Two studies in rhesus monkeys have shown that progesterone implants, Depo-Provera and Norplant, were associated with vaginal thinning. Progesterone implants have also been associated with an increased risk of simian immunodeficiency virus (SIV) acquisition. This study in 16 women was done to assess vaginal epithelial thickness and number of cell layers from biopsies taken in the untreated follicular and luteal phases, and at 1 month and 3 months after administration of Depo-Provera. There was no significant change over time in either parameter from biopsies obtained in the luteal phase compared with those at either time after Depo-Provera administration. There was also no change in the mean number of Langerhans cells in vaginal wall specimens and no change in cervical ectopy. It appears that women do not respond to exogenous progestins with the dramatic vaginal thinning seen in rhesus monkeys.

BACKGROUND

Ethiopia is the second most populous country in Africa with high fertility and fast population growth rate. It is also one of the countries with high maternal and child mortality rate in sub-Saharan Africa Family planning is a crucial strategy to halt the fast population growth, to reduce child mortality and improve maternal health (Millennium Development Goal 4 and 5). Therefore, this study aimed to assess the prevalence and determinants of modern contraceptive utilization among married women of reproductive age group.

METHODS

A community based cross-sectional study was conducted from August 15 to September 1, 2010 among married women aged 15-49 years in Debre Birhan District. Multistage sampling technique was used to select a total of 851 study participants. A pre-tested structured questionnaire was used for gathering data. Bivariate and multivariate logistic regression analyses were performed using SPSS version 16.0 statistical package.

RESULTS

Modern contraceptive prevalence rate among currently married women was 46.9%. Injectable contraceptives were the most frequently used methods (62.9%), followed by intrauterine device (16.8%), pills (14%), norplant (4.3%), male condom (1.2%) and female sterilization (0.8%). Multiple logistic regression model revealed that the need for more children (AOR 9.27, 95% CI 5.43-15.84), husband approve (AOR 2.82, 95% CI 1.67-4.80), couple's discussion about family planning issues (AOR 7.32, 95% CI 3.60-14.86). Similarly, monthly family income and number of living children were significantly associated with the use of modern contraceptives.

CONCLUSIONS

Modern contraceptive use was high in the district. Couple's discussion and husband approval of contraceptives use were significantly associated with the use of modern contraceptives. Therefore, district health office and concerned stakeholders should focus on couples to encourage communication and male involvement for family planning.

The objective of this study was to determine whether progestin-only contraceptives induce thinning of the vaginal epithelium in nonhuman primates. Eight intact rhesus monkeys (four per group) were treated with either a single intramuscular injection of 30 mg of Depo-Provera or a subcutaneous insertion of Norplant-II (2 x 75 mg rods; day 0). Norplant-II rods were removed 90 days after insertion. Vaginal biopsies were obtained during a pretreatment menstrual cycle and following treatment on days 10, 30, 60, 118, and 146. Formalin-fixed vaginal biopsies were evaluated for epithelial thickness and the degree of keratinization. The circulating levels of estradiol, progesterone, medroxyprogesterone acetate (MPA), or levonorgestrel (LNG) were monitored throughout the study by specific radioimmunoassays. Circulating levels of estradiol and progesterone confirmed the stage of the menstrual cycle in which pretreatment biopsies were obtained. Following treatment with Depo-Provera, serum levels of MPA increased to 2.3 +/- 0.6 ng/ml (x +/- SE, n = 4) within 24 hr. Serum levels of MPA were maximal on day 14 (5.5 +/- 0.9 ng/ml), dropped below 1 ng/ml by day 50, and were nondetectable by day 70. Circulating levels of LNG were elevated 24 hr after insertion of Norplant-II (5.8 +/- 3.0 ng/ml), peaked on day 2 (7.6 +/- 4.2 ng/ml), remained between 1.4 and 6.2 ng/ml from days 14 to 90, and were nondetectable by day 118, the first serum sample after removal of Norplant-II. There were no significant differences (p>> 0.05) in the epithelial thickness (microm), number of epithelial cell layers, or type of epithelium present in vaginal biopsies obtained during the follicular or luteal phases of the pretreatment menstrual cycle. Conversely, a pronounced effect of progestin treatment was observed on the vaginal epithelium. There were no significant differences (p>> 0.05) between the two progestin treatment groups, but a significant effect (p < 0.05) over time was observed (two-way ANOVA). Compared with pretreatment menstrual cycle controls, the vaginal epithelial thickness was decreased (p < 0.05) by day 30 or 60 following Norplant-II insertion or Depo-Provera injection, respectively. The number of epithelial cell layers was also decreased (p < 0.05) on days 30 and/or 60 in progestin-treated monkeys compared with pretreatment control cycles. Following removal of Norplant-II or metabolic excretion of MPA, the vaginal epithellium regenerated and the thickness was no longer different (p>> 0.05) from the pretreatment control cycle. These data demonstrate that progestin-only contraceptives induced thinning of the vaginal epithelium in rhesus monkeys, and this effect was rapidly reversible following physical or metabolic removal of the progestin.

OBJECTIVE

Since contraception is an effective way of preventing the vertical transmission of HIV, we evaluated the impact of a family planning intervention on hormonal contraceptive use and incident pregnancy in a group of HIV-positive and HIV-negative urban Rwandan women.

METHODS

In a longitudinal cohort study, 502 women who were not pregnant or infertile and who had been previously HIV tested and counseled viewed an informational video about hormonal contraception followed by a facilitated discussion. They were given access to oral or injectable hormonal contraception and Norplant at the research clinic; those who used these methods were seen every 3 months.

