Phase I/II pharmacokinetic and pharmacodynamic evaluation of two levonorgestrel-only contraceptive patches in a multicenter randomized trial.

Abstract:

OBJECTIVES:To evaluate the pharmacokinetic and pharmacodynamic effects of two novel levonorgestrel (LNG)-only contraceptive patches. STUDY DESIGN:This multi-center Phase I/II trial randomized participants to use a 7-day transdermal patch designed to deliver a 40 mcg or 75 mcg daily LNG dose for 11 consecutive weeks; randomization was stratified by body mass index (BMI) <32 or 32-40 kg/m2. Evaluations occurred twice weekly for 5 weeks, then once weekly with supplemental visits for participants reporting a urinary LH surge. We evaluated pharmacokinetics via the weekly trough serum LNG concentrations (≥180 pg/mL considered therapeutic). The primary pharmacodynamic outcomes were cervical mucus and ovulation, evaluated using modified Insler cervical mucus scores and serum markers of ovulation. RESULTS:Randomization yielded similar groups. Of 121 enrolled women, 117 contributed analyzable data. Overall, mean LNG concentrations achieved with use of the 75 mcg patch [value] were roughly double those seen with the 40 mcg dose. Concentrations achieved in higher-BMI women (BMI=32-40 kg/m2) were 50% lower compared to lower-BMI women for both patches. During the study, 94/117 (80%) participants had at least one LNG concentration <180 pg/mL. Insler scores were ≥5 at least once in 102/117 (87%) of participants, and ovulation occurred at least once in 81/117 (69%). Sixty participants (51%) had at least one ovulation following an Insler score ≥5; this occurred most frequently among higher-BMI participants using the lower-dose patch (19/25, 76%). CONCLUSIONS:Women using two investigational LNG patches did not achieve consistent concentrations of LNG >180 pg/mL, an efficacy benchmark established in other studies with LNG implants, and they experienced high rates of ovulation as well as cervical mucus scores not supportive of high contraceptive efficacy. IMPLICATIONS:The novel LNG-only patches in this study may not adequately decrease pregnancy risk, particularly for higher-BMI women. Future studies of LNG-only contraceptive patches will need to employ higher LNG doses and assess the acceptability and safety of such dosing.

journal_name

Contraception

journal_title

Contraception

authors

Westhoff CL,Chen BA,Jensen JT,Barnhart K,Thomas M,Teal S,Blithe D

doi

10.1016/j.contraception.2018.04.007

subject

Has Abstract

pub_date

2018-04-18 00:00:00

eissn

0010-7824

issn

1879-0518

pii

S0010-7824(18)30143-4

pub_type

杂志文章
  • Women's satisfaction with birth control: a population survey of physical and psychological effects of oral contraceptives, intrauterine devices, condoms, natural family planning, and sterilization among 1466 women.

    abstract::User satisfaction and the physical and psychological effects of five commonly used contraceptive methods were investigated in a population survey among 1466 West German women. The focus was on effects attributed by current and past users to these methods, rather than objectively assessed effects, to shed further light...

    journal_title:Contraception

    pub_type: 杂志文章

    doi:10.1016/s0010-7824(99)00034-7

    authors: Oddens BJ

    更新日期:1999-05-01 00:00:00

  • Results of a safety and feasibility study of the diaphragm used with ACIDFORM Gel or K-Y Jelly.

    abstract:BACKGROUND:New strategies are needed for preventing HIV infection in women. One potential approach is female-initiated use of an effective topical microbicidal gel in combination with a cervical barrier such as the diaphragm. STUDY DESIGN:Randomized, placebo-controlled safety and feasibility trial of diaphragm with va...

    journal_title:Contraception

    pub_type: 杂志文章,随机对照试验

    doi:10.1016/j.contraception.2009.10.011

    authors: von Mollendorf CE,Van Damme L,Moyes JA,Rees VH,Callahan MM,Mauck CK,Puren AJ,Tweedy K,Taylor D

    更新日期:2010-03-01 00:00:00

  • Evaluation of shorter mifepristone to misoprostol intervals for second trimester medical abortion: a retrospective cohort study.

    abstract:OBJECTIVES:To assess shorter mifepristone-misoprostol intervals compared to current guidelines for second trimester medical abortion on total abortion time (mifepristone to fetal expulsion) and induction time (first misoprostol to fetal expulsion). METHODS:This retrospective cohort study included women who elected for...

