Pharmacodynamics<unk>  act as selective agonists of the<unk> receptors (ERs), the ERα and the ERβ. They may also bind to and activate membrane<unk> receptors (mERs) such as the GPER.<unk>  do not have off-target activity at other steroid hormone receptors such as the androgen, progesterone, glucocorticoid, or mineralocorticoid receptors, nor do they have neurosteroid activity by interacting with neurotransmitter receptors, unlike various progestogens and some other steroids. Given by subcutaneous injection in mice, estradiol is about 10-fold more potent than estrone and about 100-fold more potent than estriol.<unk>  have antigonadotropic effects at sufficiently high concentrations via activation of the ER and hence can suppress the hypothalamic–pituitary–gonadal axis. This is caused by negative feedback, resulting in a suppression in secretion and decreased circulating levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The antigonadotropic effects of<unk>  interfere with fertility and gonadal sex hormone production. They are responsible for the hormonal contraceptive effects of<unk> . In addition, they allow<unk>  to act as functional antiandrogens by suppressing gonadal testosterone production. At sufficiently high doses,<unk>  are able to suppress testosterone levels into the castrate range in men.<unk>  differ significantly in their pharmacological properties. For instance, due to structural differences and accompanying differences in metabolism,<unk>  differ from one another in their tissue selectivity; synthetic<unk>  like ethinylestradiol and diethylstilbestrol are not inactivated as efficiently as estradiol in tissues like the liver and uterus and as a result have disproportionate effects in these tissues. This can result in issues such as a relatively higher risk of thromboembolism. In-vitro pharmacodynamics In-vivo pharmacodynamics Pharmacokinetics<unk>  can be administered via a variety of routes, including by mouth, sublingual, transdermal/topical (gel, patch), vaginal (gel, tablet, ring), rectal, intramuscular, subcutaneous, intravenous, and subcutaneous implant. Natural<unk>  generally have low oral bioavailability while synthetic<unk>  have higher bioavailability. Parenteral routes have higher bioavailability.<unk>  are typically bound to albumin and/or sex hormone-binding globulin in the circulation. They are metabolized in the liver by hydroxylation (via cytochrome P450 enzymes), dehydrogenation (via 17β-hydroxysteroid dehydrogenase), and conjugation (via sulfation and glucuronidation). The elimination half-lives of<unk>  vary by<unk> and route of administration.<unk>  are eliminated mainly by the kidneys via the urine as conjugates.
Estrogen 
Estradiol 
Estradiol
Androgen
Sex hormone
Progesterone
Progesterone 
Estriol