Hormone Therapy And Endometriosis: A Quick Guide

Endometriosis is an inflammatory condition that affects 10%¹ of women of reproductive age.

It is characterized by infertility and debilitating pelvic pain which is often cyclical and can get worse over time. You might feel pain during sex (dyspareunia), menstruation (dysmenorrhea), or when using the toilet (dyschezia and dysuria).

The condition occurs when endometrial cells grow outside of the uterus — typically in the lining of the abdominal cavity (peritoneum), bowel, bladder, ovaries, or fallopian tubes. These cells are also affected by the hormones that control the menstrual cycle, meaning that endometriosis tissue breaks down and bleeds. This can cause painful swelling, inflammation, scarring, and lesions because there is nowhere for the broken-down tissue to go.

Besides pain-relieving medications like acetaminophen (paracetamol) and nonsteroidal anti-inflammatory drugs (NSAIDs)², surgery, and alternative therapies, hormone therapy can effectively help treat the condition.

How do hormone therapies treat endometriosis?

Hormone therapies can help treat endometriosis and relieve symptoms. Combined hormonal contraceptives are a type of hormone therapy, but not all hormone therapies used to treat endometriosis have birth control effects.

The condition relies on estrogen³, a female sex hormone that encourages the growth of endometriosis tissue. Hormone therapies can regulate estrogen production and ease endometriosis symptoms.

Just like periods, the breakdown of endometriosis tissue is put on pause during pregnancy because eggs are not released. Some types of hormone therapy mimic the hormonal patterns in pregnancy, preventing the release of eggs — this is what first led doctors to prescribe oral contraceptives to treat endometriosis.

How does endometriosis prevent conception?

Unfortunately, endometriosis often causes infertility⁴. There are different reasons for this, including:

• Overproduction of cytokines (proteins that increase inflammation)

• Scar tissue and adhesions

• Blocked fallopian tubes

If you would like to get pregnant, your doctor is unlikely to prescribe contraceptive hormonal therapy to treat your endometriosis. They might suggest other interventions such as surgery or assisted reproductive techniques (ART).

Combined hormonal contraceptives

A combination of estrogen and progestin is thought to help slow the progression of endometriosis⁵. A 2015 review⁶ found that taking oral contraceptives continuously (skipping the sugar pills) reduced the recurrence of endometriosis and reduced pain more effectively than cyclical use.

The combined pill may be unsuitable for you if you have a history of:

• Certain types of migraine

• Heart disease

• Smoking

• Blood clots

There is a risk that endometriosis symptoms will return when you stop taking combined hormonal contraceptives. You might find that different combinations and dosages of estrogen and progestin are more effective in controlling your symptoms, and your doctor can guide you on this.

Progesterone (or progestin)

Progesterone⁵ is a naturally occurring female sex hormone, while progestin is the synthetic version. Taking progestin can effectively treat endometriosis and ease symptoms.

Progestin is especially useful for women who cannot take estrogen-based contraceptives. It can be administered in different ways: pills, injections, or by inserting an intrauterine device or an implant underneath the skin. It is often well tolerated, but can cause mild to severe side effects, including:

• Bloating

• Weight gain

• Irregular or breakthrough bleeding

• Low mood

• Acne

It is not understood exactly how progesterone works to ease endometriosis, but taking it continuously appears to thin endometriosis tissue, prevent growth, and counterbalance the effects of estrogen.

Doctors tend to prescribe progestin as an oral pill first, especially for young women, but this method has disadvantages. An intrauterine device might be preferable because it can be easy to forget to take a pill, and they must be taken at the same time each day.

The levonorgestrel-containing intrauterine system (LNG-IUS) is a T-shaped device that is inserted into the uterus. It contains levonorgestrel (a type of low-dose progestin) that’s released at a constant rate over five years. This method releases progestin straight into the uterus, avoiding any whole-body side effects.

Gonadotropin-releasing hormone agonists (GnRH agonists)

GnRH agonists² treat endometriosis by preventing ovulation. The medication is given via an injection or nasal spray. Research⁵ suggests that GnRH agonists are very effective in reducing endometriosis-related pelvic pain.

