Contraceptive Efficacy Research Articles

Effect of efavirenz on levonorgestrel concentrations among Malawian levonorgestrel implant users for up to 30 months of concomitant use: a subanalysis of a randomized clinical trial

ObjectivesOur primary objective was to compare geometric mean levonorgestrel concentrations between levonorgestrel implant users who were or were not taking the antiretroviral efavirenz, for up to 30 months after implant initiation. Our secondary objective was to evaluate the pregnancy rate among levonorgestrel implant users on efavirenz. Study designWe performed a subanalysis of 42 Malawian women randomized to initiate the levonorgestrel implant as part of a parent randomized clinical trial. Our subset included 30 HIV-infected women taking efavirenz and 12 HIV-uninfected women not taking efavirenz. They underwent urine pregnancy testing every 3 months and serum levonorgestrel testing at day 3 and months 1, 3, 6, 12, 18, 24, 27 and 30 after implant initiation. Geometric mean levonorgestrel concentrations were calculated for efavirenz users and non-efavirenz users at each time point. ResultsThe geometric mean levonorgestrel concentrations were lower for efavirenz users than non-efavirenz users at every time point; the geometric mean ratio for efavirenz users:non-efavirenz users ranged from 0.60 [90% confidence interval (CI) 0.46–0.79] at 1 month to 0.27 (90% CI 0.12–0.61) at 30 months after implant insertion. No pregnancies occurred over 60 woman-years of concomitant levonorgestrel implant and efavirenz use, although 11 women had levonorgestrel concentrations <180 pg/mL (the previously suggested minimum threshold concentration for efficacy). ConclusionsEfavirenz users had lower levonorgestrel concentrations than non-efavirenz users, and one third of our concomitant efavirenz and levonorgestrel implant users had concentrations <180 pg/mL. Continued evaluation of the contraceptive efficacy of the levonorgestrel implant may be needed for efavirenz users. ImplicationsAmong 42 Malawian women using the levonorgestrel implant for contraception, women who were taking the antiretroviral efavirenz had lower serum levonorgestrel concentrations than women who were not taking efavirenz. However, none of the women who were taking efavirenz became pregnant over 60 women-years of follow-up.

Bleeding changes after levonorgestrel 52-mg intrauterine system insertion for contraception in women with self-reported heavy menstrual bleeding

The levonorgestrel 52-mg intrauterine system has proven efficacy for heavy menstrual bleeding treatment in clinical trials, but few data exist to demonstrate how rapidly the effects occur and the effects in women with self-reported heavy bleeding, as seen commonly in clinical practice. Evaluate changes in bleeding patterns in women with self-reported heavy menstrual bleeding before levonorgestrel 52-mg intrauterine system insertion. A total of 1714 women aged 16-45 years old received a levonorgestrel 52-mg intrauterine system in a multicenter trial evaluating contraceptive efficacy and safety for up to 10 years. At screening, participants described their baseline menstrual bleeding patterns for the previous 3 months. Participants completed daily diaries with subjective evaluation of bleeding information for the first 2 years. For this analysis, we included women with at least 1 complete 28-day cycle of intrauterine system use and excluded women using a hormonal or copper intrauterine contraception in the month prior to study enrollment. We evaluated changes in menstrual bleeding and discontinuation for bleeding complaints per 28-day cycle over 26 cycles (2 years) in women who self-reported their baseline pattern as heavy. We also compared rates of amenorrhea, defined as no bleeding or spotting, within the entire study population in women with subjective heavy menstrual bleeding at baseline compared with those who did not complain of heavy menstrual bleeding. Of the 1513 women in this analysis, 150 (9.9%) reported baseline heavy menstrual bleeding. The majority of women reported no longer experiencing heavy menstrual bleeding by the end of cycle 1 (112/150, 74.7%) with even greater rates by cycle 2 (124/148, 83.8%). At the end of cycles 6, 13, and 26, 129 of 140 (92.1%; 95% confidence interval, 87.7%-96.6%), 114 of 123 (92.7%; 95% confidence interval, 88.1%-97.3%), and 100 of 103 (97.1%; 95% confidence interval, 93.8%-100%) women reported no heavy menstrual bleeding, respectively. After cycles 13 and 26, 63 of 123 (51.2%; 95% confidence interval, 42.4%-60.1%) and 66 of 103 (64.1%; 95% confidence interval, 54.8%-73.3%), respectively, reported their bleeding as amenorrhea or spotting only. A lower proportion of women with baseline self-reported heavy menstrual bleeding reported amenorrhea as compared with women in the overall study cohort without heavy menstrual bleeding at the end of 6 cycles (319 [25.5%] vs 21 [15.0%], P=.005) and 13 cycles (382 [34.4%] vs 26 [21.1%], P=.003); differences were not significant after 19 cycles (367 [37.2%] vs 36 [31.0%], P=.022) and 26 cycles (383 [43.5%] vs 38 [36.9%], P=.21). Only 4 (2.7%) women with baseline heavy menstrual bleeding discontinued for bleeding complaints (2 for heavy menstrual bleeding and 2 for irregular bleeding), all within the first year. Most women who self-report heavy menstrual bleeding experience significant improvement quickly after levonorgestrel 52-mg intrauterine system insertion. Discontinuation for bleeding complaints among women with baseline heavy menstrual bleeding is very low.