RESULTS

Of the 330 HIV-positive and 172 HIV-negative women who underwent the intervention, 120 either became new hormonal method users (n = 40), continued their previous use of a hormonal method (n = 64), or switched to another hormonal method (n = 16) following the intervention. There was a shift to use of longer lasting hormonal methods, and the annualized attrition rate was < 15%, compared to>> 50% prior to the intervention. Rates of oral and injectable contraceptive use were similar among HIV-positive and HIV-negative women. Nine per cent of HIV-positive women became pregnant in the year after the intervention compared to 22% in a prior 12 month period when contraceptives were not provided at the study site. The corresponding proportions for HIV-negative women were 20% after the intervention versus 30% before the intervention.

CONCLUSIONS

Access to and information about hormonal contraceptives resulted in increased use and reduced attrition among both HIV-positive and HIV-negative women in this study. The reduction in incident pregnancy was greatest among HIV-positive women, suggesting that factors other than access to hormonal contraceptives may have influenced fertility outcomes. Knowledge of HIV serostatus may have an important influence on family planning decisions.

BACKGROUND

This study examines contraceptive discontinuation due to method dissatisfaction among women in the United States.

METHODS

The study population, drawn from the 2002 National Survey of Family Growth, consisted of 6724 women (15-44 years of age) who had ever used a reversible contraceptive method. We first estimated the overall proportion of women who had ever discontinued their contraceptive due to dissatisfaction. We then calculated method-specific discontinuation risks due to dissatisfaction and analyzed the reasons for dissatisfaction given by women who had ever stopped using Norplant, Depo-Provera, oral contraceptives or condoms.

RESULTS

Overall, 46% of women had ever discontinued at least one method because they were unsatisfied with it. Dissatisfaction-related discontinuation risks varied widely by method: the diaphragm and cervical cap showed the highest proportions of such discontinuation (52%), followed by long-acting hormonal methods (42%). Oral contraceptives were associated with an intermediate risk of dissatisfaction-related discontinuation (29%), while condoms had the lowest risk (12%).

CONCLUSIONS

A broader understanding of women's concerns and experiences using contraception could help health care providers redesign counseling strategies to improve contraceptive continuation.

The United States-Mexico border is a region comprised of a country with one of the highest rates of invasive cervical cancer (Mexico) and a country with one of the lowest rates (United States). Recent evidence clearly indicates that human papillomavirus (HPV) infection is the cause of cervical cancer. The distribution of specific types of HPV is known to vary in different regions of the world, as do the cofactors that may inhibit or promote HPV carcinogenesis. Estimating the prevalence of oncogenic HPV is needed for guiding vaccine development. The purpose of this study was to determine the prevalence of oncogenic and nononcogenic HPV types and risk factors for HPV among women residing along the United States-Mexico border. A cross-sectional study of 2319 women, ages 15-79 years, self-referring for gynecological care was conducted between 1997 and 1998. HPV was detected by PCR using the PYGMY 09/11 L1 consensus primer, and HPV genotyping was conducted using the reverse line blot method. Overall, the HPV prevalence was 14.4% with no significant differences observed by country after adjustment for age. HPV 16 was the most commonly detected HPV type in both the United States and Mexico. Among women with high-grade squamous intraepithelial lesions, HPV types 58, 45, 51, 31, 35, 55, and 73 were most common in Mexico, and HPV types 18, 31, 35, 51, 52, and 58 were most common in the United States. In both countries, HPV prevalence declined linearly with age from 25% among women ages 15-19 years to 5.3% among women 56-65 years. Factors significantly independently associated with HPV infection were older age [adjusted odds ratio (AOR) = 0.15 for ages 56-65 years compared with those 15-19 years], a marital status other than married (AOR = 1.58-3.29), increased numbers of lifetime male partners (AOR = 3.8 for>> or =10 partners compared with 1 partner), concurrent infection with Chlamydia trachomatis (AOR = 1.79), ever use of Norplant (AOR = 2.69), and current use of injectable contraceptives (AOR = 2.29). Risk factors for HPV infection did not differ by country. Results from this study suggest that in addition to HPV 16 and 18, HPV types 31, 45, 51, and 58 should be considered for inclusion in an HPV prevention vaccine for distribution in Mexico.

OBJECTIVE

To examine bone density among adolescents receiving different forms of hormonal contraception along with that of control subjects.

METHODS

Baseline and 1-year measures of lumbar vertebral bone density were obtained in girls receiving depot medroxyprogesterone acetate (Depo-Provera) (n = 15), levonorgestrel (Norplant) (n = 7), or oral contraceptives (n = 9) and in girls receiving no hormonal treatment (n = 17). In a subsample of Depo-Provera users (n = 8), Norplant users (n = 3), and control subjects (n = 4), bone density measurements were repeated after 2 years. Bone density was measured by dual-energy x-ray absorptiometry.

RESULTS

Body mass indexes, level of pubertal development, substance use, and reproductive histories were not significantly different among the groups. More black girls were represented in the initial Depo-Provera group (p < 0.02), girls in the Norplant group exercised more hours per week (p < 0.02), and control subjects were older (p < 0.01) than those in the other groups. These variables did not significantly affect bone density results. After 1 year, bone density decreased 1.5% in Depo-Provera users, compared with increases of 2.5% in Norplant users, 1.5% in oral contraceptive users, and 2.9% control subjects (p < 0.02). After 2 years, bone density increased a total of 9.3% in Norplant users and 9.5% in control subjects but decreased a total of 3.1% in Depo-Provera users (p < 0.0001).

CONCLUSIONS

These data suggest that Depo-Provera may, at least temporarily, suppress the expected skeletal bone mineralization in adolescents, whereas Norplant and oral contraceptives are associated with the expected increase in bone density in this population.

BACKGROUND

Although levonorgestrel implants (Norplant) would appear to be a good contraceptive option for adolescent mothers, there is little information about the use of Norplant in this population.

