Endometriosis Treatment: Medicines, Mirena and Surgery

Endometriosis treatment aims to stop menstruation, because when the periods stop, endometrial tissue outside the uterus regresses. Most women start with combined oral contraceptive pills or a progestogen, move to a hormonal intrauterine device or GnRH-based drugs if needed, and have minimally invasive surgery when medicines fail, a cyst is large or a pregnancy cannot wait.

Dr. Tripti Sharan, Senior Director - Obstetrics & Gynaecology and Head – High Risk Pregnancy, BLK-Max Super Speciality Hospital, New Delhi, India, where her department performs laparoscopic, robotic and open surgery, is clear that the operation is not the default. "It is not always surgical, and not every case needs to be treated," she told her masterclass audience. This article sets out her treatment ladder: who needs treatment, which medicines to use and in what order, when to operate, and how to prevent the disease coming back. The complete guide to endometriosis covers causes, and the diagnosis article covers symptoms and tests.

Who needs endometriosis treatment

Endometriosis is sometimes found by chance on an ultrasound in a woman with no symptoms. Such women do not need treatment; they can be observed with periodic ultrasound. Treatment becomes necessary when the disease causes symptoms, chiefly pain or abnormal bleeding, or when it contributes to infertility.

The choice between medicine, minimally invasive surgery and open surgery then depends on the patient's profile: her symptoms, the size and site of the lesions, her age and whether she wants to conceive.

The principle behind medical treatment

Endometriotic tissue grows under the influence of oestrogen and bleeds with each cycle. Every hormonal treatment for endometriosis works by suppressing that cycle: no ovulation, no menstruation, and the deposits outside the uterus gradually shrink and "burn out". The same logic explains why the disease improves during pregnancy, when there are nine months without periods, and why it usually subsides after menopause.

Dr. Sharan noted that clinicians often describe pregnancy as the best treatment for that reason. Current European guidance (ESHRE, 2022) advises against recommending pregnancy as a treatment in itself, and symptoms often return after delivery; pregnancy relieves the disease while it lasts but is not a substitute for a treatment plan.

Combined oral contraceptive pills

Combined oral contraceptive pills (COCPs) are, in Dr. Sharan's words, "a very, very good drug" for endometriosis, especially in young women who do not want a pregnancy. Taken conventionally, the pill produces a withdrawal bleed when it is stopped after 21 days. To stop periods altogether, Dr. Sharan often prescribes the pill continuously for three months, then allows a short break, so that the number of periods is reduced and the lesions can heal.

For women who have completed their family, the pill is her preferred long-term option, ahead of GnRH drugs. It does not cause hot flushes, provides hormonal support and suppresses the endometrial glands, so "oral contraceptive pills is an ideal way to go forward in a woman who has completed her family."

Progestogens

Progestogens counter the effect of oestrogen on the endometrium and suppress ovulation, so ectopic endometrial tissue also regresses. Options Dr. Sharan described include micronised progesterone, dydrogesterone and dienogest. Dienogest causes amenorrhoea, an absence of periods, and Dr. Sharan uses it to stop periods for five or six months at a time. Micronised progesterone and dydrogesterone have a particular advantage for women trying to conceive, discussed in the fertility article.

The hormonal intrauterine device (Mirena)

The levonorgestrel intrauterine system, widely known by the brand name Mirena, is a small progestogen-releasing device placed inside the uterus, similar in shape to the copper T used for contraception. It releases hormone locally for five years, so the patient needs no daily tablet. The endometrial glands atrophy, bleeding stops, and endometriosis elsewhere in the pelvis, on the ovaries, tubes, bowel or bladder, regresses as well.

Its limitation is that a woman cannot conceive while it is in place. Dr. Sharan therefore reserves it for women who have completed their family and whose cysts are not large; endometriotic cysts bigger than 5 or 6 centimetres need to be removed rather than treated with a device.

GnRH agonists and antagonists

Gonadotrophin-releasing hormone (GnRH) drugs switch off the ovaries' hormone production through the pituitary gland, creating a temporary, reversible medical menopause.

• Injectable GnRH agonists, such as leuprolide, are given monthly or three-monthly. Dr. Sharan generally uses them for about six months, often for women who are poor candidates for surgery or who want to preserve their fertility. A woman cannot conceive while taking them; the disease regresses during treatment, although suppression has not been shown to improve the chance of conception after it stops.
• Oral GnRH antagonists, such as elagolix, are a newer class taken by mouth. Dr. Sharan described them as working "wonderfully" and as safe to use for one to two years. Licensed duration depends on the dose: in the United States, elagolix is approved for up to 24 months at the lower dose and up to 6 months at the higher dose.