Report of a Homeopathic Medication Regimen Containing Artemether/Lumefantrine in a Patient With Rheumatoid Arthritis.

Report of a Homeopathic Medication Regimen Containing Artemether/Lumefantrine in a Patient With Rheumatoid Arthritis.

The history of tiered-effectiveness contraceptive counseling and the importance of patient-centered family planning care

Public health workers, clinicians, and researchers have tried to increase long-acting reversible contraceptive (LARC) use by changing contraceptive counseling between patients and providers. Several major health organizations now recommend tiered-effectiveness counseling, in which the most effective methods are explained first so that patients can use information about the relative efficacy of contraceptive methods to make an informed choice. Some scholars and practitioners have raised concerns that, given histories of inequitable treatment and coercion in reproductive health care, tiered-effectiveness counseling may undermine patient autonomy and choice. This Clinical Opinion examines the development of tiered-effectiveness contraceptive counseling, how its rise mirrored the focus on promoting LARC to decrease the unintended pregnancy rate, and key considerations and the potential conflicts of a LARC-first model with patient-centered care. Finally, we discuss how reproductive justice and shared decision making can guide efforts to provide patient-centered contraceptive care.

Six-year contraceptive efficacy and continued safety of a levonorgestrel 52 mg intrauterine system

ObjectiveTo assess 6-year contraceptive efficacy and safety of a levonorgestrel 52 mg intrauterine system (IUS). Study DesignWe assessed pregnancy rates through 72 months in women aged 16–35 years at enrollment and safety in all participants (aged 16–45 years, n = 1751) in an ongoing 10-year phase-3 trial. ResultsOver six years, nine pregnancies occurred (none in year 6) for a life-table pregnancy rate of 0.87 (95% CI 0.44–1.70). Adverse event rates remain low through 6 or more years of use. Two expulsions occurred in year 6. ConclusionThis levonorgestrel 52 mg IUS is a highly effective and safe contraceptive over 6 years of use. ImplicationsThe levonorgestrel 52 mg IUS shows high 6-year contraceptive efficacy and a low rate of adverse events through 6 or more years of use.

