Aromatase in endometriosis

 by Professor Serdar Bulun (USA) and Ros Wood (Australia)

Recently, a few gynaecologists have begun prescribing aromatase inhibitors for women with endometriosis, who have not had success with other treatments or who cannot use other treatments because of their side effects.

Three published phase II (pilot) studies have shown that aromatase inhibitors are effective in the medical treatment of endometriosis. However, a total of only 65 patients were included in these studies.

Although the use of aromatase inhibitors is new in endometriosis, they have been used to treat post-menopausal women with some forms of breast cancer for nearly 10 years. In fact, aromatase inhibitors are currenly the most effective nontoxic drugs for the treatment of postmenopausal breast cancer.

At the moment, the treatment of endometriosis with aromatase inhibitors is still experimental, because the research is still in its early days. Thus far, a phase III study that may lead to approval of their use for the treatment of endometriosis by the United States Food and Drug Administration (FDA), or an equivalent institution, has not been attempted.

How it works

Aromatase is a protein in the body that is responsible for producing oestrogen. Normally, it is found in the ovaries, and to a much lesser extent in the skin and fat.

Research has shown that aromatase is also found in high levels in the ectopic endometrial tissue of women with endometriosis, which contributes to the growth of their endometriosis.

Further research, has shown that inhibiting the aromatase by giving women an aromatase inhibitor suppresses the growth of their endometriosis, and reduces the associated inflammation. This, in turn, significantly reduces their pelvic pain.

Dosage

The aromatase inhibitors used for endometriosis include letrozole and anastrozole. You should not use an aromatase inhibitor if you already have osteoporosis.

In premenopausal women, an aromatase inhibitor is used in combination with another drug that suppresses the ovaries. If used alone, it may stimulate the ovaries and the development of ovarian cysts. The other drug may be an oral contraceptive pill, a progestogen or a GnRH agonist.

If a GnRH agonist is used, calcium, vitamin D and a bisphosphonate (a drug that protects the bones against osteoporosis) should also be taken.

In postmenopausal women, an aromatase inhibitor is used in combination with calcium, vitamin D and a bisphosphonate to prevent osteoporosis of the bones.

Side effects

The most common side effects of aromatase inhibitors are mild hot flushes and decreased libido.

Effectiveness for pain symptoms

To date, only a few studies involving a limited number of women have been conducted. However, those studies indicate that aromatase inhibitors markedly reduce the amount of endometriosis and pelvic pain in most women.

Effectiveness for infertility

Aromatase inhibitors — like all the hormonal treatments for endometriosis — will not improve your chance of conceiving, so they should not be used as a treatment for infertility.

Keeping track

As with all drug treatments, you should visit your gynaecologist about 6–8 weeks after starting the aromatase inhibitor to discuss how the treatment is progressing. Contact your gynaecologist if you develop any problems between scheduled visits.

References

Ailawadi, RK, Jobanputra, S, Kataria, M, Gurates, B and Bulun, SE, Treatment of endometriosis and chronic pelvic pain with letrozole and norethindrone acetate: a pilot study. Fertil Steril 2004; 81: 290-6.

Amsterdam L, GW, Rubin S, Jobanputra S, Wolf M, Bulun SE, Anasrozole and oral contraceptives: A novel treatment for endometriosis. Fertil Steril 2005; 84: 300-4

Bulun, SE, Zeitoun, K, Takayama, K, Noble, L, Michael, D, Simpson, E, Johns, A, Putman, M and Sasano, H, Estrogen production in endometriosis and use of aromatase inhibitors to treat endometriosis. Endocr Relat Cancer 1999; 6: 293-301.

Bulun, SE, Yang, S, Fang, Z, Gurates, B, Tamura, M, Zhou, J and Sebastian, S, Role of aromatase in endometrial disease. J Steroid Biochem Mol Biol 2001; 79: 19-25.

Bulun, SE, Imir G, Utsunomiya H, Thung S, Gurates B, Tamura M, Lin Z. Aromatase in endometriosis and uterine leiomyomata. J Steroid Biochem Mol Biol 2005. In Press.

Noble, LS, Simpson, ER, Johns, A and Bulun, SE, Aromatase expression in endometriosis. Journal of Clinical Endocrinology and Metabolism 1996; 81: 174-179.

Noble, LS, Takayama, K, Putman, JM, Johns, DA, Hinshelwood, MM, Agarwal, VR, Zhao, Y, Carr, BR and Bulun, SE, Prostaglandin E2 stimulates aromatase expression in endometriosis-derived stromal cells. Journal of Clinical Endocrinology and Metabolism 1997; 82: 600-606.

Razzi, S, Fava, A, Sartini, A, De Simone, S, Cobellis, L and Petraglia, F, Treatment of severe recurrent endometriosis with an aromatase inhibitor in a young ovariectomised woman. BJOG 2004; 111: 182-4.

Shippen, ER and West, WJ, Jr., Successful treatment of severe endometriosis in two premenopausal women with an aromatase inhibitor. Fertil Steril 2004; 81: 1395-8.

Soysal, S, Soysal, M, Ozer, S, Gul, N and Gezgin, T, The effects of post-surgical administration of goserelin plus anastrozole compared to goserelin alone in patients with severe endometriosis: a prospective randomized trial. Hum Reprod 2004; 19: 160-167.

Takayama, K, Zeitoun, K, Gunby, RT, Sasano, H, Carr, BR and Bulun, SE, Treatment of severe postmenopausal endometriosis with an aromatase inhibitor. Fertility and Sterility 1998; 69: 709-713.

Tsai, SJ, Wu, MH, Lin, CC, Sun, HS and Chan, HM, Regulation of steroidogenic acute regulatory protein expression and progesterone production in endometriotic stromal cells. Journal of Clinical Endocrinology & Metabolism 2001; 86: 5765-5773.

Zeitoun, KM and Bulun, SE, Aromatase: a key molecule in the pathophysiology of endometriosis and a therapeutic target. Fertil Steril 1999; 72: 961-9.

Zeitoun, K, Takayama, K, Michael, MD and Bulun, SE, Stimulation of aromatase P450 promoter (II) activity in endometriosis and its inhibition in endometrium are regulated by competitive binding of SF-1 and COUP-TF to the same cis-acting element. Molecular Endocrinology 1999; 13: 239-253.

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