Aromatase inhibitors or gonadotropin-

releasing hormone agonists for the

management of uterine adenomyosis:

A randomized controlled study

Aboubakr Elnashar Benha university Hospital

Ahmed Badawy Mansura university Hospital

Alaa Mosbah Mansura university Hospital

Egypt

Aboubakr Elnashar

Adenomyosis of the uterus:

Common amongst women in their reproductive

years (Farquhar et al, 2006).

1% of women

With improved imaging: diagnosis is more frequent.

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Although adenomyosis & endometriosis are

different diseases, both of them grow& regress in an

oestrogen-dependent fashion (Kitawaki et al,2006).

Adenomyotic tissue contains:

1. Steroid receptors

2. Aromatase& sulphatase enzymes.

Circulating &locally produced oestrogens stimulate

the growth of tissue mediated by the oestrogen

receptors.

Aboubakr Elnashar

To date, there is no agreement on the most

appropriate therapeutic methods for managing

women with uterine adenomyosis who want to

preserve their fertility (Wang et al, 2009).

Hormonal treatment that aims to reduce the

proliferation of endometrial cells is promising, but

there is a paucity of well-designed studies to guide

treatment.

There is a strong need to develop pharmacological

agents that provide an efficient outcome (Farquhar et al,

2006).

Aboubakr Elnashar

GnRHa: in adenomyosis (Wood et al, 2001).

Constant hypoestrogenic state Amenorrhoea

Control of pain

Uterine shrinkage.

But, pure antiestrogen may offer some advantage in

the treatment of adenomyosis& trials are required to

assess its usefulness.

Aboubakr Elnashar

AI: in Leiomyoma (Parsanezhad et al,2010).

Reduction of leiomyoma& uterine volumes GnRHa &AI concomitantly: in adenomyiosis (Kimura

et al, 2007).

Assuming aromatase production activity in the

adenomyosis lesion This stimulated us to undergo this study

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Objective: To examine& compare the efficacy of AI vs. GnRHa

in premenopausal women with uterine adenomyosis.

Design: Prospective RCT

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Setting: •Teaching hospitals affiliated with Mansoura

University

•Delta Fertility Center, Egypt.

Patients: •32 patients with a uterine adenomyosis

•Randomized into two treatments groups (A& B)

using a random table.

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Interventions: •Group A: oral letrozole (2.5 mg/d)

•Group B: IM triptorelin (3.75 mg/mo) for 12 w.

Main outcome measures: •Uterine& adenomyoma vol at baseline& during

treatment at weeks 4, 8,& 12.

•Symptoms at the start& after 12 weeks of the

treatment.

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Letrozole

group

(n=15)

GnRHa

group

(n=16)

X2 P

Age

BMI

Presenting symptoms

- No symptoms

- Chronic pelvic Pain

- Dysmenorrhoea

- Menorrhagia

- Metrorrhagia

- Dyspareunia

- Subfertility

Associated pathology

Solitary adenomyosis

Diffuse adenomyosis

Combined

37 (±3.44)

27 (±2.3)

3 (20%)

12 (80%)

7 (46.7%)

5 (33.3%)

4 (26.7%)

6 (40%)

8 (53.3%)

5 (33.3%)

6 (40%)

9 (60%)

5 (33.3%)

35 (±2.8)

25 (±3.1)

2 (12.5%)

14 (67.5%)

8 (53.3%)

7 (46.7%)

4 (26.7%)

8 (50%)

7 (46.7%)

7 (46.7%)

8 (50%)

8 (50%)

7 (46.7%)

0.08

0.10

0.23

0.03

0.01

0.16

0.01

0.12

0.10

0.16

0.12

0.09

0.16

0.74

0.75

0.62

0.86

0.91

0.69

0.93

0.73

0.79

0.69

0.73

0.76

0.69

Patients' characteristics

P value <0.05 was significant

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Letrozole

group

(n=15)

GnRHa

group

(n=16)