First noncontrolled substance approved to treat narcolepsy in adults

In August, FDA approved pitolisant (Wakix—Harmony Biosciences) for treatment of excessive daytime sleepiness (EDS) in adult patients with narcolepsy. The selective histamine-3 receptor antagonist/inverse agonist is the first and only treatment for narcolepsy that is not scheduled as a controlled substance. “The approval of Wakix provides health care professionals managing people living with narcolepsy a new and important treatment option for their patients,” said Jeffrey Dayno, MD, Harmony Bioscience’s chief medical officer, in a statement. “Wakix … offers an important benefit/risk profile to address the unmet medical need that exists in people living with narcolepsy.” Pitolisant is available as both a 4.45-mg and 17.8-mg tablet and should be stored at 20°C to 25°C (68°F to 77°F). FDA’s approval was based on Harmony 1 and Harmony 1bis—two multicenter, double-blind, placebo-controlled studies. The studies randomized 261 patients to receive pitolisant, placebo, or active control. Participants were treated for 8 weeks, including a 3-week dose-titration phase followed by a 5-week stable-dose phase. In both studies, patients treated with pitolisant showed statistically significant improvement in EDS, as measured by the Epworth Sleepiness Scale. Common adverse effects of pitolisant include insomnia, nausea, and anxiety. The drug may also cause QT interval prolongation. Pitolisant may interact with a number of drugs. Its use with strong CYP2D6 inhibitors, for instance, increases the amount of pitolisant that patients are exposed to by 2.2-fold. The dose of pitolisant should be reduced by one-half, with a maximum dosage of 17.8 mg once daily, for patients who are concurrently using strong CYP2D6 inhibitors. Use of pitolisant with strong CYP3A4 inducers decreases the amount of pitolisant exposure in the blood by 50%. In patients taking CYP3A4 inducers, a dose adjustment should be considered, as detailed in pitolisant’s prescribing information. Pitolisant works by increasing the synthesis and release of histamine, so use of the drug with histamine-1 (H1) receptor antagonists that cross the blood–brain barrier may reduce its effectiveness. Patients taking pitolisant should avoid using centrally acting H1 receptor antagonists. Because pitolisant can prolong the QT interval, the drug should not be used in combination with other drugs that cause QT prolongation, as this can increase the risk of cardiac arrhythmia. Pitolisant may also reduce the effectiveness of sensitive CYP3A4 substrates, including hormonal contraceptives. Before they begin treatment with pitolisant, advise patients to inform their physician if they are taking, or planning to take, any prescription or OTC drugs. Counsel patients to consult their physician immediately if they feel faint, lose consciousness, or have heart palpitations, as these could be signs of prolongation of the QT interval. Pitolisant (Wakix)Manufacturer: Harmony BiosciencesDrug class: Histamine-3 (H3) receptor antagonist/inverse agonistIndication: Treatment of excessive daytime sleepiness (EDS) in adult patients with narcolepsyDosage: 17.8 mg to 35.6 mg once daily, taken orally in the morning upon awakening. Week 1: Start with 8.9 mg. Week 2: Increase dosage to 17.8 mg. Week 3: May increase to the maximum-recommended dosage of 35.6 mg. See prescribing information for more details.Of note: Pitolisant is contraindicated in patients with severe hepatic impairment (Child-Pugh C). The drug may increase the QT interval and could reduce the efficacy of hormonal contraceptives. Manufacturer: Harmony Biosciences Drug class: Histamine-3 (H3) receptor antagonist/inverse agonist Indication: Treatment of excessive daytime sleepiness (EDS) in adult patients with narcolepsy Dosage: 17.8 mg to 35.6 mg once daily, taken orally in the morning upon awakening. Week 1: Start with 8.9 mg. Week 2: Increase dosage to 17.8 mg. Week 3: May increase to the maximum-recommended dosage of 35.6 mg. See prescribing information for more details. Of note: Pitolisant is contraindicated in patients with severe hepatic impairment (Child-Pugh C). The drug may increase the QT interval and could reduce the efficacy of hormonal contraceptives. Pitolisant is metabolized extensively by the liver and is contraindicated in patients with severe hepatic impairment because the drug has not been studied in this population. Health care providers should monitor patients with moderate hepatic impairment, as these patients have shown increased amounts of the drug in their blood. Patients with mild hepatic impairment who are taking pitolisant should also be closely monitored. Emphasize to patients of reproductive potential that pitolisant may reduce the efficacy of hormonal contraceptives. Counsel these patients to use an alternative nonhormonal contraceptive method during treatment with pitolisant and for at least 21 days after discontinuing treatment. If a patient becomes pregnant during treatment with pitolisant, inform them that a pregnancy exposure registry is available to monitor pregnancy outcomes of the drug; patients can call 1-800-833-7460 to enroll or obtain information.