    journal_title:Contraception

    pub_type: 杂志文章

    doi:10.1016/j.contraception.2020.06.009

    authors: Henkel A,Lerma K,Blumenthal PD,Shaw KA

    更新日期:2020-11-01 00:00:00

  • The IUB, a newly invented IUD: a brief report.

    abstract:OBJECTIVE:To evaluate the initial safety and effectiveness of the intrauterine ball (IUB), a copper intrauterine device that, upon insertion in the uterus, takes a three-dimensional spherical form. STUDY DESIGN:Fifteen women were followed for 1 year, with follow-up visits at 1, 3, 6, 9 and 12 months. RESULTS:The phys...

    journal_title:Contraception

    pub_type: 杂志文章,随机对照试验

    doi:10.1016/j.contraception.2013.10.017

    authors: Baram I,Weinstein A,Trussell J

    更新日期:2014-02-01 00:00:00

  • Another look at the Dalkon Shield: meta-analysis underscores its problems.

    abstract::Numerous non-comparative clinical trials of the Dalkon Shield appear to provide ample evidence that the Dalkon Shield was an effective IUD; they seem to yield little evidence that it was a dangerous device, nor markedly different from its contemporaries. Equating the performance of the Dalkon Shield IUD to that of the...

    journal_title:Contraception

    pub_type: 临床试验,杂志文章,meta分析,随机对照试验

    doi:10.1016/0010-7824(93)90060-k

    authors: Sivin I

    更新日期:1993-07-01 00:00:00

  • Effect of an oral contraceptive in primary dysmenorrhea--changes in uterine activity and reactivity to agonists.

    abstract::Mechanisms for the therapeutic effect of oral contraceptives in dysmenorrhea were studied by recording intrauterine pressure on the first day of menstrual bleeding in women with moderate to severe symptoms and after three weeks of oral contraceptive therapy (150 micrograms levonorgestrel + 30 micrograms ethinyl estrad...

    journal_title:Contraception

    pub_type: 杂志文章

    doi:10.1016/0010-7824(89)90026-7

    authors: Ekström P,Juchnicka E,Laudanski T,Akerlund M

    更新日期:1989-07-01 00:00:00

  • Serum 25-hydroxycholecalciferol levels in women using oral contraceptives.

    abstract::A study has been made of the serum 25-hydroxycholecalciferol (25-HCC) levels in six groups of women. Significant differences were found between the one pregnant group and the two reference groups as well as between the one pregnant group and two of the three groups using oral contraceptives. No significant differences...

    journal_title:Contraception

    pub_type: 杂志文章

    doi:10.1016/0010-7824(81)90029-9

    authors: Schreurs WH,van Rijn HJ,van den Berg H

    更新日期:1981-04-01 00:00:00

  • Emetine ditartrate: a possible lead for emergency contraception.

    abstract::Interception of pregnancy in its initial stage is an attractive and viable approach to contraception. A chemical agent, taken within the first few days of missed menses, intercepts the conception, which is expelled with menstrual flow. The main targets of such agents are the uterus, blastocyst and the growing trophobl...

    journal_title:Contraception

    pub_type: 杂志文章

    doi:10.1016/j.contraception.2003.12.011

    authors: Mehrotra PK,Kitchlu S,Dwivedi A,Agnihotri PK,Srivastava S,Roy R,Bhaduri AP

    更新日期:2004-05-01 00:00:00

  • Folate status and homocysteine levels during a 24-week oral administration of a folate-containing oral contraceptive: a randomized, double-blind, active-controlled, parallel-group, US-based multicenter study.

    abstract:BACKGROUND:This study investigated the effects of adding levomefolate calcium 0.451 mg (the calcium salt of L-5-methyltetrahydrofolate; Metafolin®) to an oral contraceptive containing ethinylestradiol (EE) 20 mcg/drospirenone (drsp) 3 mg on folate levels in healthy women seeking contraception. STUDY DESIGN:In this ran...

    journal_title:Contraception

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1016/j.contraception.2011.05.013

    authors: Bart S Sr,Marr J,Diefenbach K,Trummer D,Sampson-Landers C

    更新日期:2012-01-01 00:00:00

  • Study of the effect of ulipristal acetate on human sperm ability to interact with tubal tissue and cumulus-oocyte-complexes.

