Adenomyosis Medication

When symptoms are severe, these medical therapies are usually used as a short-term fix while a long-term solution is being organised.

Pain-relieving medications

Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to be effective in reducing period pain. Examples include ibuprofen (Nurofen), mefenamic acid (Ponstan), naproxen (Naprogesic), and diclofenac (Voltaren). These drugs work by blocking prostaglandin production and can reduce uterine cramps. They also have a mild effect on reducing the heaviness of menstrual bleeding. However, none of these drugs have been tested specifically for effectiveness in the setting of adenomyosis.

NSAIDs are over-the-counter medications, and they’re generally safe. Common side effects are stomach upset with pain, nausea, and heartburn. Some people can develop bleeding ulcers in the stomach and duodenum (the first part of the small bowel). Also, blood pressure might be raised, and asthma triggered. Serious rare side effects have been reported, including kidney failure, and even heart attacks and stroke. There’s no evidence to determine which one is more effective or safer.

Menstrual-flow-reducing medication:

Tranexamic acid (Cyklokapron) has been shown to be effective in reducing heavy menstrual bleeding. It works by slowing down the breakdown of clots that are formed by the body to stop bleeding. Clot formation and breakdown is a dynamic process. Tranexamic acid shifts the balance towards thrombosis by slowing the breakdown of clots, so they last longer. It’s also used in trauma, post-partum haemorrhage, and during surgery.

Side effects from this medication are rare but include nausea, diarrhoea, and visual disturbance. The major concern of tranexamic acid is the potential for deep venous thrombosis. In a case-control study using data from the British General Practice Research Database, women taking tranexamic acid had a 3-fold higher risk of developing deep vein thrombosis (DVT). Tranexamic acid should not be taken together with combined oral contraceptive pills, which by themselves increase the risk of DVT. Tranexamic acid should be avoided in women with known pre-existing conditions that make them prone to developing a thrombosis.

Menstrual cycle suppression

When external sex hormones are administered, the production of ovarian-stimulating hormones, FSH and LH from the pituitary gland at the base of the brain, is suppressed. Therefore, cyclic changes in the ovaries are also suppressed, and there are no mid-cycle oestrogen surges.

Sex hormone pills in the form of combined oestrogen and progestogen pills (so-called combined oral contraceptives pills or COCPs), or progestogen-only pills (Minipills), can be used for this purpose.

Many COCPs contain a mixture of active pills with drugs in them, and a number of sugar pills that have no active drugs in them, to mark the days when a woman is expected to have a period. The active pills can be used continuously for several months. By skipping periods, a woman can avoid period-related issues. However, the withdrawal bleed could be heavy and difficult to manage. There are currently no well-conducted trials to support this strategy for adenomyosis, and therefore it should probably not be considered as a long-term solution. As there are more than thirty COCP brands available in Australia, choosing the right one might not be an easy task, and it’s best to discuss this with your GP.

Progestogen only pills can be taken constiuously to manage adenomyosis symptoms. Both Slinda and Visanne can be used. Vissane is more effective for symptom control but is not tested for contraception; Slinda is more effective for contraception but less effective for symptom control.

Find out more about Visanne

Medically induced temporary menopause

We know that adenomyosis is an oestrogen-dependent condition. Hormonal manipulation to turn off oestrogen production might cause regression of adenomyosis. This can be achieved by using Gonadotropin-Releasing Hormone Agonists (GnRHa) acting act at the pituitary level. They turn off the stimulating hormone directed towards the ovary, which will then stop making sex hormones and prevent a woman from having a period. It’s like a medically induced temporary menopause. These drugs can therefore shrink the adenomyotic tissue and the overall size of the uterus. GnRHa can be administered as a twice daily nasal spray or monthly/3-monthly depot injection.

Woman might have side effects like those experienced when going through menopause: hot flushes, mood changes, and reduced bone density. These side effects limit the duration of treatment to 3-6 months.

Once the treatment is stopped, a woman’s adenomyosis might bounce back. Symptoms can recur, and the uterus may increase to pre-treatment size.

