance, lipid metabolism, and the safety during drug use in patients of this class, and the results will be published in highly influential academic journals. CONCLUSION: The results of this study will provide theoretical basis for the drug treatment of polycystic ovarian syndrome and provide help in the decision-making of clinical treatment of the disease. ETHICS AND DISSEMINATION: In this study, meta-analysis was used to conduct a second study on the published literature. Therefore, this type of systematic review research does not need to be approved by ethics. OSF REGISTRATION DOI: 10.17605/OSF.IO/8GW9M.

Scoping review to map evidence on mechanism of action, pharmacokinetics, effectiveness and side effects of centchroman as a contraceptive pill.

OBJECTIVE: To systematically identify and map the available evidence on effectiveness, side effects, pharmacokinetics and mechanism of action of centchroman as a contraceptive pill. INTRODUCTION: Centchroman was introduced in the Indian national family planning programme in 2016 as a once-a-week short-term contraceptive pill/oral contraceptive. At present there are no WHO recommendations on this method of contraception. We examined the available evidence through a scoping review. METHODS: A search was conducted inclusive to the years 1970-2019 on electronic databases, grey literature sources and reference lists of included studies to identify studies. The five stages of Arksey and O'Malley's scoping review framework were applied in undertaking this scoping review. RESULTS: The review identified 33 studies conducted between 1976 and 2017. Two studies reported mechanism of action of centchroman. Pharmacokinetics was reported by five studies among non-breastfeeding women and four studies among breastfeeding women. Eight studies reported on effectiveness ranging from 93% to 100%. Pregnancies due to user failure ranged from 2.6% to 10.2%. Although side effects were reported in 13 studies, the incidence varied greatly between the studies. Continuous bleeding and prolonged cycles >45 days were the most commonly reported side effects. All studies conducted had a small sample size and the duration of follow-up of women was 12 months or less. Fifty-five per cent of studies were by the developers of the pill (Central Drug Research Institute) and results of the phase IV clinical trial were unavailable. CONCLUSIONS: The scoping review shows that studies with robust designs and conducted in international context are lacking. Insufficient evidence exists on centchroman use as a postcoital contraceptive pill. The broad uncertainty in range of side effects and effectiveness in the studies implies insufficient evidence to make global recommendations on centchroman that is currently licensed as a contraceptive in India.

Making OTC Oral Contraceptives Available for All Women.

Sensible legislation has been introduced. It's time to pass it.

Evaluating the practice of Iranian community pharmacists regarding oral contraceptive pills using simulated patients

Background: As oral contraceptive pills are available over the counter in pharmacies, pharmacists are professionally responsible for checking and informing patients about every aspect of taking these drugs. Simulated patient method is a new and robust way to evaluate professional performance of pharmacists. Objective: The aim of the present study was to evaluate the pharmacy practice of Iranian pharmacists regarding over-the-counter use of oral contraceptive pills using simulated patient method. Methods: Simulated patients visited pharmacy with a prescription containing ciprofloxacin and asked for oral contraceptive pills. The pharmacist was expected to ask important questions for using these drugs and to inform the patient about them properly. Moreover, the Pharmacists should advise patients in regard to the possible interaction. Results: Ninety four pharmacists participated in this study. In 24 (25.3%) visits, the liable pharmacist was not present at the time of purchase. Furthermore, In 13 (18.57 %) visits by the simulated patients, the liable pharmacists did not pay any attention to the simulated patients even when they asked for consultation. Twenty nine (41.43%) pharmacists did not ask any question during dispensing. Nausea was the most frequent described side effect by pharmacists (27 (38.57%)). Yet important adverse effects of oral contraceptive pills were not mentioned by the pharmacists except for few ones. Only twelve (17.14%) pharmacists mentioned the possible interaction. There was a significant relation between the pharmacists’ gender and detection of possible interaction (p value= 0.048). Conclusion: The quality of the pharmacists’ consultations regarding the over the counter use of oral contraceptive pills was not satisfactory and required improvement (AU)

No disponible

History of chronic toxicity and animal carcinogenicity studies for pharmaceuticals.