Evaluation of Sperm Impairing Factor from Serratia marcescens as Male Contraceptive in Mouse Model.

The present study was carried out to assess the contraceptive efficacy of sperm agglutinating factor (SAF) isolated from Serratia marcescens, in male Balb/c mice. Mice were administered via an intratesticular route with different concentrations of SAF, viz., 10, 50, 100, 200, or 400 µg, in the right testis only which served as a test while the left side served as control except otherwise stated. Mice were sacrificed on day 3, 7, 14, 21, 30, 45, 60, and 90 after administration, and results in terms of change in body weight, seminal parameters, tissue somatic indices (TSI), hematological parameters, serum level of testosterone, lipid peroxidation, and histology were studied. The body weight and TSI remained unaffected in all the experimental groups. In case of seminal parameters, the right testis treated with 10 μg, 50 μg, 100 μg, 200 μg, or 400 μg of SAF showed azoospermia up to day 7, 14, 21, 45, and 90, respectively. The hematological indices, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were found to be unaltered when the group receiving SAF (test) was compared with the groups receiving phosphate buffer saline (control) in the right testis; however, the treatment had a negative effect on the serum level of testosterone. It also affected the oxidative status of the right testis. Furthermore, histological studies revealed hypospermatogenesis and alterations in the seminiferous tubules which included intraepithelial vacuolation and exfoliation in the right side as compared to the left side. Thus, the results suggest that SAF (400 µg) causes suppression of spermatogenesis, without causing apparent toxic effects.

Contraceptive efficacy of sperm agglutinating factor from Staphylococcus warneri, isolated from the cervix of a woman with inexplicable infertility

BackgroundVoluntary control of fertility is of paramount importance to the modern society. But since the contraceptive methods available for women have their limitations such as urinary tract infections, allergies, cervical erosion and discomfort, a desperate need exists to develop safe methods. Vaginal contraceptives may be the answer to this problem, as these are the oldest ways of fertility regulation, practiced over the centuries. With minimal systemic involvement, these are also the safest. Natural substances blocking or impairing the sperm motility offer as valuable non-cytotoxic vaginal contraceptives. Antimicrobial peptides (AMPs) isolated from plants, animals and microorganisms are known to possess sperm immobilizing and spermicidal properties. Following this, in the quest for alternative means, we have cloned, over expressed and purified the recombinant sperm agglutinating factor (SAF) from Staphylococcus warneri, isolated from the cervix of a woman with unexplained infertility.MethodsGenomic library of Staphylococcus warneri was generated in Escherichia coli using pSMART vector and screened for sperm agglutinating factor (SAF). The insert in sperm agglutinating transformant was sequenced and was found to express ribonucleotide-diphosphate reductase-α sub unit. The ORF was sub-cloned in pET28a vector, expressed and purified. The effect of rSAF on motility, viability, morphology, Mg++-dependent ATPase activity and acrosome status of human sperms was analyzed in vitro and contraceptive efficacy was evaluated in vivo in female BALB/c mice.ResultsThe 80 kDa rSAF showed complete sperm agglutination, inhibited its Mg2+-ATPase activity, caused premature sperm acrosomal loss in vitro and mimicked the pattern in vivo showing 100% contraception in BALB/c mice resulting in prevention of pregnancy. The FITC labeled SAF was found to bind the entire surface of spermatozoa. Vaginal application and oral administration of rSAF to mice for 14 successive days did not demonstrate any significant change in vaginal cell morphology, organ weight and tissue histology of reproductive and non-reproductive organs and had no negative impact in the dermal and penile irritation tests.ConclusionThe Sperm Agglutinating Factor from Staphylococcus warneri, natural microflora of human cervix, showed extensive potential to be employed as a safe vaginal contraceptive.

