Propranolol concentrations in plasma after insertion into the vagina.

Six healthy women participated in a study of the concentrations of propranolol achieved in plasma after insertion of the drug into the vagina. In four of the women the concentrations were also determined after administration by mouth. The area under the concentration curve for propranolol administered per vaginam was significantly greater than that after oral administration. There were small significant reduction in systolic blood pressure, pulse rate, and forced expiratory volume in one second after vaginal administration but these did not cause any symptomatic side effects. The tolerability of the vagina to drugs and the safety of this form of treatment remain to be determined. Probably further studies of the contraceptive effects of propranolol should be conducted with the dextro isomer of the drug.     

Progestin-only contraceptive rings

Several progestin-only long acting contraceptives are currently available in the form of implants or injectables. Vaginal rings are another contraceptive option in the final stages of development. These steroid-containing polymer rings are placed in the vagina, providing relatively constant drug release, thus allowing for lower effective doses. Vaginal rings have the advantage of being user-controlled and non-provider dependent, and their use is non-coital related. The first clinical study with medroxyprogesterone acetate vaginal rings was published in 1970. Since then numerous clinical trials testing different steroids and doses have followed. A large Phase III multicenter clinical trial with a levonorgestrel ring, releasing 20 microg/day, was coordinated and sponsored by WHO. The cumulative one-year pregnancy rate was 4. 5%. The principal reasons for discontinuation were menstrual disturbances (17.2%), followed by frequent expulsion of the ring (7. 1%), and vaginal symptoms (6.0%). The finding of erythematous lesions in the vagina in some women has led to the development of a more flexible device. Collaboration with industry should facilitate the manufacture of a redesigned levonorgestrel ring with a higher release rate. The Population Council is also developing a vaginal ring containing Nestorone for 6 months of continuous use. Ovulation inhibition was achieved in over 97% of the segments studied, with rings releasing either 50, 75, or 100 microg/day. No pregnancies occurred in women using the low-dose ring, while one pregnancy each occurred in the intermediate- and high-dose ring groups for a 6-month cumulative pregnancy rate of 0.0, 1.9, and 2.1%. Bleeding irregularities were common. Nestorone is orally inactive; therefore this ring is also excellent for use in lactating women.     

Vaginal rings for contraception in lactating women

Contraceptive methods for breastfeeding women should be safe for the mother and infant and should not interfere with lactation. Progestin-only methods meet these conditions and can be used from the sixth week postpartum. Because all progestins are excreted in milk, those that are insufficiently active by the oral route are preferable to avoid any possible effect on the baby. These steroids, however, must be administered to the mother by a non-oral route. Initially, progesterone was administered subdermally to test this concept. Subsequently, a progesterone vaginal ring was developed to be used continuously for 3 to 4 months and replaced with a new device, as needed, until weaning. Clinical trials have shown a high contraceptive efficacy (over 98.5%) and safety. The gross continuation rate of this method is approximately 40% at 12 months of use, with use-related problems being the main reason for discontinuation (26.8%). Currently, a Nestorone vaginal ring is under development, delivering 50 microg of Nestorone per day. It may be used continuously for up to one year, even if weaning occurs earlier. Both of these progestin-only rings prolong lactational amenorrhea to 10 to 12 months, which represents a health benefit and convenience for many women. The registration of the progesterone vaginal ring, developed as a contraceptive method to be used exclusively during lactation, has been approved in Chile and Perú. The fact that it is a user-controlled long-term contraceptive that delivers a natural hormone makes it an attractive option for many women.     

Norethisterone oenanthate as an injectable contraceptive: use of a modified dose schedule.

Norethisterone oenanthate (NET-OEN) was given as an injectable contraceptive to 295 healthy women over 1606 woman-months. A modified injection schedule was used. There were no pregnancies, and the 12-month, life-table, use-related discontinuation rate was 39.1/100 users. Menstrual disturbance (10.8/100 women), minor side effects (13.5/100 women), and personal reasons (12.0/100 women) were the main causes of use-related discontinuation. There was no difference in use-related discontinuation rates between women receiving their first injection during a normal menstrual period and those receiving it immediately after a pregnancy. There were no serious side effects. The use of NET-OEN in certain groups of women is recommended, particularly in those in need of highly effective contraception, who cannot or do not wish to take oral contraceptives, who are lactating, or who are awaiting hospital admission for sterilisation.     

