Contraception in the Era of COVID-19 Nanda, Kavita; Lebetkin, Elena; Steiner, Markus J ...
Global health science and practice,
06/2020, Letnik:
8, Številka:
2
Journal Article
Recenzirano
Odprti dostop
As global health systems and communities prepare to meet an unprecedented threat causing increased demands for the care of people with COVID-19, health care providers should strive to ensure ...continuity of reproductive health care to women and girls in the face of facility service disruption.
In the face of facility service disruptions due to COVID-19, health care providers, particularly in low- and middle-income countries, should strive to maintain continuity of reproductive health care to women and girls as an essential service.
When in-person encounters are limited, health care providers should adapt the way contraceptive services are provided by using telehealth whenever possible for counseling, shared decision making, and side effect management, and should make adjustments to provision of contraceptive methods to ensure access.
To evaluate the pharmacokinetics and pharmacodynamics of medroxyprogesterone acetate after a single subcutaneous injection in the abdomen of 150 or 300 mg Depo-Provera and compare results to two ...injections of Depo-SubQ Provera 104 given 3 months apart.
Partially randomized, multicenter, parallel-group study.
Research unit.
Forty-two women of reproductive age with confirmed ovulatory cycle and body mass index of 18–35 kg/m2.
Women received a single subcutaneous injection of 150 mg (n = 24) or 300 mg (n = 9) of Depo-Provera or two injections of Depo-SubQ Provera 104 (n = 9).
Suppression of ovulation as measured by progesterone, serum medroxyprogesterone acetate concentrations, and estimated pharmacokinetics parameters.
No ovulations were observed during 7 months after a single injection of 150 or 300 mg Depo-Provera. The 150 mg group had a similar Cmax as observed over two injection cycles of Depo-SubQ Provera 104 and a similar 6-month trough concentration as the 3-month trough of Depo-SubQ Provera 104.
Our pharmacodynamics and pharmacokinetics data provide proof of concept that Depo-Provera (150 mg) may be an effective contraceptive method when injected subcutaneously every 6 months, with up to a 4-week grace period for reinjections.
NCT02456584.
Ensayo clínico para la evaluación de la farmacocinética y farmacodinámica del acetato de medroxiprogesterona tras la administración subcutánea de Depo-Provera.
Evaluar la farmacocinética y farmacodinámica de acetato de medroxiprogesterona después de una única inyección subcutánea abdominal de 150 o 300 mg de Depo-Provera y comparar los resultados con dos inyecciones de Depo-SubQ Provera 104 administradas con un intervalo de 3 meses.
Estudio multicéntrico, parcialmente aleatorizado y en grupos paralelos.
Unidad de investigación.
Cuarenta y dos mujeres en edad reproductiva con ciclos ovulatorios confirmados e índice de masa corporal entre 18 y 35 kg/m2.
Las mujeres recibieron una única inyección subcutánea de 150 mg (n=24) o 300 mg (n=9) de Depo-Provera o dos inyecciones de Depo-SubQ Provera 104 (n=9).
Supresión de la ovulación determinada por progesterona, concentraciones séricas de acetato de medroxyprogesterona y estimación de los parámetros farmacocinéticos.
No se observaron ovulaciones durante 7 meses después de una única inyección de 150 o 300 mg de Depo-Provera. El grupo de 150 mg tuvo una Cmax similar a la observada con dos ciclos de inyección de Depo-SubQ Provera 104 y una concentración similar durante 6 meses a la de Depo.SubQ Provera 104 durante 3 meses.
Nuestros datos farmacodinámicos y farmacocinéticos proporcionan la “prueba de concepto” de que la Depo-Provera (150 mg) puede ser un método contraceptivo eficaz inyectado cada 6 meses vía subcutánea, con hasta 4 semanas de período de gracia para las re-inyecciones.
Medroxiprogesterona acetato depot, subcutánea, contracepción, farmacocinética, supresión de la ovulación.
