Contraceptive Ring Research Articles

Are the Effects of Oral and Vaginal Contraceptives on Bone Formation in Young Women Mediated via the Growth Hormone-IGF-I Axis?

Purpose: Combined hormonal contraceptive therapy has been associated with negative bone mineral density outcomes that may be route-dependent [i.e., combined oral contraception (COC) vs. contraceptive vaginal ring (CVR)] and involve the hepatic growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis. The objective of the pilot study was to assess the impact of route of contraceptive administration on IGF-I and procollagen type I N-terminal propeptide (PINP) responses to an IGF-I Generation Test. We hypothesized that the peak rise in IGF-I and PINP concentration and area under the curve (AUC) would be attenuated following COC, but not CVR, use.Methods: Healthy, premenopausal women not taking hormonal contraception were recruited. Women were enrolled in the control group (n = 8) or randomly assigned to COC (n = 8) or CVR (n = 8) for two contraceptive cycles. IGF-I Generation Tests were used as a probe to stimulate IGF-I release and were completed during the pre-intervention and intervention phases. Serum IGF-I and PINP were measured during both IGF-I Generation Tests. The study was registered at ClinicalTrials.gov (NCT02367833).Results: Compared to the pre-intervention phase, peak IGF-I concentration in response to the IGF-I Generation Test in the intervention phase was suppressed in the COC group (p < 0.001), but not the CVR or Control groups (p > 0.090). Additionally, compared to the pre-intervention phase, PINP AUC during the intervention phase was suppressed in both COC and CVR groups (p < 0.001), while no difference was observed in the control group (p = 0.980).Conclusion: These data suggest that changes in recombinant human GH-stimulated hepatic IGF-I synthesis in response to combined hormonal contraception (CHC) use are dependent on route of CHC administration, while the influence on PINP is route-independent. Future research is needed to expand these results with larger randomized control trials in all age ranges of women who utilize hormonal contraception.Clinical Trial Registration: www.ClinicalTrials.gov registration NCT02367833.

Metformin metabolic and vascular effects in normal weight hyperinsulinemic polycystic ovary syndrome patients treated with contraceptive vaginal ring. A pilot study

Purpose The aim of this longitudinal, controlled, and retrospective pilot study was to assess how metformin, associated with a contraceptive vaginal ring, may influence lipid and carbohydrate metabolism, and surrogate markers of arterial function in normal weight polycystic ovary syndrome patients. Material and Methods Among 28 lean patients, 15 were treated with vaginal ring plus metformin and 13 women with only vaginal ring. The effects were assessed after six months. The patients were submitted to evaluation of lipid and carbohydrate metabolism; Doppler analysis of ophthalmic artery; brachial artery flow-mediated vasodilatation; and oral glucose tolerance test. Results After six months, the fasting insulin, glucose/insulin ratio, and homeostatic model assessment estimates for insulin resistance were significantly improved in metformin group. The ophthalmic artery pulsatility index did not significantly improve in either group. The brachial artery vasodilation was better in metformin treated patients. Conclusion Metformin, associated with vaginal ring, improves the insulin and carbohydrate metabolism. This, associated with the significant improvements of surrogate markers of arterial function, may be responsible of a slight possible cardiovascular and cerebrovascular protective effect.

Dose-finding study of a 90-day contraceptive vaginal ring releasing estradiol and segesterone acetate

