Phase II dose-finding study on ovulation inhibition and cycle control associated with the use of contraceptive vaginal rings containing 17β-estradiol and the progestagens etonogestrel or nomegestrol acetate compared to NuvaRing

Duijkers, Ingrid; Klipping, Christine; Heger-Mahn, Doris; Fayad, Ghassan N.; Frenkl, Tara L.; Cruz, Sandra M. A.; Korver, Tjeerd

doi:10.1080/13625187.2018.1506101

Cited by 7 publications

(5 citation statements)

References 15 publications

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“…Model simulations confirm that low and high doses of exogenous progestin reduce the LH surge to non-ovulatory levels as suggested by clinical data [16,17] for progestin treatments. Also low and high doses of exogenous estrogen reduce the LH surge to non-ovulatory levels.…”

Section: Introductionsupporting

confidence: 54%

“…Ovulation is broken into two stages and the luteal phase into four stages. Equations calculating ovarian hormones, assumed proportional to masses in different stages, are in Eqs 14- (17). In Eqs (14) and 15exogenous doses of estrogen (e dose ) and progestin (p dose ) are added, respectively.…”

Section: Plos Computational Biologymentioning

confidence: 99%

“…This occurs in our model because FSH synthesis is suppressed only by inhibin A (see Eq (3)). In our model of contraception, ovulation does not occur so the corpus luteum does not develop and InhA is produced at low levels (see Eq (17)). Hence, a considerable amount of FSH is synthesized and the FSH profile is high.…”

Section: Progestin Based Contraceptionmentioning

confidence: 99%

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Mechanistic model of hormonal contraception

et al. 2020

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Contraceptive drugs intended for family planning are used by the majority of married or inunion women in almost all regions of the world. The two most prevalent types of hormones associated with contraception are synthetic estrogens and progestins. Hormonal based contraceptives contain a dose of a synthetic progesterone (progestin) or a combination of a progestin and a synthetic estrogen. In this study we use mathematical modeling to understand better how these contraceptive paradigms prevent ovulation, special focus is on understanding how changes in dose impact hormonal cycling. To explain this phenomenon, we added two autocrine mechanisms essential to achieve contraception within our previous menstrual cycle models. This new model predicts mean daily blood concentrations of key hormones during a contraceptive state achieved by administering progestins, synthetic estrogens, or a combined treatment. Model outputs are compared with data from two clinical trials: one for a progestin only treatment and one for a combined hormonal treatment. Results show that contraception can be achieved with synthetic estrogen, with progestin, and by combining the two hormones. An advantage of the combined treatment is that a contraceptive state can be obtained at a lower dose of each hormone. The model studied here is qualitative in nature, but can be coupled with a pharmacokinetic/pharamacodynamic (PKPD) model providing the ability to fit exogenous inputs to specific bioavailability and affinity. A model of this type may allow insight into a specific drug's effects, which has potential to be useful in the pre-clinical trial stage identifying the lowest dose required to achieve contraception.

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Section: Introductionsupporting

confidence: 54%

Section: Plos Computational Biologymentioning

confidence: 99%

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Mechanistic model of hormonal contraception

et al. 2020

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“…With the second combined hormonal pill containing E2 and nomegestrol acetate in a 24/4 regimen, women experienced a decrease in unscheduled bleeding over time and increase in amenorrhea with continued use [22]. Bleeding patterns with investigational CVRs containing E2 and various doses of nomegestrol or etonogestrel showed that unscheduled bleeding decreases over time with all rings; however, bleeding predictability may not compare with ethinyl estradiol-based contraceptives [23,24]. In this study, we evaluated CVRs containing three doses of E2 combined with a progestin dose that effectively suppresses follicular development and endogenous ovarian estrogen synthesis.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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“…In vitro and in vivo studies have shown that E4 does not induce hepatic synthesis of SHBG and does not affect the activity of cytochrome P450, which inhibits ovulation in a dose-dependent manner and which acts as estrogen in the vagina, uterus and bone [55]. These premises have supported phase II studies with the use of E4 as an OC in combination with DRSP or LNG, which have shown efficacy in inhibiting ovulation, with a low metabolic impact on the synthesis of liver proteins [56][57][58]; phase III studies show the efficacy and safety of the OC containing 15 mg of E4+3 mg of DRSP [59].…”

Section: Prospects For the Future Of Oc With Natural Estrogenmentioning

confidence: 93%

Family Planning

Maria Paoletti,

Benedetto Melis,

Piras

et al. 2024

Obstetrics and Gynecology

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The contraception (the term is the fusion between “contra”, against, and conception): includes all methods that prevent conception. According to the physiology of human reproduction, the contraceptive methods can prevent the fecundation by hindering the female and male gametes meeting. In these mechanisms we include: The abstinence by sexual intercourse around the ovulatory phase of the cycle; The use of barriers that block contact between male gametes and female genitalia; The use of methods impeding the ascent of spermatozoa through the female genital tracts (intrauterine devices). The prevention of the oocyte from being available (hormonal contraceptives or oral contraceptives, OC). In this category there is the availability of short acting reversible contraception (SARC) (pill, vaginal ring, patch), and the long acting reversible contraception (LARC) (progestin implants). The ideal contraceptive method has to respond to four fundamental principles: efficacy, safety, reversibility, tolerability. The authors will discuss all the above contraceptive methods with the evaluation of indications and contraindications to each method.

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Phase II dose-finding study on ovulation inhibition and cycle control associated with the use of contraceptive vaginal rings containing 17β-estradiol and the progestagens etonogestrel or nomegestrol acetate compared to NuvaRing

Cited by 7 publications

References 15 publications

Mechanistic model of hormonal contraception

Mechanistic model of hormonal contraception

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

Family Planning

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