During the 20th century, as drug products were being developed to treat both known and emerging human diseases and conditions, determining the safety of these new chemicals became of increasing importance and necessity. For a time, the safety of use in human populations was of question, let alone whether the drug product was truly effective. As such, US and international regulatory agencies have played a major role in establishing standardized testing to evaluate the safety and efficacy of drug products. Pharmacologic and toxicologic evaluation of a new drug in animals is an important part of the pharmaceutical development process prior to its first-time use in humans, as well as its potential chronic use in affected populations. Just as both science and technology have evolved over the past century and further, so have the guidelines that have been put forth to adequately and efficiently evaluate the toxicity of new drugs and their subsequent safety in humans. This review summarizes the historical highlights of the conduct of drug safety evaluations in animals, particularly with regard to chronic toxicity and carcinogenicity assessments, and how we have progressed to our current standards and protocols to ensure safe use of drug products in human populations.

Prescribing contraception for young women.

BACKGROUND: Since 2002, specially qualified nursing sisters and midwives have had the right to prescribe contraceptive pills for women aged 16 to 19. This arrangement has since been expanded to cover hormonal contraception, with the exception of the hormonal coil. The purpose of this study is to evaluate the arrangement. MATERIAL AND METHOD: The prescription register uses pseudonyms and contains a number of facts about user, medication and prescriber. A database of women born in 1989, totalling 29,821, has been designed as a unit for analysis. RESULTS: 75 and 79% of the cohort had filled at least one prescription for contraceptive pills or hormonal contraception by the end of the calendar year in which they turned 19. Almost 12% had filled at least one prescription for the mini-pill, while far fewer had filled prescriptions for vaginal hormone ring, contraceptive injection, contraceptive patch or hormonal coil. Doctors issued two third of the prescriptions. Nursing sisters wrote more prescriptions than doctors for the age group 17-18. The period of time during which they had been using the contraceptive pill and the mini-pill did not depend on who prescribed them. INTERPRETATION: The fact that close to 80% of the cohort born in 1989 has filled at least one prescription for hormonal contraception shows that there is a high degree of awareness about preventing unplanned pregnancy. Extending the right to write prescriptions to nurses and midwives has increased the availability of contraception, and young women are taking advantage of this option.

Estradiol valerate and dienogest: a novel four-phasic oral contraceptive pill effective for pregnancy prevention and treatment of heavy menstrual bleeding.

Estradiol valerate and dienogest have been combined to create a novel four-phasic oral contraceptive pill effective for both pregnancy prevention and treatment of heavy menstrual bleeding. This formulation represents the only oral contraceptive pill available in the USA containing an estrogen component that is biologically active as the endogenous estrogen 17ß-estradiol. This medication was developed out of efforts to replace the most common estrogen in contraceptive pills, ethinyl estradiol, which is known to be a potent inducer of hepatic protein synthesis. Estradiol valerate has been available since the 1970s in oral and injectable forms indicated for the treatment of menopausal climacteric symptoms. Dienogest has been used in other oral contraceptive pills for over 10 years. Previous attempts to develop an oral contraceptive pill with natural estradiol or estradiol valerate were unsuccessful due to poor cycle control. A novel dynamic-dosing regimen was devised to improve the bleeding pattern. This medication has been shown in several clinical trials to have good contraceptive efficacy and cycle control. Recent studies have also demonstrated that this medication is effective for the treatment of heavy menstrual bleeding. However, compared with other oral contraceptive pills, this medication is associated with a higher frequency of absent withdrawal bleeding. Furthermore, the dynamic dosing regimen requires relatively complex instructions for users who miss pills.

[The statement of Polish Gynecological Society experts on oral use of contraceptive 75 microg desogestrel minipill in different clinical cases--state of art in 2008]. / Stanowisko Zespolu Ekspertów Polskiego Towarzystwa Ginekologicznego dotyczace zastosowania antykoncepcyjnej minitabletki gestagennej zawierajacej 75 microg dezogestrelu w wybranych sytuacjach klinicznych--stan wiedzy na 2008 rok.