ObjectiveTo evaluate serum estradiol (E2) concentrations during use of 90-day contraceptive vaginal rings releasing E2 75, 100, or 200 mcg/day and segesterone acetate (SA) 200 mcg/day to identify a dose that avoids hypoestrogenism. Study designWe conducted a multicenter dose-finding study in healthy, reproductive-aged women with regular cycles with sequential enrollment to increasing E2 dose groups. We evaluated serum E2 concentrations twice weekly for the primary outcome of median E2 concentrations throughout initial 30-day use (target ≥40 pg/mL). In an optional 2-cycle extension substudy, we randomized participants to 2- or 4-day ring-free intervals per 30-day cycle to evaluate bleeding and spotting based on daily diary information. ResultsSixty-five participants enrolled in E2 75 (n = 22), 100 (n = 21), and 200 (n = 22) mcg/day groups; 35 participated in the substudy. Median serum E2 concentrations in 75 and 100 mcg/day groups were <40 pg/mL. In the 200 mcg/day group, median E2 concentrations peaked on days 4–5 of CVR use at 194 pg/mL (range 114–312 pg/mL) and remained >40 pg/mL throughout 30 days; E2 concentrations were 37 pg/mL (range 28–62 pg/mL) on days 88–90 (n = 11). Among the E2 200 mcg/day substudy participants, all had withdrawal bleeding following ring removal. The 2-day ring-free interval group reported zero median unscheduled bleeding and two (range 0–16) and three (range 0–19) unscheduled spotting days in extension cycles 1 and 2, respectively. The 4-day ring-free interval group reported zero median unscheduled bleeding or spotting days. ConclusionsEstradiol concentrations with rings releasing E2 200 mcg/day and SA 200 mcg/day avoid hypoestrogenism over 30-day use. ImplicationsA 90-day contraceptive vaginal ring releasing estradiol 200 mcg/day and segesterone acetate 200 mcg/day achieves estradiol concentrations that should avoid hypoestrogenism and effectively suppresses ovulation.

A technology evaluation of Annovera: a segesterone acetate and ethinyl estradiol vaginal ring used to prevent pregnancy for up to one year

ABSTRACT Introduction The segesterone acetate and ethinyl estradiol contraceptive vaginal ring (SA/EE CVR) was FDA-approved in August 2018 and is now available in the U.S. The CVR is placed vaginally for 21 days followed by a 7-day ring-free interval, when withdrawal bleeding typically occurs. One ring can be used for up to a year (13 cycles). Areas covered This review summarizes this novel method of contraception, including the delivery system and the hormonal components. We describe the potential market, how it is used, the pharmacokinetic properties of the device, and results of clinical trials including efficacy, bleeding profile, acceptability, and safety. Expert opinion The SA/EE CVR represents the first long-lasting user-controlled hormonal contraceptive device. The bleeding pattern is highly favorable and consistent over the entire year and is associated with very low discontinuation. Efficacy and safety are similar to other methods of combined hormonal contraceptives. Unscheduled ring removals increase the risk of failure. Further studies are needed to evaluate continuous use of the ring for greater than 21 days, and potential non-contraceptive benefits of the ring such as reduced menstrual bleeding.

Elution from intact and broken vaginal contraceptive rings: an in vitro study.

The in vitro elution of the active substances etonogestrel (ETO) and ethinylestradiol (EE) of Ornibel® (a vaginal delivery system) was determined after a deliberate breakage of the vaginal contraceptive ring and compared to the standard elution and hormone release of intact rings under the same experimental conditions. Ornibel® intact and broken vaginal rings were placed in a dissolution buffer and subject to a repetitive sampling of ETO and EE following a standardized in vitro elution (IVE) procedure for 21 days. The hormone dissolution profile was determined by HPLC using a fully validated analytical method. In a second study, rings were broken after day seven, and their elution profiles were compared to that of intact rings. For all utilized batches, the stability conditions established were 24 months at 5°C. Furthermore, no special storage conditions are needed. The instantaneous elution on day 1 of ETO and EE for intact rings were 119±8 µg/day and 15±1 µg/day, respectively (mean ± SD), which was non-significantly different to the immediate release of ETO and EE for broken rings (118±4 µg/day and 14±1 µg/day). The average elution profile for days 2-20 were 132±5 µg/day and 18±1 µg/day (ETO/EE, intact rings) and 132±4 µg/day and 19±1 µg/day (ETO/EE, broken rings) respectively. On day 21, the elution of ETO and EE was numerically similar 111±5 (±4) µg/day and 18±1 µg/day) for both intact and broken rings. The IVE results from intact rings and vaginal rings deliberately cut on day seven similarly did not differ in their release of ETO and EE. Our study concludes that the hormonal release of ETO and EE from Ornibel® are similar for intact and broken vaginal rings under standardized in vitro conditions.

Gynecologic Management of Adolescents and Young Women With Seizure Disorders: ACOG Committee Opinion, Number 806.