    abstract:OBJECTIVE:Ulispristal acetate (UPA) is a selective progesterone receptor modulator widely used for emergency contraception (EC). The described main mechanism of action is by inhibiting or delaying ovulation; however, the postovulatory effects of the drug are still on debate. Therefore, the aim of this study was to dete...

    journal_title:Contraception

    pub_type: 杂志文章

    doi:10.1016/j.contraception.2017.02.019

    authors: Zumoffen C,Gómez-Elías MD,Caille AM,Bahamondes L,Cuasnicú PS,Cohen DJ,Munuce MJ

    更新日期:2017-06-01 00:00:00

  • Treatment of pain during medical abortion.

    abstract::A structured literature review was undertaken to determine, in the context of early medical abortion, the proportion of women who require analgesia, the predictors of analgesia requirement and the most appropriate analgesia regimen. Studies from different centers show wide variations in analgesia use, but, overall, ar...

    journal_title:Contraception

    pub_type: 杂志文章,评审

    doi:10.1016/j.contraception.2006.03.002

    authors: Penney G

    更新日期:2006-07-01 00:00:00

  • Utility and drawbacks of continuous use of a copper T IUD for 20 years.

    abstract::This article examines interrelated questions concerning the extent of need for contraception in women 40 years and older and the degree to which that need can be served when use of collared T IUDs is initiated in women aged 25-35 years. Differentials in the impacts of intrauterine device (IUD) use on health issues in ...

    journal_title:Contraception

    pub_type: 杂志文章,评审

    doi:10.1016/j.contraception.2007.01.016

    authors: Sivin I

    更新日期:2007-06-01 00:00:00

  • A study of the efficacy of cervical ripening with nitric oxide donor versus placebo for cervical priming before second-trimester termination of pregnancy.

    abstract::This was a double-blind randomized control study to evaluate the efficacy of cervical priming by nitric oxide donor before second-trimester induced abortion. One-hundred healthy women with a singleton pregnancy between 14 and 20 weeks of gestation were randomized into either 40 mg isosorbide mononitrate or placebo, gi...

    journal_title:Contraception

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1016/s0010-7824(03)00170-7

    authors: Li CF,Chan CW,Ho PC

    更新日期:2003-10-01 00:00:00

  • Progestogen-only contraceptive use among women with sickle cell anemia: a systematic review.

    abstract::The use of progestogen-only contraceptives among women with sickle cell anemia has generated concerns about possible hematological and other clinical complications. Based on the literature, we assessed whether use of progestogen-only contraceptives is associated with adverse health effects among women with sickle cell...

    journal_title:Contraception

    pub_type: 杂志文章,评审

    doi:10.1016/j.contraception.2005.08.010

    authors: Legardy JK,Curtis KM

    更新日期:2006-02-01 00:00:00

  • Postabortal contraception with norethisterone enanthate injections.

    abstract::Intramuscular injection of 200 mg norethisterone enanthate (NET-EN) was given to five women on the day of first trimester abortion. The injection was repeated twice at eight-week intervals, and thereafter at twelve-week intervals for one year. Plasma samples were collected for FSH, LH/hCG, estradiol, progesterone and ...

    journal_title:Contraception

    pub_type: 杂志文章

    doi:10.1016/0010-7824(83)90020-3

    authors: Lähteenmäki P,Toivonen J,Lähteenmäki PL

    更新日期:1983-06-01 00:00:00

  • Mobile phone ownership, text messages, and contraceptive use: Is there a digital revolution in family planning?

    abstract:OBJECTIVES:This study aims to clarify the associations between mobile phone ownership use on family planning outcomes. Secondary analysis of DHS data finds that in certain contexts, mobile phone ownership may be related to increased FP uptake. STUDY DESIGN:Using recent data for women 15-49 from the Demographic and Hea...

    journal_title:Contraception

    pub_type: 杂志文章

    doi:10.1016/j.contraception.2019.10.004

    authors: Jadhav A,Weis J

    更新日期:2020-02-01 00:00:00

  • Contraceptive efficacy of lactational amenorrhea in urban Chilean women.

    abstract::The contraceptive efficacy of breastfeeding was assessed in 236 healthy urban women who were followed at monthly intervals during the first postpartum year. Proportional hazard models were used to evaluate the influence of time postpartum, menstrual status and breastfeeding pattern upon the risk of pregnancy. Time and...

