Estetrol (E4) is an estrogen medication and naturally occurring steroid hormone which is used in combination with a progestin in combined birth control pills and is under development for various other indications. These investigational uses include menopausal hormone therapy to treat symptoms such as vaginal atrophy, hot flashes, and bone loss and the treatment of breast cancer and prostate cancer. It is taken by mouth.
Estetrol is a naturally occurring and bioidentical estrogen, or an agonist of the estrogen receptor, the biological target of estrogens like endogenous estradiol. Due to its estrogenic activity, estetrol has antigonadotropic effects and can inhibit fertility and suppress sex hormone production and levels in both women and men. Estetrol differs in various ways both from other natural estrogens like estradiol and synthetic estrogens like ethinylestradiol, with implications for tolerability and safety. For instance, it appears to have minimal estrogenic effects in the breasts and liver. Estetrol interacts with nuclear ERα in a manner identical to that of the other estrogens and distinct from that observed with Selective Estrogen Receptor Modulators (SERMs).
Estetrol was first discovered in 1965, and basic research continued up until 1984. It started to be studied again as well as investigated for potential medical use in 2001, and by 2008, was of major interest for possible medical use. As of 2021, estetrol is in mid- to late-stage clinical development for a variety of indications.
Estetrol is available in combination with drospirenone in the following formulations, brand names and indications:
Estetrol (as monohydrate) 15 mg and drospirenone 3 mg Nextstellis (CA, US and Australia) – combined oral contraception
Estetrol (as monohydrate) 15 mg and drospirenone 3 mg Drovelis (EU) – combined oral contraception
Estetrol (as monohydrate) 15 mg and drospirenone 3 mg Lydisilka (EU) – combined oral contraception
Minimal side effects have been observed with estetrol in women.
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NOTOC A sex-hormonal agent, also known as a sex-hormone receptor modulator, is a type of hormonal agent which specifically modulates the effects of sex hormones and of their biological targets, the sex hormone receptors. The sex hormones include androgens such as testosterone, estrogens such as estradiol, and progestogens such as progesterone. Sex-hormonal agents may be either steroidal or nonsteroidal in chemical structure and may serve to either enhance, inhibit, or have mixed effects on the function of the sex hormone systems.
Estrone (E1), sold under the brand names Estragyn, Kestrin, and Theelin among many others, is an estrogen medication and naturally occurring steroid hormone which has been used in menopausal hormone therapy and for other indications. It has been provided as an aqueous suspension or oil solution given by injection into muscle and as a vaginal cream applied inside of the vagina. It can also be taken by mouth as estradiol/estrone/estriol (brand name Hormonin) and in the form of prodrugs like estropipate (estrone sulfate; brand name Ogen) and conjugated estrogens (mostly estrone sulfate; brand name Premarin).
An estrogen (E) is a type of medication which is used most commonly in hormonal birth control and menopausal hormone therapy, and as part of feminizing hormone therapy for transgender women. They can also be used in the treatment of hormone-sensitive cancers like breast cancer and prostate cancer and for various other indications. Estrogens are used alone or in combination with progestogens. They are available in a wide variety of formulations and for use by many different routes of administration.