Seizure disorders frequently are diagnosed and managed during adolescence; therefore, obstetrician-gynecologists who care for adolescents should be familiar with epilepsy and other seizure disorders, as well as antiepileptic drugs. Patients diagnosed with seizure disorders during childhood may have increased seizure activity with puberty and menarche due to the neuroactive properties of endogenous steroid hormones. Compared with patients without epilepsy, patients with epilepsy are more likely to experience anovulatory cycles, irregular menstrual bleeding, and amenorrhea. Although hormonal suppression should not be initiated before puberty or menarche, prepubertal counseling may be appropriate, and obstetrician-gynecologists may work with young patients and their families to develop a plan to initiate with menarche. Additionally, obstetrician-gynecologists should be aware of any medication changes, including antiepileptics, for adolescent patients with seizure disorders. Research on hormonal therapy for the treatment of epilepsy is scant; however, the anticonvulsant properties of various progestins have been explored as potential treatment. There is no conclusive evidence that combination hormonal contraception increases epileptic seizures, and epilepsy itself poses no increased risk of an adverse outcome for those using combined oral contraceptive pills, the contraceptive patch, or a contraceptive ring. Because many antiepileptic drugs are teratogenic, discussing sexual health with and providing effective contraceptive choices to this population is critical. Obstetrician-gynecologists should work with patients with seizure disorders to develop a plan when pregnancy occurs.

Gynecologic Management of Adolescents and Young Women With Seizure Disorders: ACOG Committee Opinion Summary, Number 806.

Seizure disorders frequently are diagnosed and managed during adolescence; therefore, obstetrician-gynecologists who care for adolescents should be familiar with epilepsy and other seizure disorders, as well as antiepileptic drugs. Patients diagnosed with seizure disorders during childhood may have increased seizure activity with puberty and menarche due to the neuroactive properties of endogenous steroid hormones. Compared with patients without epilepsy, patients with epilepsy are more likely to experience anovulatory cycles, irregular menstrual bleeding, and amenorrhea. Although hormonal suppression should not be initiated before puberty or menarche, prepubertal counseling may be appropriate, and obstetrician-gynecologists may work with young patients and their families to develop a plan to initiate with menarche. Additionally, obstetrician-gynecologists should be aware of any medication changes, including antiepileptics, for adolescent patients with seizure disorders. Research on hormonal therapy for the treatment of epilepsy is scant; however, the anticonvulsant properties of various progestins have been explored as potential treatment. There is no conclusive evidence that combination hormonal contraception increases epileptic seizures, and epilepsy itself poses no increased risk of an adverse outcome for those using combined oral contraceptive pills, the contraceptive patch, or a contraceptive ring. Because many antiepileptic drugs are teratogenic, discussing sexual health with and providing effective contraceptive choices to this population is critical. Obstetrician-gynecologists should work with patients with seizure disorders to develop a plan when pregnancy occurs.

In Memoriam: C. Wayne Bardin, MD (1934 - 2019).

