Aromatase inhibitors in the treatment of endometriosis

Radosław Słopień, Słopień R, Błażej Męczekalski, Męczekalski B
Przeglad menopauzalny = Menopause review · 2016 · vol. 1(1) , pp. 43–47 · doi:10.5114/pm.2016.58773 · PMID:27095958 · PMC4828508 · W2345914444
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⚙ AI-generated summary by gemini-2.5-flash-lite, 2026-06-07 ⓘ

This review discusses aromatase inhibitors as a potential treatment for endometriosis, particularly in postmenopausal women, by targeting extra-ovarian estrogen synthesis and addressing associated pain and infertility.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 · read from full text ⓘ

This paper is a narrative review of aromatase inhibitors in gynecology, focusing on their use for endometriosis-related pain, infertility, and—separately—potential relevance in postmenopausal endometriosis. It describes aromatase inhibition as a mechanism to reduce extra-ovarian estrogen production that supports a proposed “virtuous cycle” in ectopic endometrial lesions, and summarizes clinical trial and meta-analysis findings that aromatase inhibitors can decrease pain, reduce lesion size, and improve quality of life, particularly when combined with gestagens, oral contraceptives, or GnRH agonists, while noting reported adverse effects and limited evidence regarding bone mineral density changes. The paper explicitly frames surgery as often preferred for postmenopausal endometriosis due to cancer risk and suggests aromatase inhibitors may be more relevant in older patients because postmenopausal estrogen production is largely extra-ovarian. This paper is centrally about endometriosis — it reviews aromatase inhibitors as potential therapies for endometriosis-related pain, postmenopausal endometriosis, and infertility.

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Abstract

Endometriosis is a chronic inflammatory condition in which foci of endometrial tissue grow outside of the uterine cavity. Endometriosis was estimated to affect 176 million women of childbearing potential all over the world in 2010. The presence of extrauterine endometrial tissue is associated with pain and infertility. Typical symptoms of endometriosis include dysmenorrhoea, dyspareunia, heavy menstrual periods (menorrhagia), pelvic pain that is not related to menstrual cycles, dysuria, and chronic fatigue. Medical treatments for endometriosis include combined oral contraceptive pills, danazol, gestrinone, medroxyprogesterone acetate, and gonadotropin-releasing hormone agonists (aGnRHs). A new class of medications called aromatase inhibitors has been identified in recent years as potential therapeutic agents for endometriosis. This article provides general information about aromatase inhibitors, their use in gynaecology, and their adverse effects. In particular, the paper discusses the use of aromatase inhibitors in the treatment of endometriosis in postmenopausal women. Unlike oral contraceptives, gestagens, aGnRHs, and danazol, which suppress ovarian oestrogen synthesis, aromatase inhibitors inhibit mainly extra-ovarian synthesis of oestrogens. Therefore, the use of aromatase inhibitors seems to be particularly relevant in older patients, as most of the body's oestrogen is produced outside the ovaries after menopause. The paper discusses also the use of aromatase inhibitors in the treatment of pain associated with endometriosis and infertility caused by endometriosis.
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Long-term use of aromatase inhibitors is associated with increased risk of osteoporosis and bone fractures [ 18 , 30 ]. The incidence of fractures was 2-11% in women receiving aromatase inhibitors as adjuvant therapy for breast cancer [ 34 , 35 ]. The incidence of bone fractures was 11% ( n = 3092) in the anastrozole group and 7.7% ( n = 3094) in the tamoxifen group after five years of treatment. The incidence of bone fractures was 9.3% among patients receiving letrozole and 6.5% in those treated with tamoxifen after five years of treatment. After six months of treatment with exemestane, BMD decreased by 2.6% ( n = 78) at the lumbar spine. The ASCO (American Society of Clinical Oncologists) guidelines recommend BMD testing once a year to all patients receiving aromatase inhibitors as adjuvant therapy for breast cancer, and treatment with bisphosphonates for those with BMD T-scores ≤ –2.5 [ 36 ]. After six months, combination treatment with anastrozole and goserelin was associated with a greater decrease in BMD than was goserelin alone. This effect was maintained after discontinuation of treatment. However, no patient developed osteoporosis or osteopaenia [ 14 ].

Intro

Endometriosis is a chronic inflammatory condition in which foci of endometrial tissue grow outside of the uterine cavity. The presence of extrauterine endometrial tissue is associated with pain and infertility. Endometriosis was estimated to affect 176 million women of childbearing potential all over the world in 2010 [ 1 ]. It is hypothesised that ectopic endometrial tissue is transplanted by retrograde menstruation (a reversal in the direction of menstrual flow), arises by endometrial metaplasia of the peritoneal serosa, or is carried through the lymphatic system to distant organs in women with a genetic or immunologic predisposition to the disease [ 1 ]. Some authors also suggest possible involvement of neurological factors in the aetiopathology of endometriosis [ 2 ] and point to the relationship between signs and symptoms of endometriosis and the level of oestrogens [ 3 ]. Typical symptoms of endometriosis include dysmenorrhoea, dyspareunia, heavy menstrual periods (menorrhagia), pelvic pain that is not related to menstrual cycles, dysuria, and chronic fatigue [ 4 ]. Endometriosis may cause infertility due to tubal blockage, ovarian cysts, subclinical pelvic inflammatory disease, poor oocyte quality, and impaired endometrial receptivity [ 5 ]. In addition, endometriosis may worsen clinical outcomes in patients treated with assisted reproductive technology (ART) [ 6 ]. Endometriosis is a significant social and economic problem [ 4 , 7 , 8 ]. Medical treatments for endometriosis include combined oral contraceptive pills, danazol, gestrinone, medroxyprogesterone acetate, and gonadotropin-releasing hormone agonists (aGnRHs). A new class of medications called aromatase inhibitors has been identified in recent years as potential therapeutic agents for endometriosis.