    journal_title:Contraception

    pub_type: 杂志文章

    doi:10.1016/0010-7824(91)90072-n

    authors: Díaz S,Aravena R,Cárdenas H,Casado ME,Miranda P,Schiappacasse V,Croxatto HB

    更新日期:1991-04-01 00:00:00

  • Combined and national experience of postmenstrual IUD insertions of Nova-T and Copper-T in a randomized study.

    abstract::A randomized comparative study between Nova-T and Copper-T-200 was performed simultaneously in Denmark, Finland and Sweden. The results of 741 postmenstrual insertions with Nova-T and 780 with Copper-T are reported. The pregnancy rate of Nova-T was lower in every age and parity group. The pregnancy rate of Copper-T-20...

    journal_title:Contraception

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1016/s0010-7824(79)80004-9

    authors: Luukkainen T,Nielsen NC,Nygren KG,Pyörälä T,Allonen H

    更新日期:1979-01-01 00:00:00

  • Conformity with current guidelines on oral contraceptive prescribing for breastfeeding women: a New Mexico survey.

    abstract:BACKGROUND:National and international contraceptive guidelines reflect expert opinion that recommends against the use of estrogen-containing hormonal contraception in the early postpartum period. This study was undertaken to estimate providers' practices in prescribing hormonal contraception to breastfeeding women. ME...

    journal_title:Contraception

    pub_type: 杂志文章

    doi:10.1016/j.contraception.2006.06.007

    authors: Espey E,Ogburn T,Leeman L,Reddy S,Lee C,Qualls C

    更新日期:2006-11-01 00:00:00

  • Effect of a once weekly oral contraceptive upon gonadotrophin and gonadal steroid levels.

    abstract::A moderately effective oral progestogen contraceptive, R-2323 (13beta-ethyl-17alpha-ethynyl-17-hydroxy-gona-4,9,11-trien,3-one), was administered weekly in doses of 2.5 mg and 5 mg to 5 subjects each for 8 weeks. In 2 of the 10 treatment cycles of 2.5 mg and 4 of the 10 treatment cycles of 5 mg, progesterone levels i...

    journal_title:Contraception

    pub_type: 杂志文章

    doi:10.1016/0010-7824(74)90071-7

    authors: Tredway DR,Mishell DR Jr

    更新日期:1974-08-01 00:00:00

  • The Management of a patient with a fragmented intrauterine device embedded within the cervical canal.

    abstract::A 28-year-old woman presented with a malpositioned intrauterine device (IUD) that was fragmented and significantly entrenched within the cervical canal and myometrium. IUD malposition with concomitant device fragmentation and embedded segments, albeit rare, should be a consideration given the device's prevalence. ...

    journal_title:Contraception

    pub_type: 杂志文章

    doi:10.1016/j.contraception.2018.08.010

    authors: Korber PE,Goldstein BH

    更新日期:2019-01-01 00:00:00

  • The effect of some beta -adrenergic blocking agents on ovulation in rabbits.

    abstract::The effect of propanolol hydrochloride (PH) and oxprenolol hydrochloride (OH) on ovulation was studied in mature rabbits. PH-treated animals did not accept mating and ovulation was suppressed after forced mating. 5 of 6 OH-treated animals refused mating. No implantation sites or corpora lutea were found in the anim...

    journal_title:Contraception

    pub_type: 杂志文章

    doi:10.1016/s0010-7824(75)80036-9

    authors: Foda MS,Darwish NA,Shafeek AA,Sharaf EM,Zaki MA

    更新日期:1975-07-01 00:00:00

  • Effects of multiglycosides of Tripterygium wilfordii (GTW) on rat fertility and Leydig and Sertoli cells.

    abstract::Primary cultures of rat Leydig and Sertoli cells were used to evaluate the direct effects of GTW on testicular cells and to compare these to the effects of gossypol acetate. Both GTW and gossypol acetate can affect the survival of Leydig and Sertoli cells. But Sertoli cells are much more sensitive than Leydig cells, e...

    journal_title:Contraception

    pub_type: 杂志文章

    doi:10.1016/0010-7824(92)90069-6

    authors: Lan ZJ,Gu ZP,Lu RF,Zhuang LZ

    更新日期:1992-03-01 00:00:00

  • Controlled release of copper from an intrauterine device using a biodegradable polymer.

