Contraception

Methotrexate (MTX) is one of the most commonly used drugs in the treatment of inflammatory rheumatic diseases. Unfortunately, MTX is an FDA Pregnancy Category X medication, which means it is contraindicated during pregnancy. The following review of the literature, with international guidelines, gives in addition an overview of current scientific knowledge on the topic. MTX is a teratogenic substance. It accesses the placenta and, for the dosage of 5 to 25 mg per week normally used in rheumatic diseases, can lead to both habitual abortions and anomalies in the neonate. Folic acid antagonism of MTX is the reason. In the rheumatologic setting, small case reports are available for the usage of MTX of 101 pregnant women at the time of conception or during pregnancy, mostly during the first trimester. Individual casuistry also exists. An abortion rate of 23% was found to result from these case reports. The anomaly rate for neonates was >5%. Only a few pregnancies with neonatal anomalies are described with the child’s father taking MTX at the time of conception. MTX is taken up (in small amounts) by the mother’s milk, and breast feeding under MTX therapy, therefore, is also contraindicated. Detailed and exact information on female patients taking MTX during the reproduction phase, but also for the father-to-be of the child if treated with MTX, with reference to the required contraception until at least three months before a planned conception and stopping of MTX at least at that time, is essential.

A significant number of women, especially in developing countries, need protection against more than one sexually transmitted infection (STIs), for instance HIV-1 and HSV-2, and family planning methods to prevent unwanted pregnancies. Dual protection technologies (DPTs; also known as multipurpose technologies) are designed to address two different indications with one product. Examples of DPTs are vaginal products capable of preventing transmission of HIV-1 in women while simultaneously providing contraceptive properties and a vaginal product capable of reducing HIV-1 transmission while preventing transmission of a second STI. DPTs can be categorized into three main approaches: 1) physical barriers, 2) chemical barriers, and 3) a combination of physical and chemical barriers. Examples of physical barriers are male and female condoms, diaphragms and cervical caps. Chemical barriers include use of a single drug with two mechanisms of action (viz., dual-activity compounds with microbicidal and contraceptive properties or activity against HIV-1 and a second STI pathogen such as HSV-2) or a combination of two drugs each targeted against separate mechanisms for achieving contraception and inhibition of HIV-1. Combinations of chemical and physical barriers are based on physical barriers such as a diaphragm along with a microbicide. Examples of each approach and current prototypes (such as vaginal gels and intravaginal rings) under development are described in this paper. Challenges facing development and regulatory approval of DPTs are also reviewed. This article forms part of a special supplement on a presentation covering DPTs, based on the symposium “Trends in Microbicide Formulations”, held on 25 and 26 January 2010, Arlington, VA.

Vaginal ring devices capable of providing sustained/controlled release of incorporated actives are already marketed for steroidal contraception and estrogen replacement therapy. In recent years, there has been considerable interest in developing similar ring devices for the administration of microbicidal compounds to prevent vaginal HIV transmission. Intended to be worn continuously, such coitally independent microbicide rings are being developed to maintain effective vaginal microbicide concentrations over many weeks or months, thereby overcoming issues around timing of product application, user compliance and acceptability associated with more conventional semi-solid formulations. In this article, an overview of vaginal ring technologies is presented, followed by a review of recent advances and issues pertaining to their application for the delivery of HIV microbicides. This article forms part of a special supplement on presentations covering intravaginal rings, based on the symposium “Trends in Microbicide Formulations”, held on 25 and 26 January 2010, Arlington, VA.

INTRODUCTION: Because of their safety and efficacy oral contraceptives are available without prescription in many countries. Monophasic combined oral contraceptives are a combination of estrogen and progestin taken in constant amounts. VENOUS THROMBOEMBOLISM: Combined oral contraceptives slightly increase the risk of venous thromboemolism, but this event is very rare among non-pregnant women of reproductive age. The absolute risk rises with age, obesity, recent surgery and certain forms of thrombophilia. The estrogen component of combined oral contraceptives increases the synthesis of several coagulation factors in a dose-dependent manner. Changes of most of these parameters are very small and there is no evidence that they have any effect upon the clinical risk of developing venous thrombosis. If a woman has an inherited coagulation disorder that increases her risk of developing thrombosis, the risk is increased several fold if she ingests estrogen containing oral contraception. CONCLUSION: The increased risk of venous thromboembolism associated with combined oral contraceptives should have little impact on healthy women, but may have substantial impact on women with a history of thromboembolism. Combined oral contraceptive use increases the risk of venous thromboembolosm in a dose-dependent manner. The absolute risk of venous thromboembolism rises with age, obesity, recent surgery and certain forms of thrombophilia, as well.