It is with great sadness that we announce that C. Wayne Bardin, MD passed away peacefully on October 10, 2019 at his home in New York City, his wife Beatrice at his side. This was not unexpected, as he had been in declining health for several years, but his death nonetheless marks the loss of a true giant in the field of Endocrinology. Wayne was known not only for his intellect, creativeness, teaching, mentorship, and scientific leadership worldwide but also for his love of family, friends, and humanity. He is survived by his wife Beatrice, two daughters Stephanie Torre (Tony) and Charlotte Merritt (Michael), stepchildren, and grandchildren. Dr. Bardin was born in West Texas in 1934. He graduated from Rice University in 1957, matriculated to Baylor College of Medicine, pursued his medical residency at Cornell University, New York Hospital and then did his endocrine fellowship at the National Cancer Institute in 1962 under the mentorship of Drs. Mortimer Lipsett and Griff Ross. He remained at the NIH as a senior investigator until becoming Professor and Chief, Division of Endocrinology at the Pennsylvania State University College of Medicine, Hershey, in 1970. After eight years, Wayne joined the Population Council, at Rockefeller University, as Director of the Center for Biomedical Research and Vice President of the Population Council. Although he retired from the Population Council in 1996, he remained active as a private consultant to biomedical corporations seeking his expertise and advice regarding potential contraceptive products requiring FDA approval. Wayne Bardin’s research accomplishments are both numerous and legendary. On the eve of being able to measure hormone levels in small quantities of blood, he began his studies of the feedback regulation of pituitary hormones while at Baylor and his prescient studies of steroid metabolism during his medical residency at Cornell under the tutelage of Dr. Ralph Peterson. During his NIH tenure, he focused on animal models of androgen resistance and androgen regulation of cellular proliferation. Subsequently, however, his clinical research took a major turn to encompass studies of methods to regulate reproductive function in men and women, and pioneering effective and affordable contraceptive trials worldwide; particularly among impoverished populations. Most notably, he developed a subdermal implant (Norplant) that would provide effective reversible contraception for women up to five years. Additionally, he evaluated intra-uterine devices (copperT-200 and T-380), the effectiveness of RU-486 for medical termination of pregnancy, and synthesis and trials of Nestorone in various formulations including as a contraceptive vaginal ring. Wayne was prolific in his scientific reports publishing over 500 papers and book chapters. His teaching and mentorship included about 120 individuals worldwide who trained under him; many of whom have gone on in their own right to become senior investigators, thought leaders, department chairs, and award honorees. Dr. Bardin’s leadership role was exemplary. Within andrology, he was active in the National Prostate Cancer Task Force, NCI (1973-78), Council member and President of our American Society of Andrology (1988-89). Within the general endocrine community, he was Director of the Clinical Endocrinology Update course for many years; and member of the Endocrine Society Council before becoming its President (1993-94) and Chairman, of the International Committee for Contraception Research of the Population Council from 1978-96. His consultative endeavors and responsibilities included numerous NIH research grant study sections, journal editorial boards, and international committees too long to list. Dr. Bardin received numerous awards including Distinguished Andrologist (1984 and 1992), membership in the Institute of Medicine, awardee of Doctor Honoris Causa at the University of Caen, France; the University of Pierre and Marie Curie, Paris, France; and the University of Helsinki, Finland; and Commander of the Order of the Lion of Finland among others. Wayne was not all about science. He had an insatiable appetite for the arts and music and theater. He did not hesitate, at a later age, to learn how to ski with the encouragement of his wife Beatrice. Those of us who trained under Dr. Bardin deeply mourn his death. He was our mentor, inspiration, colleague, and friend. He gave generously of his personal time to enhance our own career success. We have all tried to emulate his style; but none can match his unique greatness.

Surface roughness of different contraceptive vaginal rings: evaluation by scanning electron microscope (SEM)

Objective: The aim of the study was to evaluate whether the compositions of the ethylene vinyl acetate (EVA) membrane of two different contraceptive vaginal rings could influence the surface roughness, which is associated with the possible accumulation of vaginal biomass on the rings during use.Methods: We measured and compared the surface roughness of unused vaginal rings, NuvaRing and Ornibel, using a scanning electron microscope (SEM) and dedicated software that can convert SEM images into 3D models. Average roughness (Ra), average quadratic roughness (Rq) and mean height of the irregularities at 10 points (Rz) were calculated.Results: Different thicknesses of the EVA membranes between the two rings were noted. No significant differences were found between the two rings in the three evaluated values of surface roughness (NuvaRing vs Ornibel, respectively: Ra, 1.53 ± 0.14 vs 1.61 ± 0.14 µm, p = 0.141; Rq, 2.03 ± 0.25 vs 2.07 ± 0.16 µm, p = 0.688; Rz, 11.4 ± 3.1 vs 11.4 ± 2.4 µm, p = 0.987).Conclusion: The different composition of the vaginal rings’ EVA membrane is not associated with different surface roughness. Ornibel is equivalent to NuvaRing in terms of surface roughness, despite the different composition of the membrane polymers.