METHODS

We studied 100 postpartum adolescents who chose a contraceptive method at an urban teaching hospital between September 1991 and July 1992. Structured interviews were conducted and medical records were reviewed soon after delivery and at a mean (+/- SD) of 15.5 +/- 2.9 months post partum.

RESULTS

Forty-eight of the adolescent mothers chose Norplant, 50 chose oral contraceptives, and 2 (not further studied) chose barrier methods of contraception. The factors significantly associated with the choice of Norplant were older age (16.7 years among those who chose Norplant, vs. 16.2 years among those who chose oral contraceptives), multiparity (24 subjects vs. 6 subjects), and previous use of oral contraceptives (34 subjects vs. 21 subjects). During follow-up, there were no differences between the Norplant group and the oral-contraceptive group in the frequency of clinic visits (an average of 2.3 visits per subject in each group), failure to return after the postpartum visit (9 subjects vs. 11 subjects), or the incidence of sexually transmitted diseases (42 percent vs. 36 percent). At follow-up, 95 percent of the subjects in the Norplant group and 33 percent of those in the oral-contraceptive group were still using the method they had chosen (P < 0.001). During the first postpartum year 1 subject in the Norplant group and 19 in the oral-contraceptive group became pregnant (P < 0.001). Norplant users did not differ from all other adolescents studied with regard to sexual activity or condom use.

CONCLUSIONS

The selection of Norplant by adolescent mothers as a method of contraception is associated with higher rates of continued use and lower rates of new pregnancy than the selection of oral contraceptives and does not affect the use of health care services, sexual activity, condom use, or the rate of sexually transmitted diseases.

BACKGROUND

Implantable methods of contraception offer long-acting reversible contraception. Their uptake rate in comparison to other contraceptive methods, particularly in developed countries, has historically been low.

OBJECTIVE

To assess the contraceptive effectiveness, tolerability and acceptability of subdermal implants in comparison to other reversible contraceptive methods.

METHODS

Literature were identified through database searches, reference lists and individuals/organisations working in the contraceptive field.

METHODS

All randomised and controlled trials comparing subdermal implants with other forms of reversible contraceptives and reporting on pre-determined outcomes in women of reproductive years. Primary outcomes were pregnancy and continuation.

METHODS

Quality assessment of studies and data extraction were completed independently by two reviewers. A quality checklist was designed to identify general methodological and contraceptive specific factors. Study authors and pharmaceutical companies were contacted to provide additional data.Data were collected on pregnancy rates, continuation, side effects and adverse events.

RESULTS

All nine identified trials compared different types of contraceptive implant. Eight, involving 1578 women, compared Implanon with Norplant , and one, involving 1198 women, compared Jadelle with Norplant. There was no difference between Implanon and Norplant for contraceptive effectiveness rates or continuation over 4 years. Both were highly effective methods of contraception with no pregnancies occurring in any of the trials during 26,972 and 28,108 women months of follow up respectively. The most common side-effect with Implanon and Norplant was changes in bleeding pattern. The pattern with Implanon was initially more variable, bleeding with both implants became less frequent with duration of use. After two years use the amenorrhoea rate was significantly higher with Implanon. The trials reported no significant difference in hormonal side-effects or adverse events. Implanon was significantly quicker to insert and remove than Norplant. There was no difference in contraceptive effectiveness and in continuation rates between Jadelle and Norplant. Jadelle was significantly quicker to remove than Norplant.

CONCLUSIONS

Implanon, Norplant and Jadelle are highly effective contraceptive methods. No significant differences were found in contraceptive effectiveness or continuation. The most common side-effect with all implants was unpredictable vaginal bleeding. Time taken for removal of Implanon and Jadelle was less than that for Norplant.Although this systematic review was unable to provide a definitive answer on relative effectiveness, tolerability and acceptability of contraceptive implants in comparison to other contraceptive methods, it has raised issues around the conduct of contraceptive research.

OBJECTIVE

To determine which components of a comprehensive, multidisciplinary, adolescent-oriented maternity program help teenage mothers delay subsequent pregnancies.

METHODS

A cohort of 373 participants in a comprehensive, multidisciplinary, adolescent-oriented maternity program was studied.

METHODS

The program was designed to prevent rapid subsequent pregnancies directly by simplifying access to contraceptives and indirectly by discouraging school drop-out and encouraging the pursuit of careers incompatible with closely spaced childbearing. Parents and children were seen together; nine visits were scheduled during the first postpartum year and four visits during the second year.

METHODS

Repeat adolescent pregnancy.

RESULTS

The repeat pregnancy rate was 14% at 1 year and 35% at 2 years. Teenage mothers who became pregnant exhibited significantly more repeat pregnancy risk factors but were as compliant with clinic visits as their nonpregnant peers. The contraceptive choices the teenagers made during the puerperium had the most profound effect on their subsequent fertility. A logistic regression analysis identified failure to use Norplant during the puerperium as the strongest predictor of repeat pregnancy during the first 2 postpartum years (relative risk [RR]=8.89; 95% confidence interval [CI]=2.80-28.50). Exhibiting nine or more repeat pregnancy risk factors (RR=2.37; 95% CI=1.38-4.06) and not using Depo-Provera during the puerperium (RR=2.30; 95% CI=1.60-3.29) also predicted repeat conception, but clinic visits and return to school postpartum did not.

CONCLUSIONS

Using a long-acting hormonal contraceptive during the puerperium was associated with pregnancy prevention during the first 2 postpartum years, but frequent clinic visits, contact with supportive healthcare and social service providers, and return to school were not.