Pregnancy is possible soon after cessation of the treatment. Therefore, GnRHa can be used as a temporary solution for women who are severely symptomatic but want to conceive. GnRHa can also be used as pre-treatment with the hope to increase the success of IVF.

Ryeqo can be used to treat endometriosis and one can argue it might also be useful for adenomysis, but this is not yet proven by research studies.

Find out about Ryeqo for Fibroids and Endometriosis

Should you wait for menopause?

Is telling women to wait for menopause good advice? Probably not.

Since adenomyosis is an oestrogen-dependent condition, symptoms should subside after menopause. On average, an Australian woman would expect to enter menopause at around the age of 52, so depending on how far she is from menopause, and for all the years leading up to it, adenomyosis is not going to get better by itself. In fact, symptoms can get worse the nearer she gets to menopause, as adenomyosis becomes more extensive after each month’s cyclical oestrogen stimulation. Furthermore, the closer she is to menopause, a woman’s cycle can become irregular and unpredictable. This can be difficult to manage for those suffering from heavy menstrual bleeding. Accidental leak-through and embarrassment are real concerns. Not knowing when her heavy flooding period is going to come is particularly stressful. At this stage, medical therapies might no longer be effective.

In the past, hysterectomy was the only solution. Nowadays, we have progesterone-releasing IUDs (Mirena and Kyleena), and UAE, which can be used alone or in conjunction with each other, especially when medical therapies are not effective or are undesirable.

See all Adenomyosis Treatment Options

References

1. Pharmacovigilance Centre Prescriber Update on Tranexamic acid 24(2): 26-27 October 2003 http://www.medsafe.govt.nz/profs/puarticles/txaclot.htm Accessed 9 August 2015
2. Nonsteroidal anti-inflammatory drugs for dysmenorrhoea. Marjoribanks J, Proctor M, Farquhar C, et al. Cochrane Database Syst Rev 2010(1):CD001751
3. Role of medical therapy in the management of uterine adenomyosis. Vannuccini, Silvia; Luisi, Stefano; Tosti, Claudia; Sorbi, Flavia; Petraglia, Felice Fertility and Sterility, March 2018, Vol.109(3), pp.398-405
4. Treatment of endometriosis with estrogen-progestin combination and progestogens alone. Moghissi KS Clin Obstet Gynecol 1988; 31:8238.
5. Choosing a combined oral contraceptive pill. M Stewart, K Black. Australian Prescriber 2015; 38:6-111 Feb 2015
6. Effects of short course buserelin therapy on adenomyosis: a report of two cases. Huang FJ, Kung FT, Chang SY, Hsu TY. J Reprod Med Obstet Gynecol. 1999; 44:741744.
7. Treatment of adenomyosis with long-term GnRH analogues: a case report. Grow DR, Filer RB. Obstet Gynecol. 1991;78(3 Pt 2):538539.
8. Adenomyosis: review of the literature. Garcia L, Isaacson K. J Minim Invasive Gynecol. 2011; 18:428437.

The post Medical Therapy for Adenomyosis appeared first on Sydney Fibroid Clinic.

• Mirena is a progestogen-releasing contraceptive IUD.
• Mirena alleviates adenomyosis-related HMB and pain in a majority of women.
• Common side effects are irregular bleeding and spotting.
• Mirena might not work well for a uterus larger than 150ml.

Failing Mirena , check out UAE as an non-surgical alternative to hysteretomy

Mirena for Adenomyosis

Mirena, a hormone-releasing IUD, is commonly used for heavy menstrual bleeding and period pain. A significant majority of women have a positive experience with it in terms of its effectiveness and lack of side effects. Apart from UAE, Mirena is currently the best-evaluated and the most efficacious non-surgical treatment for adenomyosis-related heavy bleeding and period pain.

Mirena is also an effective contraceptive device that might be appropriate for some women, as once removed, they can try to get pregnant straight away. It’s also useful in treating period pain associated with endometriosis, which often coexists with adenomyosis.

