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Gonadotrophin‐releasing hormone analogues for pain associated with endometriosis

 Endometriosis is a common condition affecting women of child‐bearing age, and is usually due to the presence of endometrial tissue in places other than the uterus. Common symptoms include pain and infertility. GnRHas are a group of drugs often used to treat endometriosis by decreasing hormone levels. This review found evidence to suggest treatment with a GnRHa improved symptom relief compared with no treatment or placebo. There was no evidence of a statistically significant difference when compared with danazol or intra‐uterine progestagen. However, there more side effects in the GnRHa group compared with the danazol group. There is not enough evidence to make clear if higher or lower doses of GnRHa are better, or which length of treatment is best.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2011

Danazol for pelvic pain associated with endometriosis

Danazol reduces the painful symptoms of endometriosis but has androgenic effects. Endometriosis is a painful condition where endometrial tissue grows outside the uterus. It can cause cysts and infertility. Danazol is a hormone that produces male characteristics as well as weight gain and acne. It does, however, relieve the painful symptoms of endometriosis, although the side effects can be unacceptable. The improvement was still present six months after treatment was stopped. There was some evidence that women who took danazol were satisfied with the treatment compared with women who had inactive treatment.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2010

The causes of endometriosis

In endometriosis, the kind of tissue that lines the womb (endometrial tissue) also grows outside the womb. It is still not clear why this happens. There are various theories about what causes endometriosis. Several factors probably play a role.The inside walls of the womb (uterus) are completely lined with mucous membranes known as the endometrium. These are different to other mucous membranes in the body, particularly in their ability to change: Once a month, during each menstrual cycle, their cells multiply and the lining becomes thicker so that it can nourish a fertilized egg if necessary. If fertilization does not take place and the woman does not become pregnant, most of the thick membrane tissue which has built up is shed and leaves her body during her period. The process of building up and shedding the lining of the womb is regulated by the female sex hormones estrogen and progesterone.Illustration: Womb without endometriosis - as described in the articleEffect of hormones on the lining of the womb (uterus) during a menstrual cycle Illustration: Effect of hormones on the lining of the womb (uterus) during a menstrual cycleIn endometriosis, the kind of tissue that normally lines the womb also grows in other parts of the body. Medically speaking, there are different types of endometriosis, depending on where the endometrial tissue grows.In the muscles of the womb or in the wall of a Fallopian tube, where the tissue is attached to the lining of the womb (common);in the pelvic area, including the ovaries, Fallopian tubes and the “Pouch of Douglas” found between the womb and rectum at the end of the bowel (common);outside the pelvic area, for instance in the bladder or bowel (rare), and very rarely in parts of the body that are further away, like the lungs.Every month during the menstrual cycle, the mucous membrane tissue in endometrial implants outside of the womb is built up and shed. But because the blood and shed tissue cannot leave the woman’s body through her vagina, they stay near the endometrial area. Here they can lead to inflammations, which in turn can cause scars and adhesions to develop.Illustration: Womb with endometrial implants, as decribed in the text

Informed Health Online [Internet] - Institute for Quality and Efficiency in Health Care (IQWiG).

Version: May 7, 2014

There is no evidence that hormonal suppression either before or after surgery for endometriosis is associated with a benefit

Endometriosis is caused by the lining of the uterus (endometrium) spreading outside the uterus. It can cause pelvic pain, painful periods and infertility. Common treatments are hormonal suppression with medical therapy to reduce the size of endometrial implants or laparoscopic surgery (where small incisions are made in the abdomen) to remove visible areas of endometriosis. There is no evidence that hormonal suppression either before or after surgery is associated with a benefit compared with surgery alone.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2011

Endometriosis: Surgery: What are the advantages and disadvantages of additional hormone therapy?

There is no proof that taking hormonal medication before or after endometriosis surgery improves the outcome of the treatment. But hormone products such as GnRH analogues do often have side effects and reduce fertility during treatment.

Informed Health Online [Internet] - Institute for Quality and Efficiency in Health Care (IQWiG).

