E2; estradiol; 17-beta (o)estradiol
Oestradiol (E2) is a steroid hormone made from cholesterol and is the strongest of the three naturally occurring oestrogens (oestrone E1, oestradiol E2, oestriol E3). It is the main oestrogen found in women and has many functions, although it mainly acts to mature and maintain the female reproductive system. An increase in blood oestradiol levels as the follicles in the ovary grow during the menstrual cycle leads to an increase in luteinising hormone (LH) levels, which in turn results in an egg becoming mature (able to be fertilised by sperm) and released from the ovary (ovulation). Another important role of oestradiol is to thicken the lining of the uterus (called the endometrium) so that the egg can implant if it becomes fertilised by sperm. Oestradiol also promotes development of breast tissue and increases both bone and cartilage density.
Before the menopause, oestradiol is mostly made by the ovaries. Oestradiol levels vary throughout the monthly menstrual cycle, being highest at ovulation – around days 12-14 of the cycle, and lowest at menstruation (also known as a ‘period’), which usually occurs on days 1-5 of the cycle. Oestradiol levels in women reduce slowly with age, with a large decrease occurring at the menopause when the ovaries ‘switch off’. In pregnant women, the corpus luteum produces oestradiol in early pregnancy, and the placenta produces oestradiol during the latter part of pregnancy.
Men also produce oestradiol (from conversion of testosterone via the enzyme aromatase); however, the amount produced is much lower than in women. Within the testes, some testosterone is changed into oestradiol by the enzyme aromatase and this oestradiol is essential for the production of sperm. In both sexes, oestradiol is also made in much smaller amounts by fat tissue, the brain and the walls of blood vessels.
The production of oestradiol in women’s ovaries is controlled by hormones released from both the hypothalamus in the brain and the pituitary gland: this is called the hypothalamic–pituitary– gonadal (HPG) (or hypothalamic–pituitary–ovarian axis in women) axis. The hypothalamus, located at the base of the brain, releases a hormone called gonadotrophin-releasing hormone (GnRH). GnRH then acts on the pituitary gland to cause the release of two further hormones, namely luteinising hormone (LH) and follicle stimulating hormone (FSH). LH and FSH enter the blood stream to travel to and stimulate the ovary; in particular, LH and FSH act on the cells that surround each egg (these cells plus the egg form a unit called a follicle) and stimulates the follicle to grow and develop. As the follicle enlarges, the cells surrounding the egg (granulosa cells) will produce oestradiol. After the egg has been released from the follicle, the remainder becomes the corpus luteum. The corpus luteum produces both progesterone and oestradiol, which ensure that the lining of the uterus is fully prepared for implantation, should fertilisation occur and an embryo is formed that is ready to implant. The amount of oestradiol (and progesterone) in the circulation communicates with the hypothalamus and pituitary gland to control the development of the follicle, ovulation and the menstrual cycle.
It is unusual for women to have too much oestradiol outside of receiving hormonal treatments. Taking oestrogens as part of contraceptive pills, or as part of hormone replacement after menopause can be associated with an increased risk of clotting (in the legs or the lungs), and cancers (such as breast cancer), however these risks are small and the balance between risk and benefit will vary for women depending on factors such as the presence of other medical conditions and age.
In men, oestradiol levels can be slightly increased in conditions such as liver disease and obesity. This can lead to sexual dysfunction, decreased fertility decreased body hair, loss of muscle tone, increased body fat and excess breast tissue (gynaecomastia).
Oestradiol is necessary for bone development, so women with low oestradiol may be prone to developing osteoporosis, which can lead to an increased risk of fractures. Girls may also have low oestradiol if they have a delay in puberty, or have a disrupted / absent menstrual cycle (known as oligomenorrhoea or amenorrhoea). Oestradiol also has important roles in the brain, where low levels can be associated with psychological symptoms such as depression, fatigue or mood swings.
A woman’s oestradiol production falls naturally at the menopause and is responsible for many of its symptoms. Initially these include night sweats, hot flushes, vaginal dryness and mood swings, while in the longer term low oestradiol may increase the risk of osteoporosis. Oestrogens are also used in hormone replacement therapy (HRT) to relieve these symptoms of the menopause (see articles on menopause and ‘What is HRT?’ for more information).
Last reviewed: Jul 2021