Endometriosis: hormonal treatments and pain relief

Why hormonal treatment for endometriosis?

Endometriosis lesions respond to the hormones of the cycle, particularly oestrogens. With each cycle, they become inflamed and bleed, which sustains the pain. Hormonal treatments aim to:

• suppress periods or make them less frequent;
• reduce the stimulation of the lesions by oestrogens;
• reduce inflammation and therefore pain.

These treatments relieve symptoms but do not make the disease disappear: symptoms may return when they are stopped. They are therefore designed to be taken over the long term, for as long as they are effective and well tolerated. As they are contraceptive or block ovulation, they are not suitable when trying for a baby.

Treatment can be started on the basis of clinical and imaging findings, without waiting for surgical confirmation.

What are the first-line treatments?

The combined oestrogen-progestogen pill

The combined pill (oestrogen + progestogen) is one of the two first-line treatments. In the case of painful periods, the French guidelines advise taking it continuously, i.e. without a break between packs, to suppress periods. Irregular bleeding may occur in the first few months; it often decreases over time.

Its contraindications are those of any combined oestrogen-progestogen contraception: history of deep vein thrombosis or embolism, migraine with aura, smoking after 35, certain cardiovascular diseases. These are checked before prescribing.

The 52 mg levonorgestrel hormonal IUD

The levonorgestrel intrauterine device (IUD) releases a progestogen directly into the uterus for several years. It reduces the heaviness and pain of periods. It is useful in the case of associated adenomyosis or a contraindication to oestrogens. The French guidelines place it on the same level as the pill, both before and after surgery.

What are the second-line treatments?

If effectiveness is insufficient, or in the case of side effects or contraindications, other treatments are offered.

Progestogens

Progestogens put the lining of the uterus and the lesions at rest. The 2025 Cochrane review concludes that oral progestogens probably reduce overall pain and painful periods compared with placebo, and improve quality of life. Compared with the pill or GnRH agonists, differences in effectiveness are small or uncertain; the choice is made mainly on tolerability.

GnRH agonists with add-back therapy

These medicines put the ovaries at rest and create a temporary and reversible state of menopause. They are effective against pain but cause hot flushes, vaginal dryness and loss of bone density. The French guidelines require them to be combined with an "add-back therapy" containing an oestrogen, which limits bone loss and improves quality of life, introduced before the third month.

The 2023 Cochrane review of these treatments (72 studies) finds a possible reduction in pain compared with placebo, but with a low level of evidence, and confirms the bone loss. They are not recommended as first-line treatment in adolescents, because of the risk to bone mass that is still developing.

Oral GnRH antagonists

More recent molecules, taken orally, directly block the hormonal axis. Combined with add-back therapy, some have been authorised in Europe for endometriosis. Their precise place in the French strategy remains to be defined; they may be discussed if the usual treatments fail.

Which painkillers should be used?

Non-steroidal anti-inflammatory drugs (ibuprofen, naproxen, etc.) are often used during periods. They can relieve painful periods but do not treat the disease, and their specific effectiveness in endometriosis is poorly demonstrated. They should be taken judiciously because of digestive and kidney risks. In pregnancy, they must not be used from the 6th month, even as a single dose or as a gel, and before then only if prescribed by a doctor (see medicines in pregnancy).

Paracetamol can be combined with them. Opioid painkillers are not a long-term treatment for endometriosis: their prolonged use exposes patients to dependence and to heightened sensitivity to pain.

What can be done when pain persists despite treatment?

Endometriosis pain does not depend only on the lesions. Over time, the nervous system can become more sensitive (this is called sensitisation), and muscular pain in the perineum, back or bladder may be added. The French guidelines state that chronic pain justifies a multidisciplinary assessment. Referral to a specialist pain clinic may then be offered.

Depending on the situation, the following may be offered:

• a reassessment of the diagnosis by second-line ultrasound or MRI;
• a change of hormonal treatment;
• care in a pain centre;
• pelvic floor physiotherapy, particularly in the case of contracture of the perineal muscles;
• complementary approaches (yoga, relaxation, osteopathy), which may improve quality of life without acting on the lesions;
• surgery, discussed at a multidisciplinary team meeting (see Endometriosis surgery).

What is the role of treatment after surgery?

After an operation for endometriosis, and in the absence of an immediate plan for pregnancy, the French guidelines recommend hormonal treatment to reduce the risk of pain recurring: combined oestrogen-progestogen pill or 52 mg levonorgestrel IUD as first line. After surgery for an endometrioma, the pill is recommended to reduce the risk of the cyst recurring; GnRH agonists are not recommended for this purpose alone.

Conversely, hormonal treatment before surgery is not recommended solely to make the operation easier or reduce complications.

How is follow-up organised?

A reassessment consultation is useful a few months after starting a treatment to judge its effectiveness and tolerability.

It is not necessary to repeat imaging systematically if symptoms are controlled. New imaging is discussed if pain returns, if digestive or urinary symptoms appear, or to monitor an endometrioma.

Frequently asked questions

General information article: it does not replace a medical consultation. In an emergency, call 15 or 112 in France, or your local emergency number.