Ovarian reserve markers in women using various hormonal contraceptives

Objectives: The aim of the study was to assess whether the ovarian reserve markers anti-Müllerian hormone (AMH) and antral follicle count (AFC) were lower among women using the progestin-only pill (POP) or levonorgestrel-releasing intrauterine system (LNG-IUS) and similar to the decrease observed in combined oral contraceptive (COC) pill users.Methods: This retrospective study comprised 565 hormonal contraceptive users (COC, POP, LNG-IUS or contraceptive vaginal ring) and 983 non-hormonal contraceptive users, who were seen in two Danish fertility assessment and counselling clinics between 2015 and 2019. Adjusted multiple regression analysis was used to examine the differences in AMH and AFC between hormonal and non-hormonal contraceptive users.Results: Compared with non-hormonal contraceptive users, AMH was 31.1% lower among COC users [95% confidence interval (CI) −39.6%, −25.9%; p < 0.001], 35.6% lower among POP users (95% CI −49.0%, −18.6%; p < 0.001) and 17.1% lower among LNG-IUS users (95% CI −31.4%, 0.002%; p = 0.052); no significant differences were seen among vaginal ring users. Compared with non-hormonal contraceptive users, AFC was 31.3% lower among COC users (95% CI −35.0%, −25.3%; p < 0.001) and 29.7% lower among POP users (−39.1%, −17.9%; p < 0.001); no significant differences were seen among LNG-IUS or vaginal ring users. Ovarian volume was more than 50% reduced among COC and vaginal ring users (p < 0.001) but was unchanged among POP and LNG-IUS users.Conclusion: Assessment of ovarian reserve markers among users of all types of hormonal contraception should be interpreted cautiously and the type of contraceptive method considered.

Emergency Contraception.

Despite significant declines over the past 2 decades, the United States continues to experience birth rates among teenagers that are significantly higher than other high-income nations. Use of emergency contraception (EC) within 120 hours after unprotected or underprotected intercourse can reduce the risk of pregnancy. Emergency contraceptive methods include oral medications labeled and dedicated for use as EC by the US Food and Drug Administration (ulipristal and levonorgestrel), the "off-label" use of combined oral contraceptives, and insertion of a copper intrauterine device. Indications for the use of EC include intercourse without use of contraception; condom breakage or slippage; missed or late doses of contraceptives, including the oral contraceptive pill, contraceptive patch, contraceptive ring, and injectable contraception; vomiting after use of oral contraceptives; and sexual assault. Our aim in this updated policy statement is to (1) educate pediatricians and other physicians on available emergency contraceptive methods; (2) provide current data on the safety, efficacy, and use of EC in teenagers; and (3) encourage routine counseling and advance EC prescription as 1 public health strategy to reduce teenaged pregnancy.

Impact of Hormonal Contraceptives on Cervical T-helper 17 Phenotype and Function in Adolescents: Results from a Randomized, Crossover Study Comparing Long-acting Injectable Norethisterone Oenanthate (NET-EN), Combined Oral Contraceptive Pills, and Combined Contraceptive Vaginal Rings.

BackgroundAdolescents in sub-Saharan Africa are at risk for human immunodeficiency virus (HIV) infection and unintended pregnancies. Observational studies suggest that injectable hormonal contraceptives (HCs) increase the HIV risk, although their effects on genital inflammation, particularly HIV-susceptible T-helper 17 (Th17) cells, are unknown. In a randomized crossover study, the effect of injectable norethisterone oenanthate (NET-EN), combined contraceptive vaginal rings (CCVR; NuvaRing), and combined oral contraceptive pills (COCPs) on cervical Th17 cells and cytokines were compared.MethodsAdolescents (n = 130; 15–19 years) were randomly assigned 1:1:1 to NET-EN, CCVR, or COCPs for 16 weeks, then subsequently crossed over to another HC for 16 weeks. Estrogen, follicular stimulating hormone (FSH), and luteinizing hormone (LH) levels were measured. Chemokine receptor 5 (CCR5), human leukocyte antigen (HLA) DR isotope, and cluster of differentiation 38 (CD38) expression by cervical cytobrush-derived CD4+ T cells was assessed by fluorescence-activated cell sorting. Th17 cells were defined as CCR6+ and CCR10-. Cervicovaginal Th17-related cytokines were measured by Luminex.ResultsCCVR use for the first 16 weeks was associated with reduced Th17 frequencies and lower FSH and LH concentrations, as compared to NET-EN and COCPs, with FSH concentrations and Th17 frequencies correlating significantly. However, Th17-related cytokine concentrations (interleukin [IL]-21, IL-1β, tumor necrosis factor–α, interferon-γ) and CCR5, HLA-DR, CD38, and Th17 frequencies were significantly higher in CCVR than NET-EN and COCP. At crossover, CCVR users changing to COCPs or NET-EN did not resolve activation or cytokines, although switching from COCP to CCVRs increased cytokine concentrations.ConclusionsCCVR use altered endogenous hormone levels and associated cervical Th17 cell frequencies to a greater extent than use of NET-EN or COCPs, although Th17 cells were more activated and Th17-related cytokine concentrations were elevated. While CCVRs may impact the HIV risk by regulating Th17 numbers, increased activation and inflammation may balance any risk gains.