Version: May 7, 2014

Interventions for women with endometrioma prior to assisted reproductive technology

Endometriomata are a form of ovarian endometriosis, classified as cysts within the ovaries. They are a common cause of subfertility and pelvic pain. This review aimed to determine which treatment approach was better for women with subfertility and endometriomata who were undergoing assisted reproductive technology (ART). Four trials were identified. A gonadotropin‐releasing hormone (GnRH) agonist showed a positive treatment effect on the ovarian response to controlled ovarian hyperstimulation (COH) and the number of mature oocytes retrieved compared to GnRH antagonist. The evidence for surgery was limited but aspiration was associated with a greater ovarian response than expectant management (a wait and see approach). Further randomised controlled trials of interventions for the management of endometrioma in women undergoing ART are required.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2012

Ovulation suppression for endometriosis

This review of 23 trials involving 3043 women with endometriosis has shown that there no evidence of benefit with the use of ovulation suppression for women with endometriosis and infertility. Endometriosis is caused by the lining of the uterus (endometrium) spreading to a site outside the uterus. It is associated with subfertility and can cause pain during both sexual intercourse and menstruation. The hormone oestrogen stimulates the growth of endometriosis. For many years, the use of drugs such as danazol to stop ovulation and the production of oestrogen has been standard practice in the treatment of pain and subfertility caused by endometriosis. This works well for pain, but does not appear to improve fertility. In fact, as ovulation and periods are stopped for the time of treatment, fertility may be reduced by this approach.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2009

Modern combined oral contraceptives for treatment of pain associated with endometriosis

Endometriosis is a common women's healthcare condition which is defined as the growth of endometrium (lining of the uterus) at sites outside the uterus, such as the ovaries. Endometriosis is commonly found in women with painful periods, pain with sexual intercourse, pelvic pain and infertility. Hormonal treatments, including the oral contraceptive pill (OCP) and gonadotrophin releasing hormone (GnRH) analogues are used to relieve the pain symptoms associated with endometriosis. There is some evidence to suggest that such treatments may also treat the actual deposits of endometriosis. However, many of the hormonal treatments have side effects which limit their acceptability and duration of use. Surgery may also be used to remove the deposits.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2009

Testing for endometriosis

Endometriosis is often only diagnosed and treated late. If you are thought to have endometriosis it is important to decide what examinations are actually needed. More invasive procedures such as an examination of the inside of your abdomen (laparoscopy) are not always necessary to help decide how to best treat the symptoms, and they are associated with risks.In endometriosis, the lining of the womb (endometrium) also grows outside the womb. This endometrial tissue is benign (non-cancerous) and does not always cause noticeable pain. Endometriosis often first becomes noticeable if it causes considerable pain, if the tissue sticks together and adhesions form, or if it makes it difficult to get pregnant.Severe period pain, pain during or after sex and tenderness in parts of the pelvis are all typical signs of endometriosis.

Informed Health Online [Internet] - Institute for Quality and Efficiency in Health Care (IQWiG).

Version: May 7, 2014

Use of a levonorgestrel‐releasing intrauterine device (LNG‐IUD) for recurrence of symptoms in women who have had surgery for endometriosis

Endometriosis is the presence of endometrial tissue outside the uterus, usually in the pelvis, that can lead to infertility and pelvic pain. It is managed with surgery, hormonal medications, or a combination of both. The progestogen levonorgestrel is one such hormonal medication. The aim of this review was to assess whether the use of a hormone‐releasing intrauterine device was beneficial for managing associated painful symptoms and for preventing recurrence of endometriosis following surgery. Although preliminary findings are encouraging, at this stage there is only limited evidence from three randomised trials of a beneficial role with the use of the LNG‐IUD in reducing the recurrence of painful periods following surgery for endometriosis. The strength of the evidence was graded as moderate reflecting our belief that future evidence will most likely not change these findings.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2013

Chinese herbs for endometriosis

Endometriosis is a common gynaecological condition causing menstrual and pelvic pain. Treatment involves surgery and hormonal drugs, with potentially unpleasant side effects and high rates of reoccurrence of endometriosis. This review suggests that Chinese herbal medicine (CHM) may be useful in relieving endometriosis‐related pain with fewer side effects than experienced with conventional treatment. However, the two trials included in this review are of poor methodological quality so these findings must be interpreted cautiously. Better quality randomised controlled trials are needed to investigate a possible role for CHM in the treatment of endometriosis.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2012

Endometriosis: Overview

Endometriosis? Never heard of it. Many people say so, even though endometriosis is one of the most common medical conditions affecting the lower abdomen (lower belly) in women. Some women are not even aware they have endometriosis, others experience severe pain every month for several days. Read about the causes, effects, typical symptoms are treatment options.