Recent epidemiologic studies indicate that use of combined oral contraception is associated with a increase in the incidence of cardiovascular disease (venous thromboembolism, pulmonary embolism, myocardial infarction and stroke). The risk of cardiovascular disease is strongly related to estrogen dose, progestogen type and other factors for example thrombogenic mutations and cigarette smoking among female over age 35. The progestogen only contraception is safe alternative to combined hormonal contraception. Progestogen only pill (POP) has different levels of action (local and/or central) which may vary from one drug to another. As for the cardiovascular disease risk, progestogens are not considered to be risk factors. Desogestrel containing POP is advised in the following cases: bad tolerance of exogenous oestrogens; in order to counteract an endogenous hyperoestrogenosis; medical, metabolic or cardiovascular contraindications to estroprogestogen contraception. Lastly, POP should be used as a prime contraception in some particular situations (breast feeding, endometriosis, adenomyosis, cigarette smoking, contraception for older women). These recommendations present the actual system of care in that population of women in Poland.

Oral contraceptives and venous thromboembolism: which are the safest preparations available?

Oral contraceptive therapy is associated with a fourfold increased risk of venous thromboembolism as compared with age-matched non-users. The composition of oral contraceptives has varied considerably during the past two to three decades. The estrogen content (ethinylestradiol) has decreased and is now less than 0.03 mg/pill. This was done on the assumption that estrogen was the main culprit for thrombotic complications. Subsequently it was found that the progestins contained in the pill could also play a thrombogenic role. This was particularly maintained to be so for the third-generations progestins, namely gestodene or desogestrel. These gonane progestins have been widely used since the early 1990s, because they appeared to have a lesser androgenic effect. A careful and impartial evaluation of the literature seems to indicate that third-generation progestins are associated with a slight increase in thrombotic risk. However, the significance of this difference remains to be proven. In fact, a relative risk of only two in retrospective studies may have limited effect and disappear in prospectives studies. The role of associated risk factors, both congenital and acquired, has been often overlooked in most of the papers dealing with the subject. This may be important. Preparations containing third-generation progestins are probably associated with a slight increase in thrombosis risk. It is the responsibility of the physician to select the preparation most suited for a given patient. As a general rule it may be safe to start with a preparation containing second-generation progestins. However there is no need for "a pill scare" and it does not seem justified to have women already taking pills containing third-generation progestins to switch to other preparations. If a woman taking preparations containing third-generation progestins experience symptoms, it is probably safe to advise that patient not to take any oral contraceptive pill in the future, regardless of the type. The same is true for women who experience symptoms while taking second-generation progestins preparations.

Biphasic versus monophasic oral contraceptives for contraception: a Cochrane review.