Access to safe and effective contraceptive choices is a reproductive right and contributes tremendously to improvements in maternal and child health. Progestin-only injectables, particularly ...intramuscularly injected depot medroxyprogesterone acetate (DMPA-IM), have received increased attention given findings suggesting a potential association with increased HIV risk. For women at high risk of HIV, the World Health Organization's Medical eligibility criteria for contraceptive use currently aggregate recommendations for all progestin-only injectables, including DMPA-IM, subcutaneously injected DMPA (DMPA-SC) and intramuscularly injected norethindrone/ norethisterone enanthate (NET-EN), except in the case of some drug interactions. We considered whether published data indicate differences or similarities between these injectables relevant to risk of acquiring HIV. In vitro data confirm different biological activities of these distinct progestins, including that MPA, and not NET, binds and activates the glucocorticoid receptor resulting in different biological effects relevant to immune function. Limited clinical data suggest changes in immunologic activity following DMPA-IM and NET-EN initiation, but interstudy variation and study design differences diminish ability to determine clinical relevance and the degree to which DMPA-IM and NET-EN could act differentially. The highest-quality epidemiologic studies suggest a potential 40% increase in HIV incidence in users of DMPA-IM relative to women not using hormonal contraception but no significant increase in risk in users of NET-EN. In our opinion, most of the available biologic activity and epidemiologic data indicate that DMPA and NET-EN are likely to act differently, and data remain too limited to evaluate differences between DMPA-IM and DMPA-SC.
This study aimed to evaluate and compare local tolerability of investigational drug TV-46046 and reference drug Depo-subQ Provera 104, both containing medroxyprogesterone acetate (MPA) as an active ...ingredient.
We conducted a randomized, crossover, single-center study. Twenty-seven healthy women aged 25 to 47 years at low risk of pregnancy received a subcutaneous injection of each of the four study drugs (120 mg/0.3 mL of TV-46046, 60 mg/0.3 mL of diluted TV-46046, 0.3 mL of TV-46046 placebo, and 104 mg/0.65 mL of Depo-subQ 104) in different quadrants of the abdomen. We assessed local tolerability by occurrence of injection site reactions (ISRs), as well as injection site pain and overall safety for at least 9 months postinjections.
Of a total of 108 study injections, three injections were partial due to needle blockage. We observed a total of 30 ISRs following 105 full-dose injections, including hypopigmentation (n = 24), bruising (n = 4), and atrophy/dimple (n = 2). Eleven cases of hypopigmentation occurred following 25 full-dose injections of undiluted TV-46046 (44.0%), six following 27 full-dose injections of diluted TV-46046 (22.2%), and seven following 26 full-dose injections of Depo-subQ 104 (26.9%). Hypopigmentations occurred on average 8 months postinjection. Injection pain was minimal and dissipated quickly after all four injections.
Subcutaneous administration of MPA in a suspension formulation is associated with the delayed onset of hypopigmentation at the site of injection. Although not statistically significant, the rate of ISRs was over 60% higher for undiluted TV-46046 compared to Depo-subQ 104. This difference bears careful monitoring in future studies of TV-46046.
From a safety standpoint, investigational drug TV-46046 is appropriate for further clinical testing as a 6-month contraceptive injectable. The previously underreported hypopigmentation associated with subcutaneous administration of MPA warrants further investigation and acceptability assessment among users of existing Depo-subQ 104 as well as careful monitoring of local tolerability of TV-46046 in future clinical trials.
Registered at clinicaltrials.gov no: NCT02817464
To characterize the relationship between serum medroxyprogesterone acetate (MPA) concentrations and ovulation suppression, and to estimate the risk of ovulation for investigational subcutaneous ...regimens of Depo-Provera CI (Depo-Provera) and Depo-subQ Provera 104 (Depo-subQ).
We performed a secondary analysis of 2 studies that assessed the pharmacokinetics and pharmacodynamics of MPA when Depo-Provera is administered subcutaneously rather than by the labeled intramuscular route. Each woman received a single 45 mg to 300 mg subcutaneous injection of Depo-Provera, a single 104 mg subcutaneous injection of Depo-subQ, or 2 injections of Depo-subQ at 3-month intervals. We used an elevation of serum progesterone ≥4.7 ng/mL as a surrogate for ovulation and non-parametric statistical methods to assess pharmacokinetic and pharmacodynamic relationships.
This analysis included 101 women with body mass index (BMI) 18 to 34 kg/m2. Return of ovulation occurred at a median MPA concentration of 0.07 ng/mL (95% CI: 0.06–0.08) and the 90th percentile was 0.10 ng/mL (95% CI: 0.09–0.14). Neither age, race, nor BMI significantly influenced this relationship. The estimated probabilities of ovulation within 4 months of a 104 mg subcutaneous injection and within 7 months of a 150 mg subcutaneous injection (6 plus a 1-month grace) were each below 2.2%.
The typical MPA concentration associated with loss of ovulation suppression is substantially less than the commonly cited threshold of 0.2 ng/mL. Based on our results, MPA levels would rarely be low enough to permit ovulation if the Depo-subQ reinjection interval were extended to four months or if 150 mg Depo-Provera were injected subcutaneously every 6 months.
Extending the three-month Depo-subQ reinjection interval by one month would result in a 25% reduction in yearly MPA exposure, with little risk of pregnancy. Off-label subcutaneous administration of 150 mg Depo-Provera every 6 months would be a highly effective repurposing of an excellent product, with a similar reduction in cumulative exposure.