Many women might stop having a period altogether. This happens in up to 8% of women at 6 months, and 16.8% at 12 months. This is desirable for some women but might not be for others.

As with all medical therapies, Mirena isn’t effective for everyone, and some women do develop significant side effects. In our specialist tertiary referral clinic, we tend to see women who’ve found that Mirena didn’t help them or were trying to avoid having it.

Its failure could be simply ineffectiveness. For these women, their menstrual bleeding was still heavy and/or painful. In some, their bleeding had been so heavy, that the Mirena was expelled. For others, it might have worked for some time, but as the disease progressed, it stopped working.

One of the common issues with Mirena is that it might take 3 to 6 months to “settle in” and become effective. During that time, there could be irregular bleeding, continuous light bleeding, or spotting. Women are often encouraged to persevere for that length of time, with the expectation that it might eventually work. Many women follow this advice but then become rather fed up with having to wear a pad every day for so many months. They get frustrated and just want it out. What follows is that, unless there are other backup therapies in place, they might suffer from a severe withdrawal bleed with flooding and clotting, once their Mirena is removed.

Some women are unlikely to have a good response with Mirena. Sadly, we didn’t know about this until recently. A 2016 study from Korea has shown Mirena is less effective in women with more extensive adenomyosis. They found that if a woman’s uterus was larger than 150ml, Mirena was more likely to be discontinued. And in women whose uterus was larger than 314ml in volume, the rate of discontiuation was 70%.

When the uterine cavity is distorted due to fibroids or focal adenomyosis, Mirena might not sit well, be difficult and risky to insert, and is more likely to be expelled.

Some women come to see us looking for alternatives. Others have experienced side effects like weight gain, mood swings, bloating, and abdominal pain. Many are concerned about having it inserted after reading about these side effects online or hearing about them from their friends.

Mirena insertion can be uncomfortable for women who haven’t had a vaginal birth, because the cervical canal can be rather tight, so it might have to be done under sedation with local anaesthetic gel.

If your Mirena is not effective or if you are developiong side effects, UAE (uterine artery embolisation) is effective in alleviating heavy menstrual bleeding and period pain. UAE is a non-hormonal and non-surgical treatment, and can be used as an alternative to hysterectomy.

Learn more about UAE

More about Mirena and adenomyosis

Mirena is an intrauterine device that slowly releases a tiny dose of progestogen over 5 years. It was initially designed as a contraceptive device, but it has been commonly used for control of heavy menstrual bleeding.

It’s T-shaped, with two soft plastic flexible arms measuring 3.2 cm total width across. The tubular body, 3.2 cm in height, houses the progestogen reservoir. The device can be inserted in a doctor’s office, or if insertion difficulty is expected, it can be done under ultrasound guidance with sedation.

We don’t completely understand how it reduces heavy menstrual bleeding, but it has been hypothesised to work in two ways. First, the slowly released progestogen causes thinning of the endometrial lining and therefore decreases the amount of menstrual flow. Second, the high local concentration of progestogen turns down the responsiveness of oestrogen receptors in the adenomyotic tissues and prevents oestrogen stimulation of the adenomyotic foci, causing them to shrink. This allows better uterine muscle contraction to help reduce menstrual blood loss.

A study from the Women’s Health Teaching and Research Hospital in Turkey confirmed the effectiveness of Mirena in reducing menstrual blood flow. The study compared Mirena with abdominal hysterectomy. It was published in 2011 in the journal “Fertility and Sterility” and showed a similar outcome in controlling heavy menstrual bleeding. This was a randomised control study, with 43 women assigned to Mirena and 43 assigned to hysterectomy. The haemoglobin level of the women in the study was measured at 6 and 12 months. Both groups showed comparable increase in haemoglobin by 20 grams/L. At 6 months, with 23.8% of women reporting having no period bleeding, while at 12 months, 51.4% reported no more period bleeding.

The side effects reported were headache (11.9%), breast tenderness (7.1%), acne (4.8%), and transient depression (2.4%). Health-related quality of life was measured and showed improvement in both groups. Mirena was superior to hysterectomy on improvement in psychological and social life. The study concluded that Mirena may be a promising alternative to hysterectomy.