X2 P

•Leiomyoma

•Pelvic endometriosis

•Endometrial polyps

•Endometrial hyperplasia

•Hydrosalpinx

5 (33.3%)

2 (13.3%)

1 (6.7%)

3 (20%)

1(6.7%)

5 (31.2%)

3 (13.8%)

-

2 (12.5%)

1 (6.3%)

0.01

0.12

-

0.23

0.10

0.92

0.72

-

0.62

0.96

Associated pathology

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Letrozole group

(n=15)

GnRHa group

(n=16)

t P CI

•Baseline 125.45-431.89

(255.94 ±43.3)

135.89-393.16

(264.52 ±41.2)

0.56 0.576 39.6-22.45

• At 4 W

Decline %

101.11-390.12

(245.61 ±15.3)

4.04%

112.03-311.23

(211.63 ±14.9)

19.99%

6.263 0.001 22.88-45.07

• At 8 W

Decline %

91.23-300.05

(195.62 ±35.6)

23.57%

85.14-250.06

(167.6 ±36.5)

36.64%

2.16 0.039 1.50-54.53

• At 12 W

Decline %

63.87-210.18

(137.02 ±29.8)

46.46%

67.36-165.53

(116.44 ±28.9)

55.98%

1.951 0.06 0.98-42.14

Changes in uterine volume and volume decline

percentage

•There is a statistically significant differences in the post treatment uterine

volumes of the two groups at 4 and 8 w, but not at 12 w.

•Letrozole group showed a slower rate of uterine volume reduction.

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Letrozole group

(n=15)

GnRHa group

(n=16)

t P CI

•Baseline 16.15-27.74

(21.94 ±2.5)

16.85-29.20

(23.02± 2.4)

1.227 0.229 2.82-0.72

• At 4 W

Decline%

14.81-25.31

(20.06 ±2.9)

8.57%

14.22-26.01

(21.71 ±2.7)

5.69%

1.640 0.11 3.706-0.407

• At 8 W

Decline%

10.05-20.81

(15.43± 2.3)

29.67%

11.21-18.91

(15.06 ±2.1)

34.58%

0.468 0.64 1.246-1.986

• At 12 W

Decline%

8.95-17.00

(12.97 ±1.9)

40.88%

9.24-14.19

(11.71± 1.8)

49.13%

1.896 0.067 0.099-2.619

Changes in adenomyoma volume& volume decline

percentage

•No significant differences between the post treatment adenomyoma volumes

of the two groups at 4, 8 and 12 w.

•Significant reduction in adenomyoma vol. in both groups at 12 w of treatment. Aboubakr Elnashar

Improved Letrozole

group

(n=15)

GnRHa

group

(n=16)

X2 P

Chronic pelvic pain

Dysmenorrhoea

Menorrhagia

Metrorrhagia

Dyspareunia

Subfertility

10/12 (83.3%)

4/7(57.1%)

3/5(60%)

1/4(25%)

2/6(33.3%)

2/8(25%)

13/14(92.8%)

8/8(100%)

7/7(100%)

3/4(75%)

6/8(75%)

0/7 (0%)

0.85

0.49

0.57

0.41

0.40

0.21

0.04

0.48

0.32

0.69

0.70

1.59

Symptom improvement

•No woman in Letrozole group suffered from hot flashes, while 81.25% women

of GnRHa group reported various degrees of hot flashes.

•Two out of eight subfertile women got pregnant during treatment in Letrozole

group.

•Although GnRHa was more effective than letrozole in relieving symptoms, this

difference was not statistically significant.

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0

50

100

150

200

250

300

Baseline 4 W 8 W 12 W

Letrozole group

GnRHa group

Changes in uterine volume

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0

5

10

15

20

25

Baseline Wk 4 Wk 8 Wk 12

Letrozole group

GnRHa group

Changes in adenomyoma volume

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Conclusion Management of uterine adenomyoisis using AI is

useful in women for whom temporary reduction in

volume is aimed& no surgical intervention is planned

for any reason.

Aboubakr Elnashar