    abstract:BACKGROUND:The adverse effects of copper intrauterine devices (IUDs) such as abnormal bleeding, pain and cramps may be due in part to the burst release of copper ions during the first few months of usage. This study focuses on controlling the initial burst release of copper ions. STUDY DESIGN:This study evaluated in v...

    journal_title:Contraception

    pub_type: 杂志文章

    doi:10.1016/j.contraception.2015.08.014

    authors: Ramakrishnan R,B B,Aprem AS

    更新日期:2015-12-01 00:00:00

  • Prazosin, an adrenergic blocking agent inadequate as male contraceptive pill.

    abstract::The purpose of this study was to investigate the efficacy and the acceptability of Prazosin as a male contraceptive pill. Acceptable antifertility drugs for men are proving difficult to produce, and the possibility of using pharmacological agents to block selectively or to inhibit normal sperm transport through the ma...

    journal_title:Contraception

    pub_type: 杂志文章

    doi:10.1016/0010-7824(88)90008-x

    authors: Kjaergaard N,Kjaergaard B,Lauritsen JG

    更新日期:1988-06-01 00:00:00

  • Long-term effects of lonidamine on mouse testes.

    abstract::Lonidamine (LND) [1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid] is a well-known antispermatogenic drug. The aim of this study was to identify its possible long-term sequelae on the reproductive system of mice as compared with rats, where most data have been obtained until now. Sexually mature CD1 male mice wer...

    journal_title:Contraception

    pub_type: 杂志文章

    doi:10.1016/j.contraception.2005.05.019

    authors: Maranghi F,Mantovani A,Macrì C,Romeo A,Eleuteri P,Leter G,Rescia M,Spanò M,Saso L

    更新日期:2005-10-01 00:00:00

  • The effects of Norplant on clinical chemistry in Singaporean acceptors after 1 year of use: I. Haemostatic changes.

    abstract::A longitudinal study of coagulation parameters was carried out on 100 Singaporean acceptors using the levonorgestrel subdermal implants NORPLANT for contraceptive purposes. At the end of 1 year of use, results from this on-going study indicate that these subjects may have an increased predisposition to thrombosis as e...

    journal_title:Contraception

    pub_type: 杂志文章

    doi:10.1016/0010-7824(88)90103-5

    authors: Viegas OA,Singh K,Koh S,Singh P,Ratnam SS

    更新日期:1988-09-01 00:00:00

  • Performance of a checklist to exclude pregnancy at the time of contraceptive initiation among women with a negative urine pregnancy test.

    abstract:OBJECTIVE:Our objective was to measure the sensitivity and specificity of a six-item "pregnancy checklist" at excluding early- or luteal-phase pregnancy among women with a negative urine pregnancy test who were initiating contraception. STUDY DESIGN:This was a secondary analysis of the Contraceptive CHOICE Project, a ...

    journal_title:Contraception

    pub_type: 杂志文章

    doi:10.1016/j.contraception.2014.08.002

    authors: Min J,Buckel C,Secura GM,Peipert JF,Madden T

    更新日期:2015-01-01 00:00:00

  • Choice of the levonorgestrel intrauterine device, etonogestrel implant or depot medroxyprogesterone acetate for contraception after aspiration abortion.

    abstract:OBJECTIVE:Women who have abortions are at high risk of contraception discontinuation and subsequent unintended pregnancy. The objective of this analysis was to identify factors associated with choice of highly effective, long-acting, progestin-only contraceptive methods after abortion. STUDY DESIGN:Women presenting fo...

    journal_title:Contraception

    pub_type: 杂志文章

    doi:10.1016/j.contraception.2015.06.013

    authors: Steinauer JE,Upadhyay UD,Sokoloff A,Harper CC,Diedrich JT,Drey EA

    更新日期:2015-12-01 00:00:00

  • Doing more for less: identifying opportunities to expand public sector access to safe abortion in South Africa through budget impact analysis.

    abstract:OBJECTIVE(S):To estimate the costs of public-sector abortion provision in South Africa and to explore the potential for expanding access at reduced cost by changing the mix of technologies used. STUDY DESIGN:We conducted a budget impact analysis using public sector abortion statistics and published cost data. We estim...

    journal_title:Contraception

    pub_type: 杂志文章

    doi:10.1016/j.contraception.2017.07.165

    authors: Lince-Deroche N,Harries J,Constant D,Morroni C,Pleaner M,Fetters T,Grossman D,Blanchard K,Sinanovic E

    更新日期:2018-02-01 00:00:00