Development of ReproKnow, a reproductive knowledge assessment for women with rheumatic diseases

BackgroundThe objective of this study was to develop an assessment tool, ReproKnow, to evaluate the reproductive health knowledge of women with a wide range of rheumatic diseases.MethodsThe 10-item multiple-choice questionnaire was developed with feedback from a panel of content experts and female patients with rheumatic diseases. Construct validity using known-groups analysis was evaluated through comparison of median total ReproKnow scores between rheumatology fellows and nurses. Female patients aged 18–50 years were recruited to take ReproKnow and demographic questionnaires in two outpatient clinics. Associations between patients’ mean total knowledge scores and demographic characteristics were assessed using independent-sample t-tests. Questions were also categorized by topical area, and the percentages were calculated.ResultsThe completion rate of questions in ReproKnow was 100% across all users. Median ReproKnow scores were significantly higher among rheumatology fellows than among nurses (p = 0.045). The 153 patients recruited to the study had at least one of 15 rheumatic diseases. Patients’ mean knowledge score was 5.05 (SD 2.24) out of a possible high score of 10. Patients who were younger, White, and more educated had significantly higher scores than did other patients (p’s < 0.05). Patients who bore children after their disease diagnosis had higher knowledge scores than did women whose children were born prior to their diagnosis; in contrast, women with histories of surgical sterilization or hysterectomy had lower knowledge scores than other women. Knowledge scores of women who used potentially fetotoxic medications did not vary from the remainder of the sample. Patients demonstrated gaps in knowledge about birth outcomes, contraceptive efficacy, and breastfeeding safety.ConclusionsInitial testing of ReproKnow suggests that it may be a promising tool to assess the reproductive health knowledge of women with diverse rheumatic diseases. Specific knowledge deficits elicited from ReproKnow may be important targets for future educational interventions.

Contraception and preconception counseling in women with autoimmune disease.

Appropriate contraception and preconception counseling are critical for women of reproductive age with systemic autoimmune diseases (AIDs) because clinical diagnosis, rheumatology medications, and disease activity may impact the safety or efficacy of certain contraceptives as well as the risk of adverse pregnancy outcomes. The presence of antiphospholipid (aPL) antibodies (anticardiolipin, anti-β2 glycoprotein I, and lupus anticoagulant) is the most important determinant of contraception choice, as women with these antibodies should not receive estrogen-containing contraceptives because of the increased risk of thrombosis. Prepregnancy counseling generally includes the assessment of preexisting disease-related organ damage, current disease activity, aPL antibodies, anti-Ro/SS-A and anti-La/SS-B antibodies, and medication safety in pregnancy. Quiescent AID for six months on pregnancy-compatible medications optimizes maternal and fetal/neonatal outcomes for most patients.

Comparison of self-reported female condom failure and biomarker-confirmed semen exposure

ObjectiveTo investigate whether rates of self-reported Woman's Condom (WC) clinical failure and semen exposure from a functionality study are comparable to results from a contraceptive efficacy substudy. Study designWe structured our comparative analysis to assess whether functionality studies might credibly supplant contraceptive efficacy studies when evaluating new female condom products. Couples not at risk of pregnancy in the functionality (breakage/slippage/invagination/penile misdirection) study and women in the contraceptive efficacy study completed condom self-reports and collected precoital and postcoital vaginal samples for up to four uses of the WC. Both studies used nearly identical self-report questions and the same self-sampling procedures and laboratory for prostatic specific antigen (PSA), a well-studied semen biomarker. We compared condom failure and semen exposure proportions using generalized estimating equations methods accounting for within-couple correlation. ResultsNinety-five (95) efficacy substudy participants used 334 WC and 408 functionality participants used 1572 WC. Based on self-report, 19.2% WC (64 condoms) clinically failed in the efficacy substudy compared to 12.3% WC (194 condoms) in the functionality study (p=.03). Of the 207 WC efficacy uses with evaluable postcoital PSA levels, 14.5% (30 uses) resulted in semen exposure compared to 14.2% (184 uses) of the 1293 evaluable WC functionality study uses. ConclusionsWhen evaluating the ability of an experimental condom to prevent semen exposure, the rate of clinical condom failure reported by participants risking pregnancy in an efficacy substudy was significantly higher than the rate reported by participants not risking pregnancy in a functionality study. The rate of semen exposure, assessed by an objective biomarker was nearly identical for the two studies. ImplicationsOur results suggest that an objective marker of semen exposure in functionality studies could provide a reasonable alternative to contraceptive efficacy studies in evaluating risk of unintended pregnancy and inferring protection from sexually transmitted infection than condom failure rates based on self-report.