BACKGROUND: Side-effects caused by oral contraceptives discourage compliance with and continuation of oral contraceptives. Three approaches have been used to decrease these adverse effects: reduction of steroid dose, development of new steroids, and new formulas and schedules of administration. The third strategy led to the biphasic oral contraceptive pill. We compared biphasic oral contraceptives with monophasic oral contraceptives in terms of efficacy, cycle control and discontinuation due to side-effects. Our a priori hypotheses were: (i) biphasic oral contraceptives are less effective in preventing pregnancy than monophasic oral contraceptives, and (ii) biphasic oral contraceptives cause more side-effects, give poorer cycle control and have lower continuation rates. METHODS: We searched computerized databases Medline, Embase, Popline and the Cochrane Controlled Trial Register. Additionally, we searched the reference lists of all potentially relevant articles and book chapters. We also contacted the authors of relevant studies and pharmaceutical companies in Europe and the USA. We included randomized controlled trials comparing any biphasic oral contraceptive with any monophasic oral contraceptive when used to prevent pregnancy. We examined the studies found during the various literature searches for possible inclusion and assessed their methodological quality using the Cochrane guidelines. We contacted the authors of all included studies and of possibly randomized studies for supplementary information about the study methods and outcomes. We entered the data in RevMan 3.1, imported the data into RevMan 4.1, and calculated Peto odds ratios for the incidence of intermenstrual bleeding, absence of withdrawal bleeding and study discontinuation due to intermenstrual bleeding. RESULTS: Only one trial of limited quality compared a biphasic and monophasic preparation. This trial examined 533 user cycles of a biphasic pill (norethindrone 500 microg/ethinyl estradiol 35 microg for 10 days, followed by norethindrone 1000 microg/ethinyl estradiol 35 microg for 11 days) and 481 user cycles of a monophasic contraceptive pill (norethindrone acetate 1500 microg/ethinyl estradiol 30 microg daily). The study found no significant differences in intermenstrual bleeding, amenorrhoea and study discontinuation due to intermenstrual bleeding between the biphasic and monophasic oral contraceptive pills. CONCLUSIONS: Conclusions are limited by the identification of only one trial, the methodological shortcomings of that trial and the absence of data on accidental pregnancies. However, the trial found no important differences in bleeding patterns between the biphasic and monophasic preparations studied. Since no clear rationale exists for biphasic pills and since extensive evidence is available for monophasic pills, the latter are preferred.

Noncontraceptive benefits of oral contraceptive use: an evidence-based approach.

Numerous noncontraceptive benefits of oral contraceptive (OC) use have been identified. These include a reduction in ovarian and endometrial cancers, functional ovarian cysts, pelvic inflammatory disease, benign breast disease, iron-deficiency, menstrual disorders, dysmenorrhea, bone loss, and acne. The best "evidence" is in the area of cancer prevention, maintenance of bone mineral density (BMD) and the treatment of acne vulgaris. Based on the body of evidence available today, several evidence-based clinical recommendations can be made regarding BMD. In young, reproductive-age women with a hypoestrogenic condition, there is a protective effect on BMD with OC use. In older reproductive-age women with declining ovarian function, there is also a protective effect on BMD with OC use. With long-term use of OCs (greater than 5 years) protection increases with increasing duration of use. There is a high degree of biologic plausibility for the beneficial effect of OC use on states associated with androgen excess, such as acne. Two randomized, placebo-controlled, multicenter clinical trials of a triphasic norgestimate-containing OC were published. Using evidence-based criteria, there is strong evidence that this OC effectively treats acne vulgaris. As further experimental and observational studies are completed, they should substantiate many of the other known benefits; thus, further evidence-based recommendations will be possible.

Safety and efficacy of fertility-regulating methods: a decade of research.

An international venture was launched in 1985 to fill a recognized gap in post-marketing surveillance of fertility-regulating methods. For this purpose a new task force was set up by the Special Programme of Research, Development, and Research Training in Human Reproduction, which is cosponsored by the United Nations Development Programme, the United Nations Population Fund, the World Bank, and WHO. Research priorities were chosen and epidemiological studies inaugurated, involving a total of 47 countries--mostly from the developing world. Important progress has been made, especially in helping to define the beneficial and possible adverse effects of oral contraceptives on the risk of neoplasia; in showing that the injectable contraceptive depot-medroxyprogesterone acetate protects against endometrial cancer and does not increase the overall risk of breast cancer, in clarifying which groups of women are susceptible to the rare cardiovascular complications of oral contraceptives (myocardial infarction, stroke, and venous thromboembolism); and in establishing the long-term effectiveness and safety of intrauterine devices. The research has already made a significant impact on family planning policies and practice. Critical appraisal of this venture, which has been modestly funded, confirms the value of mission-oriented research. It also illustrates the potential of collaboration that bridges the global divide between developing and developed countries.

