Nestorone
Nestorone Uses, Dosage, Side Effects, Food Interaction and all others data.
Nestorone is a steroidal progestin or synthetic progesterone and a 19-norprogesterone derivative with no CH3 group radical in position 6 . In animal studies, segesterone acetate was shown to be one of the most potent progestins . It mediates progestational activity 100 times higher than that of progesterone . It is commonly sold under the brand names Nestorone and Elcometrine and serves as an active component in hormonal contraceptives. It is also used as a treatment for endometriosis in South American countries. Nestorone binds selectively to progesterone receptors and not androgen receptors . Due to its rapid hepatic metabolism, segesterone acetate must be administered parenterally . Nestorone is not an orally active compound, but it is proved to be a potent anti-ovulatory agent when given in implants, vaginal rings or percutaneous gel .
On August 10, 2018, Annovera™ containing segesterone acetate and ethinyl estradiol was granted approval by the U.S. Food and Drug Administration (FDA) as the first and only contraceptive that provides an entire year of protection against unintended pregnancy while entirely under a woman's control. According to the Center for Disease Control, more than 43 million women in the U.S. are at risk of unintended pregnancy, which may be associated with an elevated risk for improper prenatal care, premature and low-birth-weight infants, and physical and mental health risks . The introduction of this new contraceptive method offers an expansion of birth control options for women while maintaining high efficacy and acceptability similar to existing shorter-acting combined hormonal methods . In clinical trials, Annovera™ achieved a 97.3% success in pregnancy prevention . Annovera™ is administered as a vaginal ring that is in place for 21 days and removed for 7 days each cycle. As with other hormonal contraceptives, Annovera™ carries the risk for serious cardiovascular events.
Nestorone suppresses ovulation. In a Phase I randomized, placebo-controlled, randomized crossover study involving healthy adult female subjects, there was no clinically significant QTc interval prolongation following a single intravenous bolus dose of segesterone acetate . Nestorone shows no androgenic, anabolic, or estrogenic activity . It also did not show uterotropic activity in ovariectomized rats . In the endometrial transformation test to assess the progestational activity, dose-dependent increases in both uterine weight was observed following subcutaneous administration of segesterone acetate .
| Trade Name | Nestorone |
| Generic | Segesterone acetate |
| Segesterone acetate Other Names | Elcometrine, Nestorone, Segesterone acetate |
| Type | |
| Formula | C23H30O4 |
| Weight | Average: 370.489 Monoisotopic: 370.214409446 |
| Protein binding | Serum protein binding of segesterone acetate is approximately 95% and it displays negligible binding affinity for sex hormone-binding globulin (SHBG) . |
| Groups | Approved, Experimental, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Nestorone in combination with ethinyl estradiol is indicated for use by females of reproductive potential to prevent pregnancy as a combination hormonal contraceptive (CHC). It induces contraception for thirteen 28-day cycles (1 year) following vaginal administration. The vaginal system must remain in place continuously for 3 weeks (21 days) followed by a 1-week (7-day) vaginal system-free interval. The use in females with a body mass index of >29 kg/m^2 has not been adequately evaluated .
Nestorone is also used to associated treatment for these conditions: Hormonal Contraception
How Nestorone works
Nestorone selectively binds to the progesterone receptor (PR), a transcription factor belonging to the nuclear receptor superfamily, where it acts as an agonist and transactivator . According to the findings from docking experiments, it adopts the same docking position within the PR ligand-binding domain (LBD) as progesterone but due to additional stabilizing contacts between 17α-acetoxy and 16-methylene groups and PR LBD, segesterone acetate display higher potency than progesterone . As with other progestins, segesterone acetate prevents ovulation by blocking the midcycle surge in luteinizing hormone (LH) secretion, thereby inhibiting the development of ovarian follicles . When used in combination with segesterone acetate, ethinyl estradiol potentiates the antigonadotropic of the progestin and prevents irregular shedding of the endometrium . Nestorone lacks androgenic activity, and displayed binding affinity to androgen receptors that was 500- to 600-fold less than that of testosterone . It does not display binding affinity toward estrogen receptors . When the relative binding affinities of segesterone acetate to human steroid receptors were investigated in vitro, it was demonstrated that segesterone acetate binds to the glucocorticoid receptor . However, segesterone acetate did not exert any glucocorticoid activity in the in vivo assays showing no increase in liver glycogen and tyrosine transaminase TAT .
Toxicity
There have been no reports of serious ill effects from overdose of combination hormonal contraceptive use. Overdosage may cause withdrawal bleeding in females and nausea. In case of suspected overdose, all vaginal systems containing segesterone acetate should be removed and symptomatic treatment should be initiated .
In a 2-year carcinogenicity study in rats receiving segesterone acetate via subdermal implants, there was no drug-related increase in tumor incidence. In a 2-year intravaginal carcinogenicity study in mice, segesterone acetate gel produced an increased incidence of adenocarcinoma and lobular hyperplasia in the breast at a supratherapeutic dose of 30 mg/kg/day. Nestorone was not shown to be mutagenic or clastogenic .
Food Interaction
- Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of segesterone acetate. If coadministration is necessary, back up contraception should be used.
Volume of Distribution
The volume of distribution of segesterone acetate is 19.6 L/kg .
Elimination Route
Contraceptive vaginal rings provided sustained release of contraceptive levels of segesterone acetate over 90 days in a pharmacokinetic study of healthy women . Following vaginal administration for up to 13 cycles, segesterone acetate was absorbed into systemic administration and reached the peak plasma concentration in 2 hours in Cycle 1, Cycle 3, and Cycle 13. Concentrations declined after time to reach plasma concentration (Tmax) and became more constant after 96 hours post-dose.Over subsequent cycles of use, the peak serum concentrations of segesterone acetate decreased. In Cycle 1, 3 and 13, the peak plasma concentrations were 1147, 363, and 294 pg/mL .
Half Life
The mean (SD) half life of segesterone acetate is 4.5 (3.4) hours .
Clearance
No pharmacokinetic data available.
Elimination Route
In a pharmacokinetic study, approximately 81.4% and 7.62% of the subcutaneously-administered dose in rats was excreted via feces and urine, respectively .
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