A service evaluation of gait correction surgery for patients with hereditary spastic paraplegia

This process-improvement project improved postoperative education for female patients by facilitating the development of a topic-specific education program to improve knowledge and confidence among perianesthesia nurses in a military treatment facility.An educational program was developed and presented which reviewed the impact sugammadex has on steroidal contraceptive efficacy, evidence-based postoperative teaching strategies, and specific patient education recommendations for female sugammadex-exposed patients taking steroidal contraceptives.Effectiveness was measured by comparing nurses' baseline knowledge and confidence scores before and immediately after presentation of the educational program. These results were then compared with 2-week reassessments to determine if lasting improvements were achieved.Statistically significant increases in knowledge and confidence were achieved upon both postintervention assessments.Interactive evidence-based educational interventions can effectively create sustained increases in knowledge and confidence among health care professionals which translates into improved postoperative patient education.

Hormonal Contraceptives, Female Sexual Dysfunction, and Managing Strategies: A Review.

In recent decades, hormonal contraceptives (HC) has made a difference in the control of female fertility, taking an unequivocal role in improving contraceptive efficacy. Some side effects of hormonal treatments have been carefully studied. However, the influence of these drugs on female sexual functioning is not so clear, although variations in the plasma levels of sexual hormones could be associated with sexual dysfunction. Permanent hormonal modifications, during menopause or caused by some endocrine pathologies, could be directly related to sexual dysfunction in some cases but not in all of them. HC use seems to be responsible for a decrease of circulating androgen, estradiol, and progesterone levels, as well as for the inhibition of oxytocin functioning. Hormonal contraceptive use could alter women’s pair-bonding behavior, reduce neural response to the expectation of erotic stimuli, and increase sexual jealousy. There are contradictory results from different studies regarding the association between sexual dysfunction and hormonal contraceptives, so it could be firmly said that additional research is needed. When contraceptive-related female sexual dysfunction is suspected, the recommended therapy is the discontinuation of contraceptives with consideration of an alternative method, such as levonorgestrel-releasing intrauterine systems, copper intrauterine contraceptives, etonogestrel implants, the permanent sterilization of either partner (when future fertility is not desired), or a contraceptive ring.

Uterine bleedings and quality of woman's life

On March 12, 2019, an Advisory Board on impact of uterine bleedings on the quality of life of a woman was held in Kyiv, with participation of leading Ukrainian and European experts.According to opinion of international experts (guidelines of the UK National Institute for Health and Care Excellence and the International Federation of Gynecology and Obstetrics from 2018), the choice of patient management tactics is not determined by measuring blood loss, but by the patient’s well-being (distress, decrease of work ability, sexual activity and quality of life).Menstrual inflammation is phisiological and menstrual symptoms are usually mild/minor or absent when three criteria are fulfilled: resolving (normal cytoarchitecture of the tissue is reconstructed, endometrium first); limited in time; adequate and sufficient by intensity to finalize the reconstruction to the histological and functional characteristics of the different tissues involved. At the same time, if local and systemic inflammation associated with menstruation is excessive by intensity and duration, it can cause different pathological symptoms. Severe menstrual symptoms are clinically correlated with local and systemic inflammation, which is not resolving (menstruation is excessive in duration and intensity). Therefore, reducing menstrual inflammation is important to reduce the frequency and intensity of menstrual symptoms and improve the quality of life of women of reproductive age.Women need appropriate stable levels of estrogen and progesterone to optimize their physical and mental health. During combined oral contraceptives selection for healthy women it is reasonable to give preference to contraceptives with short hormonal free interval (24+4, 26+2) compared to the traditional regimen (21+7), since the reduction of this interval provides a more stable level of estradiol, reduces the risk of casual ovulation in case of missed pill, increases contraceptive efficacy in comparison with the traditional regimen and reduce the incidence of hormone-withdrawal associated symptoms.

Factors influencing young women's contraceptive choices.