PIP: This article concerns the essential findings of the task force created by the Special Programme of Research, Development, and Research Training in Human Reproduction in 1985 to conduct research on the safety and efficacy of fertility-regulating methods. The task force had 9 research priorities which include: 1) effects of contraceptive use during lactation; 2) pelvic inflammatory disease and contraception; 3) cardiovascular disease and hormonal contraception; 4) cancer and hormonal contraception; 5) interactions between contraceptive use and disease; 6) morbidity due to female sterilization; 7) induced abortion; 8) safety of Norplant; and 9) IUDs. It then established epidemiological studies in 47 countries, which were mostly from the developing world. Some main achievements were: 1) identification of the beneficial and possible adverse effects of oral contraceptives (OCs) on the risk of neoplasia; 2) demonstrating that injectable depot-medroxyprogesterone acetate protects against endometrial cancer and does not increase the overall risk of breast cancer; 3) clarifying which groups of women are prone to the complications of OCs; and 4) establishing the long-term effectiveness and safety of IUDs. Furthermore, the valuable information produced by this research program has already had a significant impact on family planning policies and practice. This venture also strengthens the value of mission-oriented research and demonstrates the potential of collaborative research between developing and developed countries.

The pill in Japan: will approval ever come?

PIP: The Japanese Ministry of Health and Welfare voted in March 1998 to indefinitely delay the licensing of oral contraceptives in Japan. Over years of attempts to gain approval of the pill for contraception, health officials have cited a range of reasons for their position against the pill, including concern over side effects, fears about the potential spread of sexually transmitted diseases if pill use replaces condom use, and worries about the environmental effects of hormonal contraceptive use. Japan is unique in banning all hormonal methods of contraception. The author describes the history of hormonal agents in Japan, from their initial approval in the country for noncontraceptive therapeutic uses in the late 1950s through the defeat in March 1998. Given the higher failure rates associated with condom use and fertility awareness, it is no wonder that abortion is rather common in Japan. Making hormonal methods of contraception available would help to prevent unwanted pregnancies. The uphill battle to legalize the low-dose pill in Japan continues.^ieng

Contraceptive use in women with bacterial vaginosis.

The aim of the study was to investigate if bacterial vaginosis (BV) is associated with use of specific contraceptives. Women at family planning and youth clinics (n = 956), among whom 131 had BV, were subjects for structured in-depth interviews including current and previous contraceptive use. Variables measuring sexual risk-taking were ascertained. Current users of contraceptives were compared with non-users. Both oral contraceptive (OC) and condom use showed a significant protective effect against BV, adjusted for possible confounders (odds ratios were 0.4 and 0.3, respectively). Intrauterine device use (IUD) showed no association with BV. Women with BV had less often used any contraceptives, including condom, at their sexual debut than the women in the comparison group. In this study, OC and condom use seemed to exert a protective effect against BV, whereas no effect for IUD use was found.

PIP: To determine whether bacterial vaginosis (BV) is associated with use of specific contraceptive methods, 956 women from family planning and youth clinics at 3 Swedish hospitals were enrolled in a cohort study. 131 women had at least 3 of the 4 clinical signs of BV: a homogenous gray vaginal discharge, a vaginal pH of 4.7, a positive amine test, and the presence of "clue" cells. Age at first intercourse was 16 years among those with and without BV; however, 8.4% of women with BV, compared with only 1.7% of controls, had had more than 1 sex partner in the last 6 months. Other factors associated with BV were more than 10 lifetime sex partners, non-use of contraception at first intercourse, a history of sexual abuse, an induced abortion, smoking, and alcohol consumption. After adjustment for sexual risk-taking, there was a significant negative association between BV and oral contraceptive (OC) use (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.2-0.8). There was also a significant negative association with condom use (OR, 0.3; 95% CI, 0.1-0.9). There was no association between BV and IUD use, before or after adjustment for confounding factors. Insufficient numbers of diaphragm or spermicide users were available for analysis. The finding of an apparently protective effect against BV of OCs and condoms lacks a biological explanation at present, although it is speculated that OC use increases the glycogen content of vaginal epithelial cells, in turn inhibiting the in vitro growth of certain bacteria.