GnRH controls the release of two hormones that stimulate the production of estrogen and progesterone in your ovaries: follicle-stimulating hormone (FSH) and luteinizing hormone (LH). GnRH agonists prevent the release of these hormones which stops ovulation and results in “medical menopause.” This prevents endometriosis tissue from breaking down and stops further growth.

Taking GnRH agonists can lead to bone thinning and osteoporosis, so you should only take them for a maximum of six months. Other more common side effects associated with GnRH agonists are similar to menopause symptoms and include:

• Hot flushes

• Vaginal dryness

• Decreased libido

• Irregular mood

GnRH agonists prevent pregnancy, so they are unsuitable for women who want to improve fertility.

Gonadotropin-releasing hormone antagonists (GnRH antagonists)

Research⁷ found that GnRH antagonists (e.g. Elagolix) are as effective as GnRH agonists, but cause fewer side effects.

GnRH antagonists work similarly to GnRH agonists, but they don’t cause an initial flare of FSH and LH hormones. This leads to a quicker decrease in estrogen production. They have similar side effects to GnRH agonists but may be better tolerated⁵ as they are less likely to cause severe hypoestrogenism (estrogen deficiency).

GnRH antagonists are a newer therapy, so they have not been studied as extensively as GnRH agonists in the treatment of endometriosis.

Aromatase inhibitors

When taken with other hormonal therapies like combined hormonal contraceptives and GnRH agonists, aromatase inhibitors⁵ (such as anastrozole, letrozole, and exemestane) can lower endometriosis pain and the volume of endometriosis tissue.

They work by breaking the cycle of aromatase and estrogen in people with endometriosis. Aromatase is an enzyme that leads to estrogen production. Endometriosis tissue overexpresses aromatase, increasing the production of estrogen which is also produced in the ovaries and fat. Estrogen stimulates endometriosis growth and the secretion of prostaglandins (pain and inflammation-causing hormones).

Aromatase inhibitors⁵ block estrogen production in the ovaries and fat, making them particularly helpful for postmenopausal women with endometriosis as fat is their primary source of estrogen.

Long-term use has side effects, including ovarian follicular cysts and bone loss.

Danazol

Danazol⁸, a synthetic androgen (a male sex hormone), can effectively control endometriosis pain by lowering estrogen levels.

Doctors have prescribed danazol to treat endometriosis since the 1970s, but GnRH agonists are now more common.

This hormonal therapy has many side effects. In some women, it causes male characteristics such as increased facial hair and a deeper voice. Other side effects include:

• Weight gain

• Fluid retention

• Bloating

• Acne

• Oily skin

• Irregular bleeding or spotting

• Unstable mood

• Blood clots

Don’t take this medication if you are trying to get pregnant, as it could harm the baby.

Many of these side effects have been observed with oral administration, but studies are being conducted⁵ about other methods, such as a vaginal ring or intrauterine device.

How to find the right hormonal therapy for you

All of these hormonal therapies have been shown to effectively treat endometriosis and reduce symptoms, but you and your doctor should also consider side effects when selecting a treatment.

While these hormonal therapies can offer great results, you might relapse when you stop taking them. What’s more, some are unsuitable for long-term use and many prevent pregnancy. If you have a high risk of stroke or blood clots, your doctor will probably recommend you take a progesterone-only therapy. Estrogen-based therapies may increase your risk.

Whether you want to avoid or enable pregnancy is another consideration. Some hormonal therapies used to treat endometriosis prevent pregnancy, while others don’t provide effective birth control.

Discuss different options with your doctor, as they can prescribe the best therapy while considering side effects, health risks, and fertility.

The lowdown

Hormonal therapies can help manage the symptoms of endometriosis, including pelvic pain. They may be prescribed if pain-relieving medications (such as acetaminophen and NSAIDs) or alternative therapies haven’t worked.

Hormonal therapies work in different ways, but their general goal is to decrease estrogen production as this stimulates endometrial growth. Deciding which hormonal therapy to take can be confusing as they all have different side effects, including pregnancy prevention. Talk to your doctor who can prescribe the best hormonal therapy for you.