Informed Health Online [Internet] - Institute for Quality and Efficiency in Health Care (IQWiG).

Version: May 7, 2014

Endometriosis symptoms

Endometriosis causes serious pain and cramps in some women, while others only have a little discomfort or notice nothing at all. Women usually have endometriosis symptoms during their menstrual period, but may also experience them at other times. The severity of symptoms does not always depend on things like the extent of endometrial tissue growth a woman has in her body.Endometriosis is a condition where the kind of tissue that normally lines the womb (endometrial tissue) grows in other parts of a woman’s body too. These “growths” are known as endometrial implants. They do not always cause pain. Endometriosis can lead to various symptoms, depending on things like how many endometrial implants a woman has, and where they are in her body. The most common symptoms are:Very painful menstrual periods (dysmenorrhea): When a woman has her period (menstruation), the muscles in the wall of her womb repeatedly tighten and squeeze in order to shed the lining of the womb. This can cause period pain. Women who have endometriosis may have particularly severe pain and cramping during their period. Many girls and women think this is normal because things have always been that way for them. It never crosses their mind that their severe period pain might be caused by a medical condition like endometriosis.Pain during sex (dyspareunia): This pain is usually described as burning or cramp-like pain. Sometimes women only feel it after they have finished having sex.Abdominal (lower belly) pain: Various degrees of pain may be felt in different parts of the abdomen, sometimes radiating to the back or legs. The pain is not necessarily associated with women’s menstrual period. Permanent (chronic) abdominal pain tends to be rare.Gastrointestinal (stomach and bowel) problems: If endometriosis affects a woman’s bowel, she might feel full or have painful bowel movements. If it affects her bladder, passing urine might hurt.General exhaustion: Severe and frequent endometriosis symptoms often lead to general exhaustion. This makes women less able to cope with physical and mental strain.All of these symptoms can be caused by other things too, so endometriosis cannot be clearly diagnosed based on these symptoms alone.

Informed Health Online [Internet] - Institute for Quality and Efficiency in Health Care (IQWiG).

Version: May 7, 2014

Hormone therapy for women with endometriosis and surgical menopause

Endometriosis is known to result in variable severity of symptoms. For some women bilateral removal of the ovaries (oophorectomy) with or without an hysterectomy may be required to manage symptoms. This brings women into premature menopause. It is thought that hormone replacement therapy may enhance the recurrence of the disease due to its effect on the remaining endometriotic deposits in the pelvis. Only two small randomised controlled were identified in the literature that looked at this problem. Further research is required to clarify the effect of different hormone replacement therapy types on the recurrence of the disease and the associated pain including during sex.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2010

Pentoxifylline for premenopausal subfertile women with endometriosis

Endometriosis is a painful condition where endometrial tissue grows outside the uterus, which potentially affects a woman's ability to conceive. Recent studies support the influence of the immune system on this disease. Pentoxifylline is an immunomodulator drug (used for effects on the immune system) which may relieve the symptoms of the disease without inhibiting ovulation. It may improve blood flow through blood vessels and, therefore, help with blood circulation because of its anti‐inflammatory activity. However, this systematic review of four trials found there was not enough evidence upon which to draw conclusions about the effectiveness and safety of pentoxifylline in terms of fertility and pain relief outcomes in women with endometriosis. At this update in 2011, there was still no evidence of an increase in pregnancy events in the pentoxifylline group compared with placebo.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2012