胎膜早破与孕妇阴道微生态 及血清IL-10、IL-22、NF-κB的相关性

摘要：目的 探讨胎膜早破与孕妇阴道微生态及血清IL-10、IL-22、NF-kB的相关性。方法 选取我院妇产科收治的84例胎膜早破孕妇为胎膜早破组,100例正常孕妇为正常孕妇组及100例正常未怀孕妇女为正常妇女组。比较3组对象阴道分泌物各细菌阳性率、阴道微生态状态及各组间血清IL-10、IL-22、NF-kB水平。对胎膜早破孕妇阴道微生态失衡与血清IL-10、IL-22、NF-kB水平进行Pearson相关性分析。结果 胎膜早破组孕妇阴道乳杆菌（79.8%）、大肠埃希菌（48.8%）、溶血葡萄球菌（22.6%）检出率均显著高于正常孕妇组和正常妇女组（均P<0.05）。胎膜早破组患者阴道pH（6.87±0.75）、阴道微生态失衡率（40.5%）均显著高于正常孕妇组和正常妇女组,H2O2阳性率（11.9%）低于正常孕妇组（21.0%）和正常妇女组（23.0%）,差异均有统计学意义（均P<0.05）。胎膜早破组孕妇血清IL-10、IL-22、NF-kB水平[（51.28±6.58）pg/mL、（45.91±7.13）pg/mL、（30.47±3.27）ng/mL]均显著高于正常孕妇组和正常妇女组。经过Pearson相关性分析,IL-10、IL-22、NF-kB水平与胎膜早破孕妇阴道微生态失衡呈正相关（r=0.657、0.692、0.732,P<0.05）。结论 孕妇阴道微生态环境发生改变引起阴道菌群失调及血清免疫因子的变化,可能是引发胎膜早破的作用机制之一。     

Genital Yeast Infections

Genital yeast infection was studied in 533 women seen in a department of venereology. Yeasts were recovered in culture from 138 patients (26% of the total). Candida albicans accounted for 112 (81%) of the isolates and Torulopsis glabrata for 22 (16%); other yeasts were uncommon. There was no evidence that the presence of yeasts was related to age. 32% of the women who were taking an oral contraceptive harboured yeasts, compared with 18% of those who were not.The symptoms and signs of the women with yeast infections were compared with those with vaginal trichomoniasis and those with no evidence of genital infection. It seems that a clinical diagnosis of vaginal mycosis cannot be made with accuracy and that positive identification of yeasts is necessary; for this, cultural methods are the most satisfactory.     

Correlative relationship between adherence of Candida albicans to human vaginal epithelial cells in vitro and candidal vaginitis

This study investigated whether a correlation exists between predisposition to candidal vaginitis and adherence of Candida albicans to vaginal epithelial cells in vitro. Vaginal epithelial cells from 120 fecund women who were pregnant and/or diabetic had a greater propensity to bind C. albicans than did 71 oral contraceptive users and 75 non-pregnant, non-diabetic controls. The highest level of adherence occurred in pregnant diabetic women. Among 48 non-diabetic postmenopausal females, C. albicans adherence was lower than for fecund controls, but it was higher for cells from 33 postmenopausal diabetic women. The hormonal status of the fecund and postmenopausal women was assayed cytologically by the Karyopyknotic and Maturation Indices, which determine the ratios of superficial, intermediate and parabasal vaginal epithelial cells. Our findings point to increased C. albicans adherence in situations where there is an increase in the number of intermediate epithelial cells: pregnancy, the first or fourth weeks of the menstrual cycle, or diabetes. The adherence of 41 C. albicans isolates from patients with vaginitis was significantly higher than that of 36 isolates from asymptomatic carriers.     

Studies on safety aspects of contraceptive Magainin-A in rabbits.

