Aromatase inhibitors or gonadotropin-releasing hormone agonists for the management of uterine adenomyosis: A randomized controlled study

1. 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

2. 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.
Aboubakr Elnashar

3. 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

4. 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

5. 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

6. 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
Aboubakr Elnashar

7. Objective:
To examine& compare the efficacy of AI vs. GnRHa in premenopausal women with uterine adenomyosis.
Design:
Prospective RCT
Aboubakr Elnashar

8. 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.
Aboubakr Elnashar

9. 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.
Aboubakr Elnashar

10. 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
Aboubakr Elnashar

11. 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
Aboubakr Elnashar

12. 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.
Aboubakr Elnashar

13. 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

14. 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.
Aboubakr Elnashar

15. 0
50
100
150
200
250
300
Baseline
4 W
8 W
12 W
Letrozole group
GnRHa group
Changes in uterine volume
Aboubakr Elnashar

16. 0
5
10
15
20
25
Baseline
Wk 4
Wk 8
Wk 12
Letrozole group
GnRHa group
Changes in adenomyoma volume
Aboubakr Elnashar

17. 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