Aromatase

Another important issue we should address is treatment of infertility in patients with endometriosis. Many reports suggest lower effectiveness of drug treatment in patients with infertility caused by endometriosis [ 16 , 17 , 21 , 22 ]. Randomised clinical trials provide some evidence that intrauterine insemination (IUI) with ovulation induction may be effective in patients with mild to moderate endometriosis [ 16 , 17 , 23 , 24 ]. Werbrouck et al . [ 25 ] demonstrated that ovulation induction treatment and IUI within six months of surgery may have positive outcomes in patients with mild to moderate endometriosis. Aromatase inhibitors were first used in ovulation induction treatment in 2001 [ 26 ]. Their mechanism of action involves stimulation of pituitary secretion of FSH through the prevention of oestrogen formation from androgens. It was also found that increased interfollicular androgen levels enhance follicular responsiveness to FSH [ 27 , 28 ]. For ovulation induction letrozole is administered at a dose of 2.5-7.5 mg/day on days 3-7 of the menstrual cycle [ 29 ]. When compared to clomiphene, letrozole inhibits oestradiol synthesis rather than its oestrogenic activity. In addition, the half-life of letrozole (∼2 days) is much shorter then that of clomiphene (∼2 weeks). Therefore, the drug has no anti-oestrogenic effect on cervical mucus or endometrium. Letrozole, like clomiphene, is indicated in women with polycystic ovary syndrome (PCOS) and idiopathic infertility [ 29 – 31 ]. Alborzi et al . [ 15 ] compared pregnancy rates and the recurrence rate of endometriosis in 144 women who were treated for two months after laparoscopic surgery for endometriosis. Patients were allocated to one of the following treatment groups: Group 1: 47 subjects treated with letrozole 2.5 mg/day; Group 2: 40 subjects treated with triptorelin 3.75 mg IM injections every 4 weeks; Group 3: 57 subjects who received no active treatments. There was no difference between treatment groups in pregnancy rates (23.4% in Group 1 vs. 27.5% and 28.1% in Group 2 and Group 3, respectively) or recurrence rate of endometriosis (6.4% in Group 1 vs. 5% and 5.3% in Group 2 and Group 3, respectively). Abu Hashim et al . [ 32 ] compared ovulation and pregnancy rates after ovulation induction with letrozole or clomiphene and intrauterine insemination in 136 women with primary infertility, who did not conceive within 6-12 months of laparoscopic surgery for mild to moderate endometriosis. Patients were treated with letrozole 5 mg/day (69 patients, 220 cycles) or clomiphene 100 mg/day (67 patients, 213 cycles) for five days and intrauterine insemination for four cycles. Success rates for pregnancy per cycle and total number of pregnancies were comparable in both treatment groups (15.9% vs. 14.5% and 64.7% vs. 57.2% in the letrozole and clomiphene groups, respectively), even though the number of follicles and serum estradiol levels were significantly higher in the clomiphene group on the day hCG was administered. There were two twin pregnancies in the clomiphene group. Miscarriage and live birth rates were 11.4% vs. 12.9% and 44.9 vs. 40.3 in the letrozole and clomiphene groups, respectively. The authors concluded that letrozole was not superior to clomiphene ovulation induction in combination with a timed intrauterine insemination in patients with mild to moderate endometriosis, who did not conceive within 6-12 months of laparoscopic surgery. The effect of letrozole on IVF outcomes was also investigated. Lossl et al . studied the impact of anastrozole and aGnRH on IVF outcomes in 20 infertile women with ovarian endometrioma, who underwent IVF/intracytoplasmic sperm injection [ 33 ]. Patients received goserelin 3.6 mg SC injection on day 1, day 28, and day 56 in combination with anastrozole 1.0 mg daily on 1-69 days of the treatment period. Then, ovulation induction was started on Day 70. The authors found that treatment with anastrazole and goserelin significantly reduced the size of ovarian lesions and serum CA-125 levels. The mean decrease in endometrioma volume was 29% ( p = 0.007), and the mean decrease in serum CA-125 levels was 61% ( p = 0.001) on days 1-70 of the treatment period. The average number of oocytes retrieved during IVF/intracytoplasmic sperm injection treatment cycles was 7.5 (range: 6.0-10.0). The rate of pregnancy was 45% (9 of 20 subjects). Four patients had a biochemical pregnancy, two had an early miscarriage, and only three (15%) patients gave birth to full-term babies. Although such a high rate of miscarriage (6 of 20 patients) could be accidental, the authors suggest the potential contribution of poor oocyte/endometrium quality due to long-term administration of oestrogen-blocking drugs.

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endometriosisdysmenorrheadyspareuniainfertility

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