OBJECTIVE

Levonorgestrel implants (Norplant) and medroxyprogesterone acetate injections (Depo-Provera) represent additional contraception options for adolescents. The purpose of this study was to examine prospectively clinical profiles among adolescents who chose one of the two long-term contraceptives compared with profiles among those who chose the combined oral contraceptive pill (OCP).

METHODS

Girls who needed contraception and did not require confidentiality were presented with a contraceptive menu consisting of Norplant (n = 58), Depo-Provera (n = 66), or OCP (n = 75). At baseline and follow-up visits over 6 months, patients were interviewed regarding gynecologic history, side effect symptoms, and satisfaction. The average age of subjects was 15.5 years (range 11 to 20 years); 66% were African-American and 34% white.

RESULTS

Significantly more teens who chose Depo-Provera (73%) reported having used some method of birth control previously than those selecting either Norplant (30%) or OCP (26%). Adolescents who chose either Norplant (34%) or Depo-Provera (43%) were significantly more likely to have been pregnant previously than those choosing OCP (12%). Those selecting Depo-Provera were significantly more likely to report a history of genital infection with Chlamydia trachomatis (42%) than those in the other two contraceptive groups (22%). Prevalences of reported recent depression and fatigue before initiation of treatment were high, exceeding 35% across the three groups. A total of 105 and 40 adolescents were assessed at 3 and 6 months, respectively. At follow-up, more than 80% of OCP users maintained regular menstrual cycles, whereas over 80% of those choosing Norplant or Depo-Provera had disrupted cycles. Complaints of nausea and dizziness among Norplant users and fatigue among Depo-Provera and OCP users increased significantly between the baseline and follow-up visits. Reports of local reactions to the Norplant device were common but not clinically significant. Blood pressure readings, facial acne, and body mass index did not change over time in any treatment group. Subjects in the Norplant and Depo-Provera groups appreciated freedom from daily compliance to maintain contraceptive effectiveness and the "hidden" nature of the method. Appointment compliance at the end of 6 months was 78% for Depo-Provera, 40% for Norplant, and 46% for OCP.

CONCLUSIONS

The implant and injection forms of contraception appear to be especially popular among girls with previous pregnancies or birth control use. The common occurrences of medical symptoms and sexually transmitted diseases before initiation of therapy underscore the importance of baseline evaluation. Norplant users may be warned about nausea and dizziness as well as minor local symptoms around the insertion site and unpredictable uterine bleeding patterns. Adolescent patients choosing Depo-Provera may expect amenorrhea by the end of 6 months of therapy along with possible fatigue. Early intervention may be needed with adolescents who choose Norplant or OCP to encourage better compliance with follow-up appointments.

OBJECTIVE

To review risk factors for rapid repeat pregnancy that have been studied among adolescents, and to determine which of these factors serve as useful predictors for second pregnancy.

METHODS

A Medline search of journal articles from 1966 to 1997 identified English language articles addressing repeat pregnancy among adolescents. All relevant citations within these articles were also included.

METHODS

Risk factors that were correlated with rapid repeat pregnancy in studies using rigorous statistical analysis were considered to be significant.

RESULTS

Significant predictors of rapid repeat pregnancy included younger age, low socioeconomic status, low education of teen's mother or head of household, marriage, intended or desired first pregnancy, and use of a contraceptive method other than Norplant postpartum.

CONCLUSIONS

There is little consensus as to which risk factors are the most important predictors of recidivism. With as many as half of teenage mothers conceiving again within two years, the identification of "high-risk" teens may be less important than the development of intervention strategies for all these young women.

BACKGROUND

The risk of HIV associated with hormonal contraceptives is controversial. We assessed hormonal contraceptive use and HIV incidence in HIV-discordant couples in Rakai, Uganda.

METHODS

HIV-discordant couples were retrospectively identified from a cohort between 1999 and 2009. Hormonal contraception included oral contraception, depomedroxyprogesterone acetate (DMPA), and implants (Norplant). Poisson regression estimated adjusted incidence rate ratios (adjIRRs) associated with hormonal contraceptive methods. A case-control subanalysis estimated odds ratios (ORs) of HIV associated with hormonal contraceptive, adjusted for viral load and age.

RESULTS

We identified 190 male HIV-positive/female HIV-negative (M+F-) and 159 male HIV- negative/female HIV-positive (M-F+) couples not using antiretroviral therapy or condoms. Female HIV incidence was 5.8/100 person-years (py) among nonhormonal contraceptive users, 12.0/100 py among oral contraceptive users [adjIRR 2.65, 95% confidence interval (CI) 0.82-8.60], 4.5 among Norplant users (adjIRR: 0.89, 95% CI 0.11-7.10), and 7.5/100 py among DMPA users (adjIRR 1.42, 95% CI 0.60-3.36). Male HIV incidence was 7.4/100 py during nonhormonal contraceptive use, 16.5/100 py during female oral contraceptive use (adjIRR 2.52, 95% CI 0.49-12.95), and 4.9/100 py with DMPA use (adjIRR 0.57, 95% CI 0.19-1.70). The number of female seroconverters was three among oral contraceptive users, one among Norplant users, and seven among DMPA users. Male seroconverters were two during female oral contraceptive use, none with Norplant use, and three with DMPA use. In a nested case-control analysis after adjustment for HIV viral load, the adjOR associated with oral contraceptive use was 1.59 (95% CI 0.32-97.85) for M+F- and 2.11 (95% CI 0.18-25.26) for M-F+ couples. For DMPA use, the adjOR was 1.44 (95% CI 0.46-4.51) for M+F- and 1.40 (95% CI 0.30-6.49) for M-F+ couples.

CONCLUSIONS

We did not observe significant risk of HIV acquisition or transmission with oral contraceptives or DMPA use in HIV discordant couples, but several point estimates were above 1.0 and statistical power was limited.

