Estradiol Valerate and Dienogest: A Novel Four-Phasic Oral Contraceptive Pill Effective for Pregnancy Prevention and Treatment of Heavy Menstrual Bleeding

Abstract

Estradiol valerate and dienogest have been combined to create a novel four-phasic oral contraceptive pill effective for both pregnancy prevention and treatment of heavy menstrual bleeding. This formulation represents the only oral contraceptive pill available in the USA containing an estrogen component that is biologically active as the endogenous estrogen 17β-estradiol. This medication was developed out of efforts to replace the most common estrogen in contraceptive pills, ethinyl estradiol, which is known to be a potent inducer of hepatic protein synthesis. Estradiol valerate has been available since the 1970s in oral and injectable forms indicated for the treatment of menopausal climacteric symptoms. Dienogest has been used in other oral contraceptive pills for over 10 years. Previous attempts to develop an oral contraceptive pill with natural estradiol or estradiol valerate were unsuccessful due to poor cycle control. A novel dynamic-dosing regimen was devised to improve the bleeding pattern. This medication has been shown in several clinical trials to have good contraceptive efficacy and cycle control. Recent studies have also demonstrated that this medication is effective for the treatment of heavy menstrual bleeding. However, compared with other oral contraceptive pills, this medication is associated with a higher frequency of absent withdrawal bleeding. Furthermore, the dynamic dosing regimen requires relatively complex instructions for users who miss pills.

A New Contraceptive Pill Containing 17β-Estradiol and Nomegestrol Acetate

“…The progestin in this pill is dienogest, a 19 nortestosterone derivative that has strong progestogenic activity in vivo. This pill is quadri phasic, containing 3 mg of E2 valerate alone in the first three pills and an association of E2 valerate and dienogest in the next 22 pills and three pills containing placebo [21][22][23]. It was approved by the US FDA in May 2010 and is marketed by Bayer Healthcare Pharmaceuticals (NJ, USA).…”

Elevated plasma oxytocin levels and higher satisfaction with life in young oral contraceptive users

“…Ethinylestradiol is unable to bind to SHBG and the total serum concentration is bioavailable 39 . Similarly, progestins have an unusually high percentage of unbound form in the blood 40 . Therefore, SHBG and corticosterone-binding globulin is assumed to have minimal impact on the signaling efficacy of ethinyl-estradiol and progestins.…”

How to reduce the number of side effects produced by COCs and improve adherence: simple tips for practitioners

“…Комби-нация ДНГ с E2В в препарате Клайра ® в режиме четырех-фазного дозирования с уменьшением («step down») эстрогенного компонента и одновременным увеличени-ем («step up») прогестинового компонента способна придать стабильность циклу. Биологический эффект E2В в дозе 2 мг/сут соответствует приблизительно 20 мкг этинилэстрадиола (ЭЭ) в отношении эффектов на уровне гипотоламо-гипофизарной оси и эффектов на уровне периферических тканей-мишеней [12].…”

“…В 80-90-х гг. появилось несколько исследова-ний, в которых было доказано, что прием КОК приводит к потерям витаминов и минералов, самыми уязвимыми из которых оказались витамины B 2 , B 6 , B 12 , фолиевая кисло-та, витамин С, магний, цинк и селен [22]. У 75% женщин, принимающих КОК, обнаружен дефицит В 6 [23], у 50% [24].…”