Australia's high rate of unintended pregnancy could be lowered by increasing long-acting reversible contraception (LARC) use. Influences onAustralian women's choice of less effective methods are not well understood. This qualitative study explored factors that influence young women's contraceptive choices. Semi-structured interviews were conducted with women aged 18-24years until data saturation. Interviews were audio-recorded, transcribed and thematically analysed. Contraceptive choice was influenced by factors including contraceptive knowledge, side effects, cultural norms, fear, control and social context. Women often initiated contraceptive use for non contraceptive purposes such as management of acne or period pain, and failed to reconsider new methods when needing contraception, revealing one possible explanation for low LARC use. Findings indicate that women's contraceptive choices need regular review. Information about relative efficacy of contraceptive methods is necessary should women's reasons for using contraception include birth control in addition to non-contraceptive benefits.

A Pivotal, Multicenter, Non-Comparative Trial on the Contraceptive Efficacy, Safety, Tolerability of LPRI-424, 13 Cycles

A Pivotal, Multicenter, Non-Comparative Trial on the Contraceptive Efficacy, Safety, Tolerability of LPRI-424, 13 Cycles

Association of endogenous progesterone levels in young women using hormonal contraception with recent HIV-1 infection

BackgroundA high endogenous progesterone luteal state in the menstrual cycle has been independently associated with Human Immunodeficiency Virus (HIV) incidence in epidemiological studies. Hormonal contraception particularly high dose Depot Medroxyprogesterone Acetate (DMPA) is also thought to increase the risk of HIV acquisition. Inconsistent reports of this association have led us to hypothesize that unsuppressed endogenous progesterone level in women who reported hormonal contraception (HC) use may be an explanation for increased vulnerability to HIV.MethodsThis pilot study was a secondary cross-sectional analysis of data and laboratory testing of stored specimens collected from women who participated in the SAMRC HIV prevention MDP 301 trial during 2005–2009 in South Africa. Serum progesterone levels were measured in 39 women at the point of first positive HIV diagnosis during study follow-up and 36 women who remained HIV uninfected at the 52-week study exit visit.ResultsOverall, the median (IQR) progesterone level in 49 women using hormonal contraception was 0.39 ng/ml (IQR 0.13–0.45) and 48 (97.9%) women had a progesterone level < 3.0 ng/ml suggestive of adequate progesterone suppression for contraceptive efficacy. After excluding the one woman with a progesterone level of > 3.0 ng/ml, the median progesterone level in women using DMPA remained marginally higher at 0.42 ng/ml (IQR 0.27–0.45) than women using Norethisterone Enanthate (NET-EN) (0.31 ng/ml; IQR 0.13–0.41, p = 0.061). For women using hormonal contraception, the median progesterone level did not differ between women with recent HIV infection or women who remained HIV negative (0.39 vs 0.38 ng/ml, p = 0.959). Similarly, the median progesterone level in women using DMPA or NET-EN did not differ by HIV status (0.43 vs 0.41 ng/ml, p = 0.905; 0.24 vs 0.31 ng/ml, p = 0.889).ConclusionAmong women using hormonal contraception, DMPA or NET-EN we did not observe a significant difference in progesterone levels between women with recently acquired HIV infection and women who remained HIV negative. Our findings suggest that endogenous progesterone levels remain suppressed in the presence of hormonal contraception and are not likely to be associated with HIV acquisition.

OR33-5 Low Systemic Levels of Segesterone Acetate are Required to Inhibit Ovulation in Women

