Estrogens

About estrogen

Estrogens are produced by the ovaries along with progesterone at certain stages of the menstrual cycle and their production is under control of follicle stimulating hormone (FSH) and luteunising hormone (LH) produced by the pituitary gland, which are in turn under the control of gonadotrophin releasing hormones produced by the hypothalamus in the brain.  

Different forms of estrogen

Estrogen exists in several forms and with different potencies:

• Estradiol, specifically 17-beta-estradiol or E2, is the major and most active form of natural estrogen in the body produced by the ovaries and is responsible for the main actions of estrogen
• Ethinyloestradiol is a synthetic form of 17-beta-estradiol that is more resistant to metabolism in the liver than natural estradiol but has the same biological activity. 
• oestradiol valerate is a prodrug (or precursor) of natural human oestradiol and is converted to 17-beta-estradiol by esterase enzymes in the blood and liver.  It is an effective form of estrogen used for intramuscular administration (injection) as it is absorbed slowly and lasts longer that estradiol itself. 
• Estrone or E1 becomes the most prominent form of natural estrogen during menopause, as estradiol drops, and is produced primarily in the adrenal glands.  Estrone is readily converted into a long lasting form estrone sulphate which concentrates in breast tissue of post-menopausal women and is thought to be involved the development of breast cancer, by being converted to estradiol.  
• Estriol or E3 is the weakest of the three natural forms of oestrogen.  It is the prominent form of estogen during pregnancy and is produced by the placenta, but plays no significant role in non-pregnant women as it is mild, short acting and normally present in small amounts.
• Conjugated oestrogens are a mixture of several different forms of estrogen (at least 10) isolated from horse urine.  They contain mainly forms of estrogen that are in the sulphate form and can be easily absorbed and converted to the active form estradiol.

Delivery methods for estrogens

Estrogen hormone replacement therapy is available in several different preparations and routes of administration.  These include:

• Oral preparations which are subjected to metabolism by the liver and is associated with side effects, such as painful swollen breasts, nausea, headache.
• Skin patches allow oestrogen to diffuse through the skin and into the blood and allows for lower doses to be used, as estrogen bypasses liver and is therefore, not subject to first pass metabolism by the liver.  It also provides more constant blood levels as it diffuses into the blood at a steady rate
• Topical transdermal creams and gels which are rubbed into the skin so that the estrogen diffused through the skin directly into the blood circulation, allowing the estrogen to be released slowly through the skin. 

Products available for estrogen hormonal therapy

The most commonly used estrogens as part of a feminising regime for transgender hormone therapy are the more potent forms of estrogen including estradiol (17-beta-estradiol), oestradiol valerate and conjugated oestrogens.  Estriol can also be used but is less effective.

• estradiol for oral administration, skin patch or injection
• oestriol for oral administration
• conjugated oestrogens for oral administration
• oestradiol valerate for injection