Estradiol

Estradiol is one of the main hormones that regulate the female reproductive system. It promotes ovulation and supports implantation if the egg (ovum) becomes fertilized. Aside from the reproductive system, estradiol also has effects on the heart, blood vessels, bones, and brain. 1

When a woman goes through menopause, ovulation stops, and estradiol levels fall. Low estradiol levels can present with various symptoms and may be very bothersome in daily life. Some women choose to undergo estradiol hormone replacement therapy (HRT), where a synthetic form of the hormone is taken to ease low estradiol symptoms. 2

Estradiol is also commonly taken together with progesterone in the combined oral contraceptive pill. 3

Estradiol is an important reproductive hormone. In women, it is mainly created by the ovaries, but small amounts are also produced by fat cells, and the adrenal glands. 4

Along with other reproductive hormones including progesterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), estradiol helps regulate the menstrual cycle. In particular, it makes sure that an ovum is matured and released from its follicle each month during ovulation. After ovulation, this follicle, now called the ‘corpus luteum’, begins to produce estradiol as well. 3 5

Men also produce some estradiol in their testes and adrenal glands. However, estradiol levels are much lower in men than they are in women. 5

In women, estradiol is key to healthy reproductive function. Its levels in the body begin to rise during puberty. Every month, estradiol helps an ovum mature and burst from its follicle during ovulation.

In the second half of the menstrual cycle, combined with progesterone, it also helps thicken the lining of the uterus. This ensures that, if fertilization occurs, the egg can implant and grow. 3 Estradiol levels drop naturally after a woman goes through menopause, as ovulation stops.

Although estradiol is predominantly involved in regulating the menstrual cycle, it also has many important effects on other body systems. It allows for the growth of breast tissue and secondary sexual characteristics, supports healthy cardiovascular function, and has numerous other effects on the neurological and skeletal systems. 1 5

Estradiol also acts on the neurological, skeletal and cardiovascular systems of men. 4

In the context of reproductive hormones, you may often see estrogen and estradiol used interchangeably. However, it is important to understand what differentiates these two terms. Estrogen is best defined as an umbrella term for a group of hormones. These are the four ‘estrogens’:

• Esterone
• Estradiol
• Estriol
• Estetrol

Of these hormones, estradiol is the most abundant, and the most important for women of reproductive age (most commonly between 15-49 years old). 1

In women, estradiol levels fluctuate throughout the menstrual cycle. During the first half of your cycle, or what is called the ‘follicular phase’, estradiol levels rise steadily, helping the ovum mature. Estradiol levels are at their highest directly before ovulation, then promptly drop after ovulation happens.

As the corpus luteum takes over estradiol production during the second half of your cycle, or ‘luteal phase’, estradiol levels are maintained until you get your period. 5

The National Health Service (NHS) in the UK has published the following normal reference ranges for estradiol: 5

• Days 1-14 (Follicular phase): 72-529 pmol/L
• Day 14 (Ovulation): 235-1309 pmol/L
• Days 14-28 (Luteal phase): 205-786 pmol/L

Estradiol levels drop after you go through menopause, stabilizing at <118 pmol/L. This happens because the ovaries stop producing it. In men, estradiol levels should not exceed 146 pmol/L. 4 5

Estradiol levels can be checked with a simple blood test. They are routinely monitored when you are undergoing hormone replacement therapy (HRT). It may be worth having your estradiol levels checked if you find yourself experiencing low or high estradiol symptoms.

When you go through menopause, your periods stop, and the production of estrogens by your ovaries drops. In most women, this can result in symptoms which can be troubling and bothersome in daily life. Some low estrogen symptoms can include: 4 1

• Hot flashes
• Night sweats
• Mood swings
• Irregular periods
• Insomnia
• Vaginal dryness
• Painful urination
• Painful intercourse
• Reduced libido
• Dry skin

If you are experiencing one or more of these low estrogen symptoms, whether you are of menopausal age (roughly between 45-55 years old) or not, you may wish to get your estradiol levels checked. This is because low estrogen can be caused by various conditions throughout the lifespan, not just menopause. Importantly, having low estrogen makes you more likely to develop osteoporosis, as estrogen plays a role in maintaining healthy bone turnover. 4

Adrenal gland enlargement, early puberty, and certain ovarian, adrenal, and testicular tumours can cause high estradiol levels in your body. 5 Both women and men can experience symptoms of high estradiol, although they manifest differently. Women often report: 4

• Irregular periods
• Fatigue
• Weight gain
• Reduced sex drive
• Fibrous cysts in the breasts
• Low mood

Men may experience: 4

• Erectile dysfunction
• Infertility
• Enlarged breasts

Many women take estradiol-containing combined oral contraceptive pills to prevent pregnancy. These pills contain a combination of a synthetic estradiol and a synthetic progesterone, and affect the reproductive system in two main ways: 3

1. Prevent ovulation from happening;
2. Thicken the mucus around the cervix, forming a barrier that prevents sperm from entering.

Examples of combined oral contraceptive pills currently available on the market include those containing drospirenone and ethinyl estradiol, and norgestimate and ethinyl estradiol. One pill is taken at the same time every day. Importantly, missed pills reduce the efficacy of the treatment. 6 7

Some women with low estradiol, or who are going through menopause, may also take estradiol HRT to relieve their symptoms and prevent complications such as osteoporosis. For women of reproductive age this is often a combination of estradiol and progesterone, though women who have gone through menopause or had a hysterectomy can take estradiol-only formulations.

Estradiol can be supplemented in many ways, including as pills, creams, implants, gels, patches, rings, or pessaries. 2

Estradiol replacement therapy may cause some side effects, which will usually resolve after the first three months of use. Common side effects include: 2

• Headaches
• Nausea
• Heartburn
• Breast tenderness
• Muscle cramps
• Vaginal bleeding

It is important to also make note of some of the more serious medical risks associated with HRT. Taking hormone replacement can increase your risk of thromboembolic (blood clot) disorders, cardiovascular disorders such as high blood pressure, and some types of cancer. 1

Also, keep in mind that each mode of HRT has a different risk and side effect profile. For example, the risk of developing blood clots is higher when taking estrogen pills. If you are worried about this, you might want to consider an estradiol cream or estradiol patch instead as these carry a lower risk. 2

It is always best to discuss the risk and benefit profile of any HRT with your healthcare provider. If they decide that it may not be in your best interest to take HRT, there are a number of alternative therapies available to ease low estradiol symptoms. These include lifestyle modification, physical therapy, and certain non-HRT medicines. 1 2

Q: What types of estradiol supplements exist?
A: There are many modes of estradiol supplementation available, including estradiol pills, patches, creams, gels, rings and pessaries, and implants.

Q: How long does it take for estradiol cream to work?
A: With daily use, you may begin to see improvement in your symptoms after 2 weeks. It takes up to a month for estradiol cream to reach its full effect. 8

Q: What are some of the main contraindications to estradiol HRT?
A: It may be inadvisable for you to take estradiol HRT in some situations. Contraindications include a history or known risk for uterine or breast cancer, or a history or known risk for increased blood clotting. 1

Q: When can I stop taking HRT?
A: Most women stop taking HRT a few years after they go through menopause, once their symptoms stabilize. 2