OBJECTIVE

The purpose of the present study was to examine condom use by teens who use hormonal contraceptives [i.e., Depo-Provera, Norplant, or oral contraceptives (OCs)].

METHODS

This is a cross-sectional study of 578 Hispanic and African-American female adolescents between the ages of 12 and 21 years who came to a reproductive health care clinic. A paper-and-pencil questionnaire which addressed sexual behaviors, sexual history, and communication about sexuality was distributed to adolescent girls attending the clinic. Several important analyses included only those who had been sexually active in the last 4 weeks (n = 452).

RESULTS

Adolescents who used OCs [odds ratio (OR) 1.7], long-acting agents (i.e., Depo-Provera or Norplant) (OR 1.6), were less likely to have used a condom in the last 4 weeks than teens whose only method of birth control was condoms. Only those teens who had previously been diagnosed with a sexually transmitted disease (STD) were more likely to have used a condom (OR .67 for not using a condom). Overall, condom use by teens in this sample was low, with only 19% reporting that they "always" use a condom, and 47% of the teens who had been sexually active in the last 4 weeks reporting that they had not used a condom at least once during that time.

CONCLUSIONS

This study provides data which suggest that adolescent girls who use hormonal contraceptives are less likely to use condoms than other sexually active teens. Therefore, when prescribing hormonal contraception to prevent pregnancy, clinicians must provide appropriate counseling to mitigate against the potential to increase the risk of STDs.

Recent studies demonstrate that combinations of androgens and progestagens are highly effective in the suppression of spermatogenesis in normal volunteers. To test whether progestagen and androgen delivery systems designed to produce steady serum levels will be as effective as other androgen plus progestagen combinations, we compared Norplant II and testosterone (T) transdermal patch to T patch alone on the suppression of spermatogenesis in normal men. Thirty-nine healthy male volunteers (age, 20-45 yr) were randomly assigned to one of two groups. Group 1 (n = 19) received two transdermal T patches daily (Testoderm TTS, each patch designed to deliver about 5 mg/d T) alone, and group 2 (n = 20) received combined Norplant II [Jadelle, four capsules delivering approximately 160 microg/d levonorgestrel (LNG)] plus T patch. Neither of these regimens were very effective, with suppression of spermatogenesis to severe oligozoospermia occurring in less than 60% of subjects. We then expanded the study to include two more groups to determine whether T patch or Norplant II was the main factor causing the inadequate suppression of spermatogenesis. Another 29 subjects were randomized to one of two groups. Group 3 (n = 15) received oral LNG (125 microg/d) plus T patch, and group 4 (n = 14) received Norplant II plus T enanthate (TE) injection (100 mg/wk i.m.). After a pretreatment phase of 4 wk, all subjects received treatment for 24 wk, followed by a recovery period of 12-24 wk. Steady-state serum LNG levels (800-1200 pmol/liter) were achieved from wk 3-24 after Norplant II insertion and decreased rapidly after the removal of the implants at wk 24. Trough serum LNG levels after oral LNG administration were at a comparable range (940-1300 pmol/liter). Azoospermia was achieved in 24%, 35%, 33%, and 93%, and severe oligozoospermia (<1 x 10(6)/ml) developed in 24%, 60%, 42%, and 100% of the subjects in groups 1, 2, 3, and 4, respectively, during treatment phase. All subjects in the Norplant II plus TE groups had persistent sperm concentrations less than 3 x 10(6)/ml from wk 12 until the end of treatment. Concomitant with the marked suppression of spermatogenesis in the Norplant II plus TE group, serum FSH and LH levels were most decreased in this group compared with all other groups. In the T patch-only group, serum SHBG was not suppressed, and total serum T was higher than baseline levels. In the other three groups administered progestagens, serum SHBGs were significantly suppressed, and serum total T remained similar to baseline levels. Serum free T levels were not changed in any group. Except for a suppression of serum high-density lipoprotein cholesterol, there was no significant change in weight, hematocrit, clinical chemistry, or prostate-specific antigen levels in any of the treatment groups. Although more efficacious than T patch alone, Norplant II or oral LNG plus T patch was not as effective in suppressing spermatogenesis to severe oligo- or azoospermia as in previous reports using oral LNG plus TE. This relative lesser efficacy occurred despite the achievement of serum LNG levels by Norplant II that were equivalent to those reported after administration of oral LNG. Substituting the transdermal T delivery system with TE injections resulted in very effective suppression of sperm output. The difference in spermatogenesis suppression of these combined regimens is likely due to less T delivered by the transdermal patch compared with the TE weekly injections. We conclude that Norplant II implants plus TE 100 mg/wk were very efficient in suppressing spermatogenesis to a level acceptable for contraceptive efficacy. This study demonstrates that the dose or route of administration of androgens is critical for sperm suppression in combined androgen-progestagen regimens for hormonal male contraception.