We have previously reported the contraceptive potential of Magainin-A in rats and rabbits under in vitro and in vivo condition. In this report we evaluated the effect of Magainin-A on the structural organisation of vaginal epithelium in rabbits. The effect of this compound on the erythrocytes and its rate of absorption and clearance from systemic circulation was also studied. The effective contraceptive dose of Magainin-A (1 mg) when administered intra-vaginally for five consecutive days did not induce any structural or morphological abnormalities in vaginal epithelial cells. No adverse effect was observed on the erythrocytes. The rate of Magainin-A absorption and clearance from the circulation was found to be rapid. These results suggest that Magainin-A may be used as a safe intra-vaginal contraceptive compound in future.     

Clinical and Laboratory Findings in a Trial of Norgestrel,a Low-dose Progestogen-only Contraceptive

Norgestrel, a progestogen-only oral contraceptive, was given continually at a dose of 75 μg/day to 144 women of proved fertility. It was an efficient contraceptive with a failure rate of 2·1% (assessed by the “life-table” method) within the first 12 cycles and 3·6% within the first 30 cycles (or 2·0 conceptions per 100 woman-years when assessed by the Pearl index). The overall conception rate for the entire trial period was 2·1% and 1·3 pregnancies per 100 woman-years respectively. Norgestrel caused a high proportion of irregular and generally short bleeding intervals, about one-fifth of the cycles lasting less than 17 days. This irregularity appeared to be due to individual variance in cycle length between women rather than that between their successive cycles. No confirmed instances of thromboembolism were observed. Norgestrel apparently exerts its contraceptive action by several mechanisms: reduction in the sperm penetrability of the cervical mucus and an impairment of luteal function appear important. The serum concentrations of cholesterol and globulin were significantly reduced in women taking norgestrel. Preliminary observations suggest that on discontinuing the medication fertility is promptly restored. Of the 144 women originally enrolled 57 (40%) withdrew for reasons connected with the method before completing 30 months on trial, over half of them because of the irregular menstrual pattern. Nonetheless, in view of its main clinical and laboratory characteristics and simple mode of administration, norgestrel appears to be a useful alternative to the combined type of pill for women unsuitable for, or unable to tolerate, oestrogen-containing preparations.     

Barriers to the use of modern contraceptives and implications for woman-controlled prevention of sexually transmitted infections in Madagascar

Globally, unplanned pregnancies and sexually transmitted infections (STIs) persist as significant threats to women's reproductive health. Barriers to the use of modern contraceptives by women might inhibit uptake of novel woman-controlled methods for preventing STIs/HIV. Use of modern contraceptives and perceptions and attitudes towards contraceptive use were investigated among women in Antananarivo, Madagascar, using qualitative research. The hypothetical acceptability of the diaphragm--a woman-controlled barrier contraceptive device that also holds promise of protecting against STIs/HIV--was assessed. Women consecutively seeking care for vaginal discharge at a public health clinic were recruited for participation in a semi-structured interview (SSI) or focus group discussion (FGD). Audiotaped SSIs and FGDs were transcribed, translated and coded for predetermined and emerging themes. Of 46 participating women, 70% reported occasional use of male condoms, mostly for preventing pregnancy during their fertile days. Although women could name effective contraceptive methods, only 14% reported using hormonal contraception. Three barriers to use of modern contraceptives emerged: gaps in knowledge about the range of available contraceptive methods; misinformation and negative perceptions about some methods; and concern about social opposition to contraceptive use, mainly from male partners. These results demonstrate the need for programmes in both family planning and STI prevention to improve women's knowledge of modern contraceptives and methods to prevent STI and to dispel misinformation and negative perceptions of methods. In addition, involvement of men will probably be a critical component of increased uptake of woman-controlled pregnancy and STI/HIV prevention methods and improved health.     

Contraceptive practice of Irish married and single first-time mothers

This study surveys 100 married and 100 unmarried primiparous mothers, attending the National Maternity Hospital, Dublin, with regard to their contraceptive practice, their planning of their pregnancy and the timing of their first antenatal visit. Nineteen per cent of the married women, but 64% of the unmarried women, had never used any contraceptive method. The contraceptive pill was the most popular method for both groups, but while three in five of the married women had at some time used the pill, only a little more than one in five of the unmarried women had ever used it. One quarter of the women who had used contraception reported that their pregnancy was the result of a failure in their contraceptive method. Eighty-nine per cent of the single group and 20% of the married had not planned their pregnancy. None of the married women, but almost a quarter of the single, delayed their first antenatal visit until after they were 20 weeks pregnant.     