Nowadays there are multiple types of contraceptive methods, from reversible to permanent, for those choosing to delay pregnancy. Misconceptions about contraception and infertility are a key factor ...for discontinuation or the uptake of family planning methods. Regaining fertility (the ability to conceive) after contraceptive discontinuation is therefore pivotal. Technical studies to date have evaluated return to fertility by assessing pregnancy as an outcome, with variable results, or return to ovulation as a surrogate measure by assessing hormone levels (such as progesterone, LH, FSH) with or without transvaginal ultrasound. In general, relying on time to pregnancy as an indicator of return to fertility following contraceptive method discontinuation can be problematic due to variable factors independent of contraceptive effects on fertility, hormone clearance, and fertility recovery. Since the ability to conceive after contraceptive method discontinuation is a critical factor influencing product uptake, it is important to have robust biomarkers that easily and accurately predict the timing of fertility return following contraception and isolate that recovery from extrinsic and circumstantial factors. The main aim of this review is to summarize the current approaches, existing knowledge, and gaps in methods of evaluating return-to-fertility as well as to provide insights into the potential of new biomarkers to more accurately predict fertility restoration after contraceptive discontinuation. Biomarker candidates proposed in this document include those associated with folliculogenesis, cumulus cell expansion, follicular rupture and ovulation, and endometrial transport and receptivity which have been selected and scored on predefined criteria meant to evaluate their probable viability for advancement. The review also describes limitations, regulatory requirements, and a potential path to clinically testing these selected biomarkers. It is important to understand fertility restoration after contraceptive method discontinuation to provide users and health providers with accurate evidence-based information. Predictive biomarkers, if easy and low-cost, have the potential to enable robust evaluation of RTF, and provide potential users the information they desire when selecting a contraceptive method. This could lead to expanded uptake and continuation of modern contraception and inform the development of new contraceptive methods to widen user's family planning choices.
Abstract Objectives A longer-acting injectable contraceptive that lasts for 6 months would be a valuable addition to the contraceptive method mix and ideal for women who are interested in spacing ...births and/or uncertain about their future reproductive plans. Here we review past applications of drug delivery technologies to injectable contraceptives as well as recent advancements in sustained drug delivery technologies that hold promise for the development of a new longer-acting injectable contraceptive product. Study design A global landscape analysis was conducted, promising sustained drug delivery technologies, and research opportunities and partnerships were established with experts in the fields of contraception and drug delivery to identify new approaches in developing a longer-acting injectable contraceptive product. Results The landscape analysis confirmed that a number of existing polymer systems, such as poly-lactic-co-glycolic acid and poly(epsilon-caprolactone), remain promising candidates for application to a longer-acting injectable product. Novel polymers and materials also hold promise for achieving longer release profiles and/or having other advantages over existing polymer systems, but products using these materials could potentially have longer roads to regulatory approval. Additionally, recent advancements in the manufacturing process of microspheres may benefit the development of a longer-acting injectable contraceptive. Conclusion The design of any new injectable product must take into account the limitations of current injectable contraceptives and address concerns that women may have for a longer-acting product. FHI 360 is supporting several research collaborations for proof of concept of various drug delivery approaches for achieving longer-acting product that fits an established target product profile.
Abstract Background The abdomen and thigh are recommended injection sites in the label for Depo-SubQ Provera 104™. We evaluated the pharmacokinetic profile of medroxyprogesterone acetate (MPA) ...following injection of Depo-SubQ Provera 104 in the upper arm, a preferred injection site in developing countries. Study design Twenty-six women in Norfolk, VA, received a single injection of Depo-SubQ Provera 104 in the upper arm in this prospective noncomparative study. We measured MPA serum concentrations prior to injection (day 1) and 11 times postinjection (days 2, 4, 8, 14, 30, 44, 60, 74, 91, 104 and 120). Results Serum MPA levels peaked at 0.953 ng/mL 2–14 days (interquartile range; median=8) after dosing. Mean AUC0–91 was 45.1 ng·day/mL. Mean MPA levels at days 91, 104 and 120 were 0.427, 0.367 and 0.327 ng/mL, respectively. A total of 15 individual measurements of MPA were below 0.2 ng/mL. All women but one had MPA levels above 0.1 ng/mL on day 91. Conclusions Injection of Depo-SubQ Provera 104™ in the upper arm provided sufficient MPA levels for contraceptive protection for 3 months (13 weeks). The uptake and metabolism of MPA when injected in the upper arm may be different from the abdomen and thigh.
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