A Qualitative Systematic Review of Women's Experiences Using Contraceptive Vaginal Rings: Implications for New Technologies.

Vaginal rings are available for contraception and hormone replacement, and are being developed as HIV/STD or multipurpose prevention technologies. A comprehensive understanding of women's expectations of and experiences with rings is urgently needed to inform product development and to optimize ring use. Three databases (PubMed, Global Health and CINAHL) were searched for English-language, peer-reviewed articles published between January 1996 and November 2017 that reported qualitative data on barriers to and facilitators of use of female-controlled contraceptive methods. Data on study methods, findings and conclusions pertaining to contraceptive rings were extracted, organized and analyzed. Twenty-six articles, all published since 2008, met the inclusion criteria. Seven studies focused largely or entirely on rings (and involved current, former or potential users), while the others focused on other contraceptive methods but included ring-specific data. Familiarity with the ring was low, and women commonly had initial concerns about the method-often related to insertion and removal, cleanliness and discomfort with touching their vagina-that were typically overcome over time. Other major themes were issues related to ring use and discontinuation, the importance of ring-related properties and characteristics, and considerations related to sexual partners and health care providers. Qualitative data have the potential to inform ring design and promotion. Future research should further explore women's expectations and experiences with the ring, the value of involving male partners in ring evaluation, and evaluation of interventions to improve patient-provider communication concerning ring choice and use.

Comprehensive overview of the recently FDA-approved contraceptive vaginal ring releasing segesterone acetate and ethinylestradiol: A new year-long, patient controlled, reversible birth control method

ABSTRACTIntroduction: This is an overview of the recently FDA-approved silicone elastomer combined hormonal contraceptive vaginal ring (CVR), which is used cyclically for up to 1 year, eliminating resupply challenges. This ring requires no refrigeration, simplifying the supply chain. Developed by the Population Council, this CVR will soon be marketed in the United States as Annovera™ by TherapeuticsMD.Areas Covered: The composition of the elastomer ring and the chemical, pharmacokinetic and pharmacodynamic properties of both hormonal components are discussed. Results of the clinical trials of its efficacy, tolerability, safety, and acceptability follow. Finally, subanalyses from the clinical trials are presented to guide clinicians in counseling potential users.Expert Opinion: This CVR introduces a new progestin – segesterone acetate (SA) – that has no androgenic or estrogenic action in vitro or in vivo, but has the highest anti-ovulatory potential of all available progestins. SA is paired with EE in an intravaginal elastomer ring, that is used cyclically (21 days in place/7 days removed) to provide 12 months (13 cycles) of contraception. This once-a-month, self-applied CVR offers a convenient, rapidly reversible, year-long contraception with efficacy and side effect profiles similar to other combined hormonal methods, for women with BMI < 29 kg/m2.

Don't put a ring on it! cerebral venous thrombosis with the combined hormonal contraceptive NuvaRing

Combined Hormonal Contraceptive (CHC) vaginal rings are used as an alternative to oral contraceptives with theoretical advantage of lower risk of thromboembolism. However, recent studies have shown that CHC vaginal rings may be as thrombogenic as oral forms. We present a case of complicated cerebral venous thrombosis (CVT) in a 29 year old using a vaginal contraceptive ring. A 29 year old woman presented to the emergency department with generalized seizure preceded by worsening headaches and left upper extremity weakness and numbness. Non-contrast CT revealed subarachnoid hemorrhage in bilateral frontal lobes. CT angiography revealed an occlusive thrombus within the superior sagittal sinus extending into the bilateral cerebral veins. MRI revealed infarcts in the adjacent cortices. The patient did not smoke and there was no history of prior vaso-occlusive events, hypercoagulable state, malignancy, infection or head trauma. Evaluation for inherited or acquired thrombophilia was negative. The patient was identified to have an etonogestrel/ethinyl estradiol vaginal ring (NuvaRing) for abnormal uterine bleeding. She was treated with intravenous heparin and later transitioned to Apixaban. The vaginal ring was removed. She was maintained on anti-convulsant medication and had no further seizures. At discharge, the patient had marked improvement with mild residual weakness and was ambulating independently. Combined Hormonal Contraceptive NuvaRing devices likely have prothrombotic potential comparable to oral contraceptives and increased recognition may promote earlier venous imaging and result in better clinical care and outcomes of stroke patients.