Peripheral blood flow in menopausal women who have hot flushes and in those who do not.

OBJECTIVE--To compare blood pressure, heart rate, and peripheral vascular responsiveness in menopausal women who have hot flushes and in those who do not, and to assess the effect on these variables of treating women who have hot flushes with oestriol, a natural oestrogen, given vaginally. DESIGN--An open, non-randomised cohort study of flushing and non-flushing menopausal women. A before and after investigation of the effects of vaginal oestriol treatment on the circulation. SETTING--Referral based endocrinology clinic. PATIENTS--88 Consecutive menopausal women, 63 complaining of frequent hot flushes and 25 who had not flushed for at least a year. INTERVENTION--Treatment with vaginal oestriol 0.5 mg at night for six weeks in 18 of the women who had hot flushes. MEASUREMENTS AND MAIN RESULTS--Peripheral blood flow was measured by venous occlusion plethysmography at rest and in response to stressful mental arithmetic and anoxic forearm exercises. Blood flow in the forearm and its variability were significantly higher in flushing than in non-flushing women (4.1 (SD 1.7) and 3.1 (0.9) ml/100 ml tissue/min and 17% and 13% respectively). Blood pressure, heart rate, and blood flow in the hand were, however, similar in the two groups. No difference was found in the peripheral incremental response to either stress or anoxic exercise. Vaginal oestriol significantly lowered forearm blood flow from 4.4 (1.5) to 3.3 (1.1) ml/100 ml tissue/min but dilator responsiveness was unaffected. CONCLUSIONS--The peripheral circulation is different in menopausal women who have hot flushes compared with those who do not, with selective vasodilatation in the forearm. The lowered blood flow in the forearm after vaginal oestriol in flushing women may be relevant to the alleviation of vasomotor symptoms induced by oestrogen treatment.     

HIV incidence remains high in KwaZulu-Natal, South Africa: evidence from three districts

Background

HIV prevalence and incidence among sexually active women in peri-urban areas of Ladysmith, Edendale, and Pinetown, KwaZulu-Natal, South Africa, were assessed between October 2007 and February 2010 in preparation for vaginal microbicide trials.

Methodology/Principal Findings

Sexually active women 18–35 years, not known to be HIV-positive or pregnant were tested cross-sectionally to determine HIV and pregnancy prevalence (798 in Ladysmith, 1,084 in Edendale, and 891 in Pinetown). Out of these, approximately 300 confirmed non-pregnant, HIV-negative women were subsequently enrolled at each clinical research center (CRC) in a 12-month cohort study with quarterly study visits. Women in the cohort studies were required to use a condom plus a hormonal contraceptive method. HIV prevalence rates in the baseline cross-sectional surveys were high: 42% in Ladysmith, 46% in Edendale and 41% in Pinetown. Around 90% of study participants at each CRC reported one sex partner in the last 3 months, but only 14–30% stated that they were sure that none of their sex partners were HIV-positive. HIV incidence rates based on seroconversions over 12 months were 14.8/100 person-years (PY) (95% CI 9.7, 19.8) in Ladysmith, 6.3/100 PY (95% CI 3.2, 9.4) in Edendale, and 7.2/100 PY (95% CI 3.7, 10.7) in Pinetown. The 12-month pregnancy incidence rates (in the context of high reported contraceptive use) were: 5.7/100 PY (95% CI 2.6, 8.7) in Ladysmith, 3.1/100 PY (95% CI 0.9, 5.2) in Edendale and 6.3/100 PY (95% CI 3.0, 9.6) in Pinetown.

Conclusions/Significance

HIV prevalence and incidence remain high in peri-urban areas of KwaZulu-Natal.     