Levonorgestrel 6-capsule subdermal implants (Norplant) are an effective form of reversible contraception. When implanted under the skin of the upper arm, they release drug into the circulation at a relatively constant rate over 5 years. Generally, the cumulative pregnancy rate at the end of 5 years' levonorgestrel implant use is less than 2 per 100 users. The implants provide contraceptive efficacy equivalent to, or better than, that provided by other reversible methods (including oral contraceptives). Younger women are more likely than older women to become pregnant while using levonorgestrel implants. Bodyweight was positively correlated with risk of pregnancy in a number of studies, but may not be a factor with the currently available 6-capsule implant formulation. Limited data suggest that a new 2-rod levonorgestrel subdermal system (Jadelle) is as effective as the more extensively studied 6-capsule system and has a similar tolerability profile. Fertility returns rapidly after the implants are removed. Use of levonorgestrel subdermal implants is compatible with breast-feeding. In several studies, discontinuation rates were 2 to 15% during the first year of use; cumulative 5-year discontinuation rates ranged from 22 to 64 per 100 women. Despite a substantial incidence of adverse events during therapy, levels of user satisfaction are generally high. Menstrual abnormalities (increased or decreased menstrual flow, spotting, irregularity and amenorrhoea) affect most women at some time during therapy and are the most frequent reason for discontinuing levonorgestrel implants before the end of 5 years' treatment (incidence of 4.2 to 30.7 per 100 users). Mood changes and headache also may lead to discontinuation. Other reported adverse events include skin reactions (including acne), dizziness and weight gain. Serious adverse events (such as stroke, thrombotic thrombocytopenia and idiopathic intracranial hypertension) have been reported during levonorgestrel implants therapy, but the population incidence is difficult to calculate and causality is unclear. According to 3 pharmacoeconomic analyses from an institutional or managedcare perspective, all contraceptive interventions result in net cost savings. It is not clear whether levonorgestrel implants provide greater or smaller economic benefits than combined oral contraceptives.

CONCLUSIONS

Levonorgestrel subdermal implants provide effective long term contraception. Despite a high incidence of menstrual adverse events, overall levels of user satisfaction are high, and 1-year continuation rates are better than those for combined oral contraceptives. Levonorgestrel subdermal implants are a good choice of contraceptive method in women who desire effective contraception, but who are unable to, or prefer not to, comply with an oral regimen.

Many people in developing countries lack access to health technologies. We present seven findings about processes that shape access, based on analysis of six case histories: praziquantel to treat schistosomiasis (a parasitic worm disease), hepatitis B vaccine, the Norplant contraceptive, malaria rapid diagnostic tests, vaccine vial monitors, and the female condom. Each case study is assessed with a comprehensive framework that examines the effects of architecture, availability, affordability, and adoption on creating access. The analysis shows that access to health technology in poor countries is difficult to achieve because of multiple obstacles, but it can be created under certain conditions.

OBJECTIVE

To determine contraceptive use among HIV infected women attending Comprehensive Care Centre at Kenyatta National Hospital.

METHODS

Hospital based cross-sectional descriptive study.

METHODS

Comprehensive Care Centre (CCC), Kenyatta National Hospital.

METHODS

The study group was non-pregnant HIV positive women on follow up at the CCC. A total of 94 HIV infected women were interviewed between May 2006 and August 2006 through a pretested interviewer administered questionnaire. Consecutive women willing to participate in the study were interviewed.

METHODS

Current contraceptive use, contraceptive methods, source of contraception, reproductive intention and unmet need of family planning.

RESULTS

The mean age of the respondents was 34 years, 47.9% were married, all had formal education and 74.6% were employed. Eighty six percent of the respondents did not have reproduction intentions in the next two years; however, only 44.2% of the respondents were using contraception. Condoms were the most popular (81.5%) contraceptive method. Female condom was used by 10.5% of the respondents. Norplant was the only long-term contraceptive method and was used by only 2.6%. Dual method of contraception was practiced by 13.5% of the respondents. Majority of the respondents obtained contraceptives from private sector (42.9%) with less than 10% getting them from CCC. The unmet need for family planning among the study group was 30%. Marital status and regular sexual partner were significantly associated with contraceptive use.

CONCLUSIONS

Although majority of respondents did not have reproduction intentions in the next two years, use of contraception was low with only 44% being on a method. Use of long-term contraceptive methods was low among respondents. Majority of the respondents obtained contraceptives away from CCC. The unmet need for family planning was high at 30%.

Experience encompassing more than 20,000 woman-years of use of NORPLANT capsules and 6,000 woman-years of trials of NORPLANT-2 rods is reviewed. Implant contraception repeatedly has been associated with low pregnancy rates and high continuation rates through five full years of use. Weight has proved to be a factor related to effectiveness. Women weighing less than 50 kg experienced cumulative five-year pregnancy rates well below 1 per 100, whereas the overall cumulative rate has been 3.5 per 100. Medical events reported during use that have led to discontinuation are analyzed from four large data sets.

Expression of tissue factor (TF), the primary initiator of hemostasis via thrombin formation, is induced during progesterone (P4)-stimulated decidualization of human endometrial stromal cells (HESCs), and remains elevated in decidualized HESCs of luteal and gestational endometrium. In HESC monolayers, progestins elevate TF mRNA and protein levels and estradiol (E2) plus progestin further enhance TF levels for weeks despite no response to E2 alone. This in vitro model mimics the chronic differential ovarian steroid upregulation of TF levels associated with in vivo decidualization. After incubation of HESCs with E2 plus progestin to elevate TF expression, the antiprogestin RU486 completely reversed this upregulation. Thus, progesterone withdrawal transformed decidualization-associated hemostasis of the luteal phase endometrium to the hemorrhagic milieu of menstruation. Transient transfections with TF promoter constructs containing SP and EGR-1 binding sites before and after inactivation by site-directed mutagenesis revealed that Sp1 mediates basal and progestin-enhanced TF transcriptional activity. Progesterone receptor involvement in TF expression was further confirmed since RU486 was a pure antagonist of progestin-enhanced TF mRNA and protein expression, and progestin-enhanced, but not basal, Sp1-mediated transcriptional activity. Enhanced TF mRNA and protein levels in HESCs require co-incubation with progestin and epidermal growth factor receptor (EGFR) agonist indicating that the EGFR mediates progestin-enhanced TF expression. A peak in the primary angiogenic agent, vascular endothelial growth factor (VEGF) in luteal phase endometrium may be indirectly regulated by P4. Neither E2, nor progestin, nor E2 plus progestin affected VEGF expression in glandular epithelial and stromal cells, whereas thrombin enhanced VEGF mRNA and protein levels in decidualized HESCs, but not in the epithelial cells. Transudation of clotting factors to perivascular decidual cell TF in the luteal phase would generate thrombin, enabling it to act as an autocrine enhancer of VEGF in decidualized HESCs. Abnormal uterine bleeding complicates long-term progestin only contraceptive use. After Norplant administration, endometrial VEGF levels are elevated and TF levels are selectively enhanced in decidualized HESCs at bleeding sites. Over-expressed VEGF causes blood vessels to become leaky, increasing clotting factor access to decidualized HESC-expressed TF to promote feed-forward thrombin and VEGF formation. Since thrombin and VEGF induce angiogenesis via separate endothelial cell receptors, they may synergize to elicit aberrant angiogenesis, and ultimately lead to focal bleeding.

