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Aromatase
inhibitors as a treatment for 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.
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| 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 (making it
less effective or ineffective) 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.
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| 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 (progesterone-like
drug) such as Provera, or a GnRH agonist
such as Zoladex, Lupron, or Synarel.
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.
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| SIDE
EFFECTS |
The most common side effects of aromatase inhibitors are
mild hot flushes and decreased libido.
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| EFECTIVENESS
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.
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| 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.
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| 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.
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| 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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| SEE
ALSO |
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