Progestagens and anti‐progestagens for pain associated with endometriosis

Endometriosis is a painful condition where tissue from the lining of the womb (uterus) is found outside the uterus as well. It can cause pain in the abdomen, generally and during periods (menstruation) or sex. Endometriosis can also lead to infertility. Treatments include surgery or drugs to try and shrink the tissue. Progestagens and anti‐progestagens are some of the hormonal drugs used for treatment. This systematic review of trials found limited evidence for the effectiveness of these drugs in the reduction of pain from endometriosis. This was due to the limited number of randomised controlled trials comparing each drug.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2012

Acupuncture for pain in endometriosis

Endometriosis is a gynaecological disease that causes chronic pelvic pain, most notably painful menstruation, as the most common complaint. Acupuncture is frequently used to treat both pain and various gynaecological conditions. This review examined the effectiveness of acupuncture for reducing pain in endometriosis; however only one study met our inclusion criteria. The data from the included study, involving 67 women, indicated that ear acupuncture is more effective compared to Chinese herbal medicine for reducing menstrual pain. The study did not report whether participants suffered any side effects from their treatments. Larger, well‐designed studies comparing acupuncture with conventional therapies are necessary to confirm these results. 

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2011

Long‐term pituitary down‐regulation before in vitro fertilization (IVF) for women with endometriosis

Endometriosis is a disease characterised by the presence of endometrial tissue (the lining of the womb) outside the cavity of the womb. Many women with the disease suffer from menstrual pain and some suffer from infertility. Infertile women with endometriosis are often treated with in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) but have a lower chance of becoming pregnant compared to women who are infertile with blocked tubes. It has been suggested that giving GnRH agonists before IVF or ICSI could increase the chances of pregnancy. We have reviewed the literature and found that treating women for three to six months with GnRH agonists before IVF or ICSI increases the odds of clinical pregnancy four‐fold. However, at present there is no information on the effect of this treatment on the incidence of ectopic pregnancy, multiple pregnancies or complications arising for the women or their offspring.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2010

My partner has endometriosis – what does that mean for me?

Having a partner who suffers from severe abdominal pain on several days every month will affect your life together too. It is not easy to deal with. If this pain is caused by endometriosis, effective relief is often available. But it is important to be aware of the options, limitations and disadvantages of treatments.Men sometimes find it hard to understand how their partner’s period pain can be so bad that they regularly have to cancel plans. Perhaps you have also found yourself wondering why your partner cannot simply cope with her period pain “like other women do.”The answer is easy: If your partner has endometriosis, she is in no way just being oversensitive or “whinier” than other women. Endometriosis is a medical condition where the kind of tissue that usually lines the womb also grows in other parts of the body. These “growths” are called endometrial implants, and may be small or larger in size. Like the lining of the womb, they build up and are shed every month. But, unlike period (menstrual) blood, the tissue that is shed in the abdomen cannot leave the body, so inflammations and scars often develop.About 1 out of 10 women have endometriosis. Whether or not it causes symptoms, and what kind of symptoms women have, depends on things like where the endometrial implants are and how bad the inflammations are. Some women hardly have any symptoms, whereas others are regularly knocked out of action by painful cramping. Endometrial implants may grow on a woman’s ovaries and in her Fallopian tubes, which can lead to fertility problems. Sometimes women first find out that they have endometriosis when they go to the doctor because they have not been able to get pregnant despite trying for a long time.

Informed Health Online [Internet] - Institute for Quality and Efficiency in Health Care (IQWiG).

Version: May 7, 2014

Both hormone replacement therapy and danazol stop the loss of bone density that occurs when women take gonadotrophin‐releasing hormone analogues for endometriosis

Endometriosis is a painful condition caused where tissue from the lining of the uterus (womb) is outside the uterus as well. It can be treated with gonadotrophin‐releasing hormone analogues (GnRHas). Possible adverse effects of GnRHas include loss of bone density, loss of sex‐drive and hot flushes. The decrease in bone density is particularly important because it increases the risk of osteoporosis. The review found that taking hormone replacement therapy with GnRHas can prevent this adverse effect. Danazol can also prevent loss of bone density, but adverse effects of danazol can include acne, weight gain and headaches.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2010

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