Abnormal uterine bleeding is the major reason for discontinuing long-term progesterone-only contraceptives (LTPOCs). Prior studies demonstrated that endometria exposed to the LTPOC, Norplant, display aberrant angiogenesis, leukocyte infiltration, and hypoxia-associated impaired blood flow. Paradoxically, human endometrial stromal cells (HESCs) of these specimens exhibit elevated expression of tissue factor (TF), the primary initiator of hemostasis via thrombin generation. The current study demonstrates that TF levels are also elevated in HESCs that are decidualized after insertion of Mirena, an intrauterine system that releases levonorgestrel directly into the endometrial canal and produces elevated perivascular levels of the proinflammatory and angiognenic cytokine IL-8. Because bleeding, inflammation, and ischemia-associated increased vascular permeability enhance access of plasma factor VII to HESC-expressed TF to generate thrombin, we evaluated the effects of steroids, thrombin, and hypoxia on HESC expression of IL-8. Confluent HESCs were incubated in a serum-containing medium for 7 d with vehicle control or estradiol (E(2)) plus medroxyprogesterone acetate (MPA). The medium was then exchanged for corresponding defined medium with and without thrombin, and the cultures were incubated in parallel for up to 48 h in a standard incubator (normoxia) or a sealed chamber at 0-1% O(2) (hypoxia). Under normoxia, immunoreactive IL-8 levels in the conditioned medium were reduced to one-third of control levels during decidualization with E(2)+MPA (P < 0.05; n = 5). In E(2)+MPA-treated cultures, thrombin (0.1 U/ml to 2.5 U/m) elicited a dose-dependent reversal of this inhibition, elevating IL-8 up to 60-fold (P < 0.05; n = 5) for more than 24 h and steady-state IL-8 mRNA levels by 3-fold for 3 h. The specific inactivator, hirudin, blocked most of the effects of thrombin, whereas TRAP-14, an agonist of the protease-activated receptor for thrombin, enhanced IL-8 output. In the absence of thrombin, hypoxia elevated IL-8 output 5-fold in E(2)+MPA-treated HESCs (P < 0.02, n = 4), with thrombin exerting additive effects. In contrast to its effects in progestin-treated HESCs, hypoxia did not elevate IL-8 output in control cultures. This study suggests that inhibition of IL-8 expression in decidualized HESCs contributes to the antiinflammatory milieu of the luteal phase. However, LTPOC-induced hypoxia and excess thrombin generation enhance IL-8 expression in decidualized HESCs, thereby eliciting aberrant angiogenesis and inflammation that promote the onset of abnormal uterine bleeding.

BACKGROUND

In the 1970s a new approach to the delivery of hormonal contraception was researched and developed. It was suggested that the addition of a progestogen to a non-medicated contraceptive device improved its contraceptive action. An advantage of these hormonally impregnated intrauterine systems (IUS) is that they are relatively maintenance free, with users having to consciously discontinue using them to become pregnant rather than taking a proactive daily decision to avoid conception.

OBJECTIVE

To assess the contraceptive efficacy, tolerability and acceptability of hormonally impregnated intrauterine systems (IUSs) in comparison to other reversible contraceptive methods.

METHODS

Literature was identified through database searches, reference lists and individuals/organisations working in the field. Searches covered the period from 1972 to November 2003.

METHODS

All randomised controlled trials comparing IUSs with other forms of reversible contraceptives and reporting on pre-determined outcomes in women of reproductive years. The primary outcomes were pregnancy due to method/user failure and continuation rate.

METHODS

The quality assessment of studies and data extraction were completed independently by two blinded reviewers. A quality checklist was designed to identify general methodological and contraceptive specific factors which could bias results. Events per women months and single decrement life table rates were extracted where possible for pregnancy, continuation, adverse events and reasons for discontinuation. Events per total number of women at follow up were collected for hormonal side effects and menstrual disturbance. When appropriate, data were pooled at the same points of follow up to calculate rate ratios in order to determine the relative effectiveness of one method compared to another. For the single decrement life table rates, the rate differences were pooled to determine the absolute difference in effectiveness of one method compared to another. Interventions were only combined if the contraceptive methods were similar. Non-hormonal IUDs were divided into three categories for the purpose of comparison with IUSs: IUDs >250mm2 (i.e. CuT 380A IUD and CuT 380 Ag IUD), IUDs <=250mm2 (i.e. Nova-T, Multiload, CuT 200 and CuT 220 IUDs) and non-medicated IUDs.

