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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.
Aboubakr Elnashar
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
Aboubakr Elnashar
Objective: To examine& compare the efficacy of AI vs. GnRHa
in premenopausal women with uterine adenomyosis.
Design: Prospective RCT
Aboubakr Elnashar
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
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
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
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
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
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.
Aboubakr Elnashar
0
50
100
150
200
250
300
Baseline 4 W 8 W 12 W
Letrozole group
GnRHa group
Changes in uterine volume
Aboubakr Elnashar
0
5
10
15
20
25
Baseline Wk 4 Wk 8 Wk 12
Letrozole group
GnRHa group
Changes in adenomyoma volume
Aboubakr Elnashar
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