A 3-year follow-up study from Beijing O&G Hospital in China, showed Mirena was also effective in reducing period pain. The study followed 94 women with adenomyosis treated with Mirena. A significant drop in menstrual pain score was noted, from 77.9 at baseline, to 16 at 12 months and 11.8 at 36 months. However, the patient satisfaction rate was only 56.3% at 12 months. The common side effects reported were prolonged light bleeding (25%) or irregular bleeding (14%). Other less-common side effects were weight gain (28.7%), ovarian cyst formation (22.3%), lower abdominal pain (12.8%), acne (6.4%), and transient depression (1.1%). These side effects might have contributed to the less-than-ideal satisfaction rate. At one year, 12% of Mirena had been expelled, and10.6% were removed due to side effects, resulting in a 22.6% discontinuation rate.

Possible Mirena Side Effects

(List from Bayer Consumer Medicine Information)

• Nervousness, depressed mood, mood swings
• Lower abdominal/pelvic pain or back pain, period pain
• Bleeding changes, including:
• increased or decreased menstrual bleeding,
• spotting, infrequent or light periods,
• absence of bleeding
• Headache, migraine, nausea
• Acne, excessive hairiness
• Tender or painful breasts
• Itching, redness, and/or swelling of the vagina, vaginal discharge
• Weight gain
• Decreased libido
• Expulsion of Mirena

If you are not tolerating these side-effects, consider UAE as a non-hormonal treatment, effective in 90% of women with heavy and painful periods. Learn more about UAE.

References

1. Mirena Consumer Medicine Information
   https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-CMI-03485-3&d=202010031016933
2. FDA Data
   https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021225s019lbl.pdf
3. Levonorgestrel intrauterine system associated amenorrhea: a systematic review and metanalysis, Jill E. Sergison, Lauren Y. Maldonado, Xiaoming Gao, David Hubacher, AJOG Systemic Reviews| Vol 220, Issue 5, P440-448.E8, MAY 01, 2019
4. An update on the pharmacological management of adenomyosis. Streuli I, Dubuisson J, Santulli P et al. Expert Opinion on Pharmacotherapy, 11/2014, Volume15, Issue 16
5. Adenomyosis: A Clinical Review of a Challenging Gynecologic Condition. Struble, Jennifer; Reid, Shannon; Bedaiwy, Mohamed A. Journal of Minimally Invasive Gynecology. 2016 23 (2): 164185.
6. Comparison of levonorgestrel intrauterine system versus hysterectomy on efficacy and quality of life in patients with adenomyosis. Ozdegirmenci O, Kayikcioglu F, Akgul MA, et al. Fertil Steril 2011;95(2):497-502
7. The LNG-IUS study on adenomyosis: a 3-year follow-up study on the efficacy and side effects of the use of levonorgestrel intrauterine system for the treatment of dysmenorrhea associated with adenomyosis. Sheng, J, Zhang, J P, Zhang, W Y et al. Contraception, 2009, Volume 79, Issue 3
8. Relationship between uterine volume and discontinuation of treatment with levonorgestrel-releasing intrauterine devices in patients with adenomyosis. Lee, Ki Hwan; Kim, Jang Kew; Lee, Min A; Ko, Young Bok; Yang, Jung Bo; Kang, Byung Hun; Yoo, Heon Jong Archives of Gynecology and Obstetrics, 2016, Vol.294(3), p.561(6)

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Uterine artery embolisation (UAE)  is a safe, minimally invasive, non-surgical alternative to a hysterectomy. Reducing heavy periods and relieving pain, the procedure has been shown to be as effective in 90% of women suffering from adenomyosis. Having had UAE, 95% of women are able to avoid a hysterectomy.

What Is Uterine Artery Embolization (UAE) for Adenomyosis?

UAE is suitable for women who have failed conservative medical therapy or Mirena IUD, yet trying to avoid a hysterectomy.