Contraception with progestogens and progesterone during lactation

The growth and development of breastfed infants whose mothers used the contraceptive implants Norplant® containing levonorgestrel and the injectable containing norethisterone enanthate were studied. Each group comprised of 120 women who initiated the use during the 5th to 7th week postpartum and were compared with a similar number of IUD using mothers. The breastfeeding performance did not differ between groups. The infants of the three groups performed similarly as regards their physical growth and health as well as the time of acquisition of the various milestones of psychomental development. A vaginal ring releasing 10 mg of the “natural” progesterone per 24 h was tested in breastfeeding mothers. The continuous use of the ring produced a serum level of progesterone around 4 ng/ml. This was effective in augmenting lactational infertility even through the later phases of breastfeeding when such an effect starts to wane off. The use of the ring proved to be acceptable and had no ill-effect on breastfeeding or infant growth or health. Using the natural progesterone as a contraceptive adds a new measure of safety, since the amount of the steroid secreted in the mother's milk will not be effectively absorbed from the infant's gut. These studies suggest the possibility of using two new methods for breastfeeding mothers; Norplant and the progesterone vaginal contraceptive ring. These can be initiated early postpartum, whenever this is considered needed.     

Nestorone: clinical applications for contraception and HRT

The 19-nor derivatives of progesterone are referred to as "pure" progestational molecules as they bind almost exclusively to the progesterone receptor (PR) without interfering with receptors of other steroids. In this category is Nestorone, which has strong progestational activity and antiovulatory potency with no androgenic or estrogenic activity in vivo. These properties make it highly suitable for use in contraception and hormonal therapy (HT). Due to its high potency, very low doses of Nestorone may be delivered via long-term sustained-release delivery systems. Nestorone, 75 or 100 microg per day, released by vaginal ring has suppressed ovulation in women, with inhibition of follicular maturation. A vaginal ring releasing both 150 microg of Nestorone and 15 microg of ethinyl estradiol per day has effectively suppressed ovulation for 13 consecutive cycles. Nestorone has also been used effectively in a single implant for contraception in breastfeeding women and shows promise for use in transdermal systems as a contraceptive or for HT when combined with estrogen.     

Inhibition of embryo implantation in mice through vaginal administration of a proprotein convertase 6 inhibitor

Uterine proprotein convertase 6 (PC6) plays a critical role in embryo implantation in both mice and women. It was hypothesized that inhibiting uterine PC6 could prevent pregnancy. Vaginal administration of a PC6 inhibitor presents the ideal route for local drug delivery. A peptide-based PC6 inhibitor, C-30k-PEG Poly R that was previously shown to have properties of increased vaginal absorption and penetration was tested for its contraceptive potential in mice following vaginal administration. The study demonstrated that this approach could inhibit embryo implantation in some mice (24% completely and 47% partially inhibited).     

Use of Contraception and Attitudes towards Contraceptive Use in Swedish Women - A Nationwide Survey

ObjectiveTo describe contraceptive use and attitudes towards contraceptive use in Sweden which has the highest abortion rate in Western Europe. Secondary objectives were to investigate knowledge of contraceptive methods and outcomes of unplanned and unwanted pregnancies.DesignTelephone survey.SettingNational survey of women living in Sweden.PopulationWomen between 16 and 49 years.MethodsThe survey contained 22 questions with free text and multi choice answers on demographics, contraceptive use, knowledge of and attitudes towards contraception, the importance of monthly bleeding and experience of unintended pregnancy.ResultsA total of 1001 women participated in the survey. Of all women, 721/1001 (72.1%) currently used contraception whereas 268/1001 (26.8%) women did not. Long acting reversible contraception, (LARC; implant and intra uterine contraception) was used by 24.3% of women. The unmet need of contraception in Sweden was estimated at 8.9% (89/1001 women). A total of 781 (78%) women had never experienced an unintended pregnancy whereas 220 (22%) women had had at least one unintended pregnancy. Users and non-users alike stated that one of the most important characteristics of a contraceptive method is its effectiveness.ConclusionsSweden has a large unmet need for contraception. Furthermore, a large proportion of women have experienced at least one unintended pregnancy. Increasing contraceptive use and promotion of LARC is a possible way forward in the effort to reduce the rates of unwanted pregnancies.     