RESULTS

Twenty-one RCTs comparing hormonally impregnated IUSs to a reversible contraceptive method met the inclusion criteria and it was possible to include eight of these in the meta-analyses, four comparing LNG-20 IUSs with non-hormonal IUDs, one comparing the LNG-20 IUS with Norplant-2 and three comparing Progestasert with non-hormonal IUDs. No significant difference was observed between the pregnancy rates for the LNG-20 users and those for the IUD >250mm2 users. However, women using the LNG-20 IUS were significantly less likely to become pregnant than those using the IUD <=250mm2. Women using the LNG-20 IUS were more likely to experience amenorrhoea and device expulsion than women using IUDs >250mm2. LNG-20 users were significantly more likely than all the IUD users to discontinue because of hormonal side effects and menstrual disturbance, which on further breakdown of the data was due to amenorrhoea. When the LNG-20 IUS was compared to Norplant-2, the LNG-20 users were significantly more likely to experience amenorrhoea and oligomenorrhoea, but significantly less likely to experience prolonged bleeding and spotting. No other significant differences were observed. Progestasert users were significantly less likely to become pregnant and less likely to continue on the method than non-medicated IUD users after one year, but no significant difference was noted for these two outcomes when Progestasert users were compared to IUD<=250mm2 users. The only other significant differences found in the meta-analyses were that Progestasert users were less likely to expel the device and more likely to discontinue the method because of menstrual bleeding and pain than users of IUDs <=250mm2. REVIEWERS' CONCLUSIONl the device and more likely to discontinue the method because of menstrual bleeding and pain than users of IUDs <=250mm2.

CONCLUSIONS

Current evidence suggests LNG-20 IUS users are no more or less likely to have unwanted pregnancies than IUD >250mm2 and Norplant-2 users. The LNG-20 IUS was more effective in preventing either intrauterine or extrauterine pregnancies than IUDs <=250mm2. The contraceptive effectiveness of Progestasert was significantly better than non-medicated IUDs, but no difference was observed when compared to IUDs<=250mm2. Continuation of LNG-20 IUS use was similar to continuation of the non-hormonal IUDs and Norplant-2. Amenorrhoea was the main reason for the discontinuation for the LNG-20 IUS and women should be informed of this prior to starting this method.

To compare the contraceptive efficacy, tolerability, and bleeding patterns, 200 healthy female volunteers received, in an open, comparative, randomized, multicenter study in China, either a single-rod (Implanon) or a six-capsule (Norplant) contraceptive implant for 2 years with an optional extension of up to 4 years. Women were exposed to Implanon for 341.6 woman-years and Norplant for 329.1 woman-years. There were no pregnancies during the study. Per 90-day reference period, the median number of bleeding/spotting days with Implanon decreased from 33.5 in the first period to 19.0-21.5 days in the last year. Similarly, with Norplant, the median number of bleeding/spotting days decreased from 34.5 to 18.0-23.0 days, respectively. The number of bleeding/spotting episodes during year 1 was 2.0 per 90-day reference period with Implanon and 3.0 per period with Norplant (p < 0.05 for periods 1-4). For the remaining 90-day periods, there was no statistical difference between the two groups. In general, there was less frequent bleeding with Implanon compared with Norplant, whereas the incidences of amenorrhea and infrequent bleeding were higher with Implanon than with Norplant. The mean overall incidence of prolonged bleeding fell markedly during the study, from 66.0% in reference period 1 to 27.3% in period 16 with Implanon and from 69.0% to 21.7% with Norplant, respectively. The most common adverse events were related to disturbed bleeding patterns, which were also the major reasons for discontinuation (Implanon n = 8; Norplant n = 14). Normal menses returned in almost all subjects within 3 months after removal of the implants. Implanon was inserted in a mean time of 0.61 min and Norplant in 3.90 min (p < 0.001). Similarly, the mean time required to remove the implant was significantly shorter for Implanon than for Norplant (2.18 min vs 11.25 min, p < 0.001). The maximum time required for removal of the implant was 10 min for the Implanon group and 60 min for the Norplant group. In both groups, blood pressure and hemoglobin were not affected, whereas body weight tended to increase. It can be concluded that both contraceptive systems demonstrated excellent contraceptive efficacy and were well tolerated. Compared with Norplant, there was less frequent bleeding with Implanon, whereas the incidence of infrequent bleeding and amenorrhea was higher. Implanon was significantly quicker to insert and to remove than was the multiple capsule system.

OBJECTIVE

To study the mechanism of action of Implanon, a single-rod contraceptive implant containing etonogestrel, in healthy women during 3 years.

METHODS

Prospective, randomized comparison with Norplant. The study was conducted for 2 years in Sweden but was extended to 3 years in Finland.

METHODS

Two outpatient clinics.

METHODS

Thirty-two healthy women who were between 18 and 40 years of age with normal ovulatory cycles. Seven women receiving Implanon and three receiving Norplant participated in the third year.

METHODS

On or between days 1 and 5 of a spontaneous menstrual cycle, the subjects received either the etonogestrel-containing implant (Implanon) or the levonorgestrel-containing implant (Norplant).

METHODS

Ultrasonography was performed and/or progesterone concentrations were determined to confirm ovulation in a control cycle. Follicular development, endometrial thickness, and serum concentrations of 17beta-estradiol and progesterone were assessed twice per week during 4-week periods at regular intervals and after implant removal for 6 weeks to monitor return of ovulation. Times required to remove the respective implants were evaluated, as were possible complications.

RESULTS

Seven women who received Implanon and three who received Norplant completed 3 years of study. There were no pregnancies. Ovulation was observed for the first time with Norplant after 18 months. The first ovulation with Implanon was observed after 30 months. Mean endometrial thickness was <4 mm during treatment with Implanon from month 12 onward. The mean (+/-SD) time to remove Implanon was 5.9 +/- 3.4 minutes. The mean (+/-SD) time to remove Norplant was 17.9 +/- 9.9 minutes. Ovulation resumed promptly after the use of either implant.

CONCLUSIONS

Results from this study provide convincing evidence of 3-year contraceptive efficacy with Implanon, mainly by ovulation inhibition.