The main drawback of GnRH drugs is menopausal symptoms, particularly hot flushes. Because they lower oestrogen, prolonged use also affects bone density.

Aromatase inhibitors, danazol and mifepristone

• Aromatase inhibitors such as letrozole and anastrozole reduce oestrogen levels and are an emerging option. Whenever oestrogen is suppressed for a long time, Dr. Sharan gives calcium and vitamin D to protect the bones.
• Danazol was used historically but has many undesirable side effects. Dr. Sharan has never used it and it is now rarely prescribed.
• Mifepristone (RU-486) has been tried but is not commonly used.

Start low and escalate

Dr. Sharan's closing advice to the doctors in the session was about sequence. Some patients respond best to the pill, some to a Mirena, some to an oral GnRH antagonist, and nobody can predict which in advance. Her rule is to begin with the commonest, most widely used drug and move to stronger treatment only when needed, "because if you start from the top, then you cannot go down."

When endometriosis needs surgery

Medicines act well on the normal endometrium inside the uterus, but the ectopic tissue outside it is sometimes unresponsive. Dr. Sharan's indications for surgery are:

• Failed medical treatment, with symptoms that persist despite adequate therapy.
• Infertility, particularly when the woman needs to conceive and does not have one or two years to wait for medicines to work.
• A large chocolate cyst. Her threshold for removing an endometrioma is about 5 centimetres; smaller lesions can be treated in other ways.
• Severe pain from adhesions, which must be divided to relieve it.

Laparoscopic and robotic surgery for endometriosis

Most endometriosis surgery today is minimally invasive, performed laparoscopically or with robotic assistance. The surgeon inspects the whole pelvis and treats what is found:

• Cystectomy: large endometriomas are removed. (See the cost of ovarian cystectomy.)
• Ablation: smaller lesions are destroyed by diathermy (electrical cauterisation) or with a CO2 laser.
• Adhesiolysis: adhesions are divided to free the tubes and ovaries and relieve pain.

Dr. Sharan also described LUNA, laparoscopic uterosacral nerve ablation, in which the nerves running in the uterosacral ligaments are destroyed to relieve pain. Randomised trials have not shown a benefit for endometriosis-related pain, and current European guidance (ESHRE, 2022) recommends against it.

Deep infiltrating endometriosis carries the highest surgical risk because it grows into the bowel, ureters and other structures, and removing it can injure them. When bowel disease is present, Dr. Sharan advises having the gastrointestinal surgical team on standby. Bowel endometriosis left untreated causes painful bowel movements and adhesions that contribute to infertility, so the decision to operate is a balance of these risks.

Open surgery and definitive surgery

Open surgery (laparotomy) is now uncommon. Dr. Sharan reserves it for very large lesions, disease that has not responded to minimally invasive surgery, and repeated recurrence where medical therapy has failed.

For women with repeated recurrence, removal of both ovaries and tubes, and sometimes the uterus when adhesions are extensive, may be considered. This is reserved for women who have completed their family and are older. Performed at a young age, it brings on menopause, and in a woman who has not completed her family it is not an option.

Combining medicine and surgery

Dr. Sharan often combines the two. Three months of a GnRH agonist such as leuprolide, or of contraceptive pills, before surgery shrinks the lesions and makes them less vascular and less adherent, so the operation is easier.

After conservative surgery, in which the cyst and adhesions are removed but the uterus and ovaries are kept, medical treatment continues to prevent recurrence. "Endometriosis is a tendency," she said: removing a cyst does not remove the tendency, and new cysts can form. Prophylaxis can be with contraceptive pills, GnRH agonist injections or a Mirena.

Timing procedures around the cycle

Dr. Sharan schedules procedures such as hysterosalpingography (HSG, the dye test of tubal patency) in the days just after a period and avoids the days before one. Pushing dye through the uterus when the endometrium is thick risks carrying endometrial tissue through the tubes into the abdomen, where it can form new endometriosis. She schedules surgery in the same post-menstrual window, when there is less bleeding and less chance of seeding new disease.

The audience's questions on Mirena, long-term contraceptive pills and bowel complications are answered in full in the Live Discussion.