Subdermal contraceptive implants

Subdermal contraceptive implants involve the delivery of a steroid progestin from polymer capsules or rods placed under the skin. The hormone diffuses out slowly at a stable rate, providing contraceptive effectiveness for 1–5 years. The period of protection depends upon the specific progestin and the type of polymer. Advantages of progestin implants include long term contraceptive action without requiring the user's or provider's attention, low dose of highly effective contraception without the use of estrogen, and fertility is readily reversible after the removal of implants. The levonorgestrel implant Norplant R system is the only one that has been approved for distribution. The contraceptive efficacy of Norplant is the highest observed amongst the most effective methods with an annual pregnancy rate of 0.2 during the first and second year and 1.1 on the fifth year. Menstrual problems are the main reason for the discontinuation of Norplant and 9% of women stopped using it during the first year of treatment. Other implants are still under development trying to simplify the method by reducing the number of units and to introduce other progestins that may minimize side effects. Norplant-2 was designed to release the same dose of progestin from only two covered rods. Evaluation of 1400 women enrolled, indicates that over 2 years the cumulative pregnancy rate is below 0.5 per 100 women. There are three single implants under development: Nestorone, 3-Keto-desogestrel and Uniplant that are expected to be effective for 1–2 years. Phase II clinical trials with Nestorone have been completed and no pregnancies have been observed in 1570 woman-months of use. Bleeding irregularities occurred in 20–30% of the women but there were only four terminations because of bleeding problems. A multricentric study is ongoing with a newly designed 3-keto-desogestrel implant named Implanon, which releases approx. 60 μg/day of the hormone. The objectives of this study are to assess contraceptive efficacy, safety and acceptability of Implanon. Another multricentric study is ongoing with Uniplant, which releases nomegestrol acetate with a duration of action for only 1 year. The objectives of the trial are to study the endocrine profile of Uniplant users and to evaluate the efficacy and acceptability of the method.     

A field study of the choice and continuity of use of three contraceptive methods in a rural area of Thailand

A field study was conducted in order to determine the preference for and the continuation rates achieved with 2 previously available contraceptives (the OC and the IUD) and a newly introduced method (depromedroxyprogesterone acetate, or DMPA) in a rural area of Thailand. Women were offered a free choice of method after the presentation of balanced educational material. 73.8% of all women chose DMPA; this preference was not influenced by the educational lecture. 16.9% of the women chose the OC and 9.3% chose the IUD. Women perceived the injection as a convenient method when compared to the OC and the IUD, but the primary preference for DMPA appeared to be mostly due to ill-defined personal factors and the influence of friends. The 1-year life-table continuation rates with DMPA (75.5%/100) women were significantly higher than the continuation rate achieved with the IUD (66.5/100 women). The continuation rates with the OC were 72/100 women, but the excessively high loss to follow-up with the OC made interpretation of results difficult. When women are offered a free choice of contraceptive methods under a quasiexperimental situation, useful information can be gathered on the potential value of new methods for an ongoing family planning program.     

Influence of contraceptive pill and menstrual cycle on serum lipids and high-density lipoprotein cholesterol concentrations.

The fluctuations of serum lipid and lipoprotein concentrations within one cycle were studied both in women using and not using oral contraceptives. High-density lipoprotein cholesterol decreased significantly from 1.47 mmol/l (57 mg/100 ml) to 1.30 mmol/l (50 mg/100 ml) during one contraceptive cycle in eight women and rose again to the initial value during the pill-free days. The mean concentration of total cholesterol also fell significantly as a result of the decrease of high-density lipoprotein cholesterol and of a not significant decrease of low-density lipoprotein cholesterol. The mean serum triglyceride concentration did not change significantly. The fluctuations in the concentration of serum lipids and lipoproteins in 10 women not using oral contraceptives were smaller than in the women using oral contraceptives and no significant changes in the concentrations were found during one cycle. Thus, high-density lipoprotein cholesterol concentration decreases during each contraceptive cycle. The time of blood sampling during the cycle is, therefore, of vital importance in interpreting the effect of oral contraceptives on high-density lipoprotein cholesterol. In women not using oral contraceptives blood can be sampled on random days during the cycle.