The procedure and its benefits can be summarised as follows:

• Local anaesthetic procedure
• Proven to be safe and effective
• 90% patient satisfaction rate
• No surgical cuts, no general anaesthesia
• 1 – 2 nights hospital stay
• 1-week recovery
• Keep your uterus and pelvic floor intact

Uterine artery embolisation (UAE) means means blocking of the arteries supplying the uterus. It is performed by an interventional radiologist. Only a tiny nick on the skin is needed to allow insertion of a small 1 – 2mm diameter tube called catheter into the femoral artery in the groin. The catheter is navigated to the uterine artery under X-ray guidance. Tiny  particles are then  injected inside the uterine arteries to block the blood flow, thereby starving and killing the adenomyosis tissue. Normal uterine tissue has immense capacity to recruit dormant vessels are therefore remains unharmed.  
The procedure is suitable for women who wish to avoid a hysterectomy, keep their uterus and recover quickly.

Learn more About UAE

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However, glands in the muscle (adeno= glands; myosis in the muscle) will be trapped. Some has described this as sealing off the juice on the BBQ hot plate. Bloating and period pain can get worse.

Endometrial Ablation as Adenomyosis Treatment

Even with modern technology, adenomyosis deeper than 2.5mm cannot be treated by ablation, according to a 2015 study.

If MRI is used for diagnosis, the depth is 12mm minimal. Therefore, adenomyosis diagnosed on MRI should not be treated with ablation.

In the past, when ablation failed to treat adenomyosis or if pain is worse after ablation, hysterectomy is to follow.

Today, there is an alternative to hysterectomy.

If you had ablation and the pain has gone worse, UAE might help to kill off adenomyosis tissue and alleviate pain.

Learn More About Endometrial Ablation

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Hysterectomy is a major operation that require general anaesthetic, few days in hospital and up to 4 to 6 weeks of recovery.

Hysterectomy for Adenomyosis Risks and Side Effects

Surgical risks include anaesthetic complications, blood transfusion, infection, wound issues, and rarely injuries to bowel, bladder and ureter (tube connecting kidney to bladder). The overall risk of severe complication from hysterectomy is 3.5 to 11% and hysterectomy mortality rate can be as high as 0.15%.

Long term side effects of hysterectomy are prolapse and urinary incontinence, early menopause and higher risk of cardiovascular disease (even with ovaries left behind), change of sexual feeling and constipation, and so called post hysterectomy syndrome with depression and lethargy.

If you have uterine cancer, your only choice may be to remove the uterus. However, an overwhelming amount of hysterectomies in developed countries – like Australia and the United States – are performed for benign conditions such as fibroids and adenomyosis.

Adenomyosis Alternative Treatment to Hysterectomy

In the past, when conservative treatments fail or are deemed unsuitable, women are faced with the difficult decision to put up with symptoms or having a hysterectomy.

Today, there are now many effective, non-surgical forms of adenomyosis treatment, hysterectomies for adenomyosis should be considered as a last resort, if all other less invasive methods have failed. Depending on your specific situation, medical therapy, Mirena IUD (56% patient satisfaction) or uterine artery embolisation (90% patient satisfaction) should be considered before embarking on hysterectomy.

Find out about UAE as Alternative to Hysterectomy
Hysterectomy in-depth discussion

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Can you remove adenomyosis with surgery?

Unlike fibroids, which can be easily separated from the normal uterine wall, adenomyotic tissue does not have a clear boundary with the normal myometrium.

Surgeons often find it difficult to determine where adenomyosis stop and where normal myometrium starts. The removal is either incomplete, leaving behind adenomyotic tissue which can continue to grow and cause problems, or a larger than necessary amount of normal myometrium around the adenomyosis might have to be removed.

Surgeons might have been misled by incorrect ultrasound diagnosis and inadvertently went ahead with surgery, with the intention to remove a “fibroid”. Half way through the surgery, it is then realized that the “fibroid” cannot be separated out from uterus and in fact it was adenomyosis that they are dealing with, and that surgery might need to be abandoned.

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