The Role of Contraception in the Past, Present and Future

Contraceptives play an undeniable important role in woman’s lives. It is widely accepted that the availability of both hormonal and non-hormonal modern contraceptives have improved 0 women’s lives worldwide by allowing women to control their own fertility. Indirectly, contraceptives have been shown to reduce maternal mortality, unwanted pregnancy, and overpopulation. However, the contraceptives available today may not be suitable for all users. Furthermore, there is still need to expand available current contraceptives choices especially long-term contraceptives in order to improve acceptability. As a result, several novel products such as implants, contraceptive vaginal rings, and transdermal patches have recently been introduced in family planning programs. Additional issue of contraceptive needed to be addressed is the adverse effects of hormonal contraceptives. Therefore, new combinations with an improved metabolic profile is currently being researched. Generally, the introduction of new methods with additional health benefits and less side effects would help women with their unmet needs to obtain access to a wider range of contraceptives.

Heavy Menstrual Bleeding in the Adolescent

Heavy menstrual bleeding is a common presenting problem in the adolescent population. The average age of menarche is between 12 and 13 years. The most common reason for heavy menstrual bleeding soon after menarche is from an immature hypothalamic ovarian access, which spontaneously resolves once cycles become ovulatory. However, the broad differential diagnosis for heavy menses in adolescents includes coagulopathy, thyroid disease, sexually transmitted infections, specifically chlamydia, and chronic medical conditions. Von Willebrand disease is the most common bleeding disorder that can present with heavy menstrual bleeding at menarche or shortly after. A thorough history and physical exam with occasional labs needs to be completed and can assist in narrowing the differential diagnosis. Treatment of heavy menstrual bleeding consists of hormonal and nonhormonal options: combination oral contraceptive pills, patches, or rings taken continuously or cyclically; progesterone-only pills; progesterone implants; progesterone intrauterine devices; cyclic tranexamic acid; cyclic aminocaproic acid; and GnRH agonists with add-back therapy. This review contains 3 tables, and 28 references. Key Words: adolescent menses, anovulation, bleeding disorder, heavy menstrual bleeding, immature hypothalamic ovarian axis, menarche, treatment of heavy menses, Von Willebrand disease

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.

Post-use ring weight and residual drug content as potential objective measures of user adherence to a contraceptive progesterone vaginal ring

ObjectivesThe primary aim was to investigate post-use ring weight as a potential measure of cumulative adherence to a progesterone-releasing vaginal ring. Study designWe weighed and quantified residual progesterone in 115 vaginal rings following 90-day use by participants in an acceptability trial conducted in Nigeria, Senegal and Kenya. The primary objective was to correlate residual progesterone content with post-use ring weight. Secondary objectives included correlating ring weight with putative duration of ring use, and, where participants used two rings consecutively in the study, correlating residual content between these paired rings. ResultsMean ring weight and progesterone content of used rings was 8.62±0.24 g and 1245±245 mg respectively, versus 9.37±0.02 and 2058±21 mg for control rings. Most used rings (90.4%) had residual progesterone levels less than 85% of the nominal loading. Linear regression showed a strong positive linear trend between residual progesterone content and post-use ring weight for all rings (r2=0.82). Duration of ring use was inversely associated (p=.00020) with ring weight. ConclusionsPost-use ring weight is highly correlated with residual progesterone content, a benchmark objective cumulative measure of adherence, and thus potentially useful as a surrogate objective measure of cumulative adherence to a progesterone-releasing vaginal ring. Implication statementFor vaginal rings containing a high initial drug loading and releasing a relatively large fraction of the initial loading during clinical use, post-use ring weight may offer a simple and inexpensive alternative to residual content testing for accurate monitoring of user adherence.

A new woman-controlled contraceptive vaginal ring: a global step forward

More than 40 years ago, the development of contraceptive vaginal rings began, based on the fact that the vaginal epithelium can absorb steroid hormones and the capacity of elastomers to release these hormones at almost constant rates.1 The growing interest in woman-controlled contraceptive methods has supported and accelerated the process.