Progestins as a treatment for endometriosis

by Ros Wood

Progestins are a group of drugs that behave like the female hormone progesterone. They have been used since the mid 1950s to treat the symptoms of endometriosis [1]. They are also sometimes referred to as gestogens, progestogens or progestagens.

Progestins come in different forms, each of which has its own advantages and disadvantages. The names, forms and dosages most commonly used for women with endometriosis are outlined in the table below. There is no evidence at the moment that any particular progestin is preferable to another [2].

The progestins are effective treatments for the symptoms of endometriosis. However, like all the hormonal drugs used for endometriosis, they have side effects, which some women find intolerable. They are safer and cheaper than the GnRH-agonists and danazol, which some gynaecologists believe makes them appropriate for women who need prolonged or repeated treatments [3].

The usual length of treatment is 3–6 months [2], but longer courses may be recommended, and repeat courses are common. The levonorgestrel intrauterine system can remain in the uterus for up to 5 years.

The dosages most commonly used for endometriosis are shown below. However, endometriosis pain is usually only relieved when there is no menstrual bleeding, so the most appropriate dose for you will usually be the minimum dose needed to stop your periods [5].

The side effects experienced and their severity vary from progestin to progestin depending on their chemical nature and the dosage used. Nevertheless, women usually experience fewer side effects with progestin treatment than with GnRH-agonist or danazol treatment [2]. Most women will experience at least one or two mild to moderate side effects, and some may experience several. Reducing the dosage to the minimum needed to suppress menstruation will often minimise the side effects.

The side effects are not usually serious medically [6], but can be unpleasant and difficult to live with. Some women cannot complete a course of treatment, because they find them intolerable [7].

The main side effects are acne, bloating, breakthrough bleeding, breast discomfort, depression, dizziness, fluid retention, headaches, irregular bleeding, lethargy, moodiness, nausea, prolonged bleeding, spotting, vomiting and weight gain [2,5,8]. If you suspect you may be experiencing other side effects, talk to your doctor.

Heavy irregular bleeding and spotting can usually be overcome by increasing the dose until the bleeding stops [5]. Breakthrough bleeding can usually be overcome by taking oestrogen for 7 days [2].

The levonorgesterel intrauterine system is sometimes expelled by the uterus, particularly in the first year [9]. Infrequently, it may perforate (penetrate through) the uterus (particularly if inserted within 6 weeks of a vaginal birth, or 12 weeks of a caesarian birth), or lead to a pelvic infection (especially in the first 3 weeks after insertion) [9].

The side effects of progestins are reversible. With the exception of depot medroxyprogesterone acetate, the side effects usually disappear soon after completing treatment. The side effects of depot medroxyprogesterone disappear soon after the drug has been eliminated from the body, which may take weeks or months depending on the dosage used and the body’s ability to metabolise the drug.

There are no known long-term side effects of progestin treatment.

Little research has been conducted into the effectiveness of the progestins for the treatment of endometriosis [10]. Nevertheless, the results of clinical trials conducted to date suggest that the different progestins are equally effective [2], and that when taken continuously (every day) they relieve endometriosis-associated pain as effectively as the other hormonal drugs [2,8,10]. However, they are not usually effective when taken only during the luteal phase (second half) of the menstrual cycle [10].
The progestins control pain symptoms in approximately 3 out of 4 women [4]. However, they may not relieve symptoms completely [7].

Symptoms often recur following treatment [7]. The recurrence of symptoms may occur months or years after treatment ceases.

Like all the hormonal drugs used for endometriosis, the way women respond to progestins varies widely, and the way an individual woman responds to the different progestins may also vary. It is impossible to predict how you will respond to a particular progestin, so a process of trial and error may be needed to find one that works for you.

Use before surgery

There is no evidence to justify using a course of hormonal drug treatment as a preparation for surgery [11].

Use after surgery

There is some evidence to justify using hormonal drug treatments following surgery to suppress the growth and development of any remaining or new endometrial implants [11,12].

Use in recurrent endometriosis

Repeat courses of progestins may be used for women with recurrent endometriosis.

Some gynaecologists recommend that women with chronic endometriosis take progestins long term to keep their pain under control, and avoid the roller-coaster ride of pain recurring every time they stop treatment. In these situations, it is important to take only the minimum dose needed to stop your periods. If taking progestins for many years, there is a possibility of thinning of the bones due to a lack of oestrogen, so talk to your doctor about having a bone density scan periodically to check your bone density.

None of the progestins — like all the hormonal treatments for endometriosis — will improve your chances of conceiving, so they should not be used as a treatment for infertility [8].

About 6–8 weeks after starting treatment, you should visit your gynaecologist to discuss how the treatment is progressing. Contact your gynaecologist if you develop any problems between scheduled visits.

If there is any possibility that you may be pregnant, you should not start or continue treatment with a progestin, as progestins can cause abnormalities in the developing foetus. You should also use non-hormonal barrier contraception (for example, condom or diaphragm or both) during treatment [9].

The use of progestins while breastfeeding is not recommended. Small amounts of progestins have been found in the milk of mothers taking them, and the effect on the infant is not known.

1. Kistner R W. The use of newer progestins in the treatment of endometriosis. Am J Obstet Gynecol 1958;75:264–278.

2. Kennedy S, Bergqvist A, Chapron C, D'Hooghe T, Dunselman G, Greb R, Hummelshoj L, Prentice A, Saridogan E. ESHRE guideline for the diagnosis and management of endometriosis. Human Reprod 2005;20(10):2698-2704.

3. Schweppe K-W. Current place of progestins in the treatment of endometriosis-related complaints. Gynecol Endocrinol 2001;15(S6):22–8.

4. Vercellini P, Fedele L, Pietropaolo G, Frontino G, Somigliana E, Corsignani PG. Progestogens for endometriosis: forward to the past. Hum Reprod Update 2003;9:387–96.

5. Kennedy S. The patient’s essential guide to endometriosis. United Kingdom: Alden, 2003.

6. Winkel CA, Scialli AR. Medical and surgical therapies for pain associated with endometriosis. J Womens Health Gend Based Med 2001;10:137–62.

7. Royal College of Obstetricians and Gynaecologists. Clinical green-top guidelines: the investigation and management of endometriosis. RCOG, 2000.

8. Hughes E, Fedorkow D, Collins J, Vandekerckhove P. Ovulation suppression for endometriosis. The Cochrane Database of Systematic Reviews 2003, Issue 3. Art. No.: CD000155.

9. Australian Medicines Handbook Pty Ltd. Australian Medicines Handbook 2005. Adelaide: Australian Medicines Handbook Pty Ltd, 2005.

10. Prentice A, Deary AJ, Bland E. Progestagens and anti-progestagens for pain associated with endometriosis. The Cochrane Database of Systematic Reviews 2000, Issue 2. Art. No.: CD002122.

11. Vercellini P, Frontino G, De Giorgi O, Pietropaol G, Pasin R, Crosignani PG. Endometriosis: preoperative and postoperative medical treatment. Obstet Gynecol Clin North Am 2003;30:163–80.

12. Gambone JC, Mittman BS, Munro MG, Scialli AR, Winkel CA. Consensus statement for the management of chronic pelvic pain and endometriosis: proceedings of an expert-panel consensus process. Fertil Steril 2002;78:961–72.

Paolo Vercellini, Associate Professor, University of Milano, Italy
Martin Sillem, Doctor Med, DRK Krankenhaus Neuwied, Germany