A one-year segesterone acetate (SA)/ethinyl estradiol (EE) contraceptive vaginal system (CVS; Annovera™) used to prevent pregnancy in women of reproductive age, was recently approved by the FDA (August 2018). Efficacy (Pearl Index of 2.98) and safety of the CVS were demonstrated in two phase 3, open-label, multicenter studies conducted in the US and internationally. The ring is self-inserted, left in place for 21 days and removed for 7 days in each cycle, and provides contraceptive efficacy for up to 13 cycles of use. It is designed to release 150 mcg SA and 13 mcg EE per day. This report reviews the evidence of systemic serum SA levels required for ovulation inhibition. SA is a potent synthetic progestin when given parenterally (eg, subcutaneous implant, transdermal gel, or vaginal ring), but, due to rapid inactivation by first-pass hepatic metabolism, is not biologically active when administered orally. SA specifically binds to progesterone receptors; it does not bind to sex hormone-binding globulin (SHBG) and has no estrogenic or androgenic activity. The effects of SA on ovulation inhibition were first examined in dose-finding studies of subdermal implants, which showed that the mechanism of ovulation inhibition was concentration dependent.1,2 Another study of subdermal implants releasing 45-50 mcg SA/day, showed ovulation did not occur with SA plasma levels >105 pmol/L; women who ovulated had SA levels ranging from 68 to <105 pmol/L.3 The effects of SA on ovulation inhibition were also evaluated in vaginal rings delivering 3 different doses (50, 75, 100 mcg/day) of SA for 6 months.4 These doses effectively inhibited ovulation, with SA serum levels remaining fairly constant through the study at ~125, 200 and 250 pmol/L, respectively, decreasing slightly over time.4 A study using a SA/estradiol transdermal gel demonstrated full suppression of ovulation and follicle growth at SA levels of 250 pmol/L.5 For better cycle control, EE was added to the vaginal ring for SA/EE (mcg/mcg per day) dosages of 50/10, 50/20, 150/15 (actual delivery 150/13), 150/20 and 200/15; ovulation inhibition was also evaluated in two trials with these doses.6,7 Overall, serum SA levels achieved with these rings were in the range of 200-300 pmol/L, well above levels required to inhibit ovulation.6,7 In both trials, body weight/BMI was inversely correlated with SA levels.6,7 The SA/EE CVS prevents ovulation when SA serum levels remain above 105 pmol. SA/EE CVS is novel, procedure-free and long-acting reversible contraceptive that can be used for up to one year. 1. Lahteenmaki PL, et al. Fertil Steril. 1985;44:20-24. 2. Haukkamaa M, et al. Contraception. 1992;45:49-55. 3. Diaz S, et al. Contraception. 1995;51:33-38. 4. Brache V, et al. Contraception. 2001;63:257-261. 5. Brache V, et al. Contraception. 2015;92:289-297. 6. Fraser IS, et al. Contraception. 2005;72:40-45. 7. Sivin I, et al. Contraception. 2005;71:122-129.

Perceived infertility and contraceptive use in the female, reproductive-age cancer survivor

To estimate the association between perceived fertility potential and contraception use and to characterize factors important in contraceptive decision making in reproductive-age, female cancer survivors. Cross-sectional study. Participants were from two state cancer registries, physician referrals, and cancer survivor advocacy groups in the United States. A total of 483 female survivors aged 18-40years. Online questionnaire. Contraception use. Eighty-four percent of participants used contraception; 49.7% used highly effective, World Health Organization tiers I and II methods (surgical sterilization, intrauterine devices, contraceptive implant, combined hormonal contraceptives, medroxyprogesterone acetate, progestin-only pills, contraceptive diaphragm). Contraception non-use was more common among survivors who perceived themselves to be infertile, compared with survivors who perceived themselves to be as or more fertile than similarly aged peers (prevalence ratio 4.0, 95% confidence interval 2.5-7.4). In mediation analysis that adjusted for clinical infertility, 59% of the association between prior chemotherapy and contraception non-use was explained by perceived infertility. Contraception efficacy (n = 62, 25.8%) and ease of use (n = 50, 20.8%) were the most cited reasons for using tier I/II methods; compared with lack of hormones (n = 81, 49.7%) as the predominant reason for using less-effective, tier III/IV methods. Although female, reproductive-age cancer survivors had high uptake of contraception, those who perceived themselves to be infertile were less likely to use contraception. Throughout survivorship, clinicians should counsel survivors on fertility potential in the context of their prior cancer treatments and on factors, including contraceptive efficacy and hormone-free contraception, that inform reproductive decision making in this population.

Contraceptive Efficacy a Retrospective Analysis Among Nigeriant

Contraception is one of reproductive health’s essential elements. It enables young people to determine the timing and number of their children and empowers them with respect and dignity to manage their live