This randomized controlled trial compared the effects of metformin and combined oral contraceptives (COCs) in adolescent women with polycystic ovary syndrome (PCOS) over 24 months. 119 adolescent girls were randomly assigned to receive metformin, COCs, or no treatment (control group). Both metformin and COCs significantly improved cycle regularity and hirsutism compared to the control group. However, metformin was associated with significant improvement in insulin sensitivity, while COCs deteriorated insulin sensitivity. The study concludes that metformin and COCs have comparable effects on symptoms, but metformin may have metabolic advantages in adolescent PCOS patients.

1. RCT of the effects of
Metformin Vs
COCs
in adolescent
PCOS
women through a 24 month
follow up period
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2. ADOLESCENT PCOS
Affects a substantial number of girls with
increasing incidence
{increasing prevalence of childhood obesity}
(Hassan et al, 2007).
±Progressive course with the potential to develop
full-blown picture of adult PCOS
(evidence is contradictory)
(Coviello et al, 2006)
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3. Therapeutic goals:
symptomatic and prophylactic:
Restoration of body weight
Cycle regulation
Reducing signs of hyperandrogenism
Prevention of long term health hazards.
Infertility
Metabolic syndrome
Obesity
Diabetes
Heart disease.
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4. Diagnosis:
2 years after menarche
{overlap between normal pubertal development and
characteristic features of PCOS}
Hyperandrogenemia (Serum testosterone >1
µg/ml): the most reliable finding
NIH:
Rotterdam criteria: All 3 OR
(Carmina et al, 2010)
AE-PCOS Society criteria
(Legro et al, 2013).
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5. ABOUBAKR ELNASHAR

6. Management
Lifestyle modification
Weight reduction and excerise
{obesity worsens the endocrine profile of these
women and increases the risk of infertility}
decrease androgen effects
increase ovulation
improve insulin sensitivity.
Metformin
COC
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7. There are few studies comparing COC and Met in
adolescents PCOS
To our knowledge, this study is 1st to follow up
adolescent PCOS women for a period of 2 years.
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8. OBJECTIVE
To compare Met and COC effects over 24 mo in
adolescent PCOS.
Design: RCT
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9. Sample size
of the study groups was calculated
32 patients were required for each study group.
119 adolescent girls
Age: 15–20 years
Hirsutism, acne and menstrual disturbances.
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10. PCOS:
Oligomenorrhoea (<6 cycles/year) and
Serum testosterone >1 µg/ml
Randomization
computer-generated random-number tables:
Group A (n= 40): Met: 1700 mg/d
Group B (n= 40): COC (30 µg EE and150µg desogestrel, Marvelon)
Group C (n= 39): Control.
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11. Initial assessment
B wt, Waist-to-hip ratio, Ferriman–Gallway score,
Total testosterone, FSH, LH, prolactin,
transaminases.
Insulin resistance
75 g OGTT
GIR
Fasting and after load insulin
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12. Outcome measures:
Primray
Improvement in cycle rhythm and hirsutism.
Secondary
Weight loss
Serum testosterone levels
Fasting and after load serum insulin levels
GIR
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13. Control group
(n=39)
Metformin group
(n=40)
OCP group
(n=40)
Control group
(n=35)
Metformin group
(n=37)
OCP group
(n=39)
Control group
(n=32)
Metformin group
(n=36)
OCP group
(n=36)
Control group
(n=29)
Metformin group
(n=33)
OCP group
(n=34)
Analysed
(n=25)
Analysed
(n=32)
Analysed
(n=33)
randomized (n=119)
3 DOs (side effects)
1 DO (side effects)
3 DOs (2 non-compliant, 1
not satisfied with drug)
1 DO (lost for follow up)
1 DO (non-compliant)
3 DOs (weight gain)
2 DOs (1 side effects, 1
weight gain)
1 DO (side effects)
4 DOs (worsening
symptoms asked
for treatment)
3 DOs (2 worsening
symptoms, 1asked for
treatment)
3 DOs (lost for follow
up)
4 DOs (lost for follow
up)
6m
12 m
18 m
24 m
Consort flow chart
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14. A B C
mean SD mean SD mean SD
Age (Years) 17.20 2.00 16.90 1.60 17.00 2.10
Weight (Kgs) 87.00 6.00 91.00 3.00 84.00 6.00
Testosterone (µg/ml) 1.50 0.40 1.30 0.50 1.20 0.40
Fasting Insulin (µIU/L) 18.60 3.00 15.00 3.00 15.00 2.00
After-load Insulin (µIU/L) 126.00 34.0 103.00 19.00 100.00 21.00
GIR 4.10 0.30 4.40 0.20 3.90 0.50
Clinical characteristics of the three study groups
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15. Cycle regularity
Sig improvement in Group A and Group B:
(92.5% and 100%)
compared to the control group
Hirsutism
Subjective improvement in Group A and Group B
(25% and 40%)
compared to the control group
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16. Group
Baseline 6 months 12 months 18 months 24 months
mean SD mean SD mean SD mean SD mean SD
T(µg/ml)
A 1.50 0.40 0.80 0.10 1.10 0.40 1.30 0.30 1.20 0.30
B 1.30* 0.50 1.00 0.30 0.90 0.40 0.60 0.30 0.70* 0.20
C 1.20 0.40 1.30 0.20 1.00 0.20 1.60 0.20 1.50 0.40
Fasting
insulin
(µIU/L)
A 18.60* 3.00 15.00 4.00 14.00 2.00 9.00 2.00 10.00* 3.00
B 15.00 3.00 14.00 2.00 16.00 4.00 21.00 3.00 19.00 4.00
C 15.00 2.00 13.00 3.00 21.00 5.00 20.00 4.00 22.00 3.00
After-load
insulin
(µIU/L)
A 126.00 34.00 100.00 31.00 91.00 21.00 82.00 16.00 64.00* 15.00
B 103.00 19.00 100.00 21.00 135.00 41.00 167.00 34.00 187.00 22.00
C 100.00 21.00 110.00 21.00 133.00 29.00 103.00 37.00 111.00 12.00
GIR
A 4.10* 0.30 4.00 0.30 3.90 0.30 4.80 0.40 4.60* 0.50
B 4.40* 0.20 4.20 0.30 3.60 0.40 3.60 0.30 3.10* 0.30
C 3.90 0.50 3.90 0.30 4.00 0.30 3.50 0.20 3.10 0.30
Weight
(Kg)
A 87.00* 6.00 82.00 8.00 83.00 5.00 79.00 6.00 72.00* 5.00
B 84.00 9.00 87.00 8.00 90.00 9.00 91.00 10.00 91.00 3.00
C 84.00 6.00 91.00 5.00 97.00 8.00 93.00 7.00 99.00 9.00
Follow up parameters for the 3 study groups.
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17. Group A: sig drop from 1.5 to 0.8 µg/ml by 6 mo, by 24 mo
:1.2 µg/ml, which is not significantly different from initial values.
Group B: sig decline from1.3 to 0.7 µg/ml by the end of 24 mo
Group C: non-sig increase from 1.2 to 1.5 µg/ml.
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18. Group A: sig increase from 4.1 to 4.6 {improvement in insulin sensitivity}
Group B: sig decrease from 4.4 to 3.1 {deteriorating insulin sensitivity}.
Group C: non sig decrease from 3.9 to 3.1ABOUBAKR ELNASHAR

19. Group A: sign decline from 87 to 72 kg
Group B: non-significant gain from 84 to 91 kg
Group C: non-significant gain from 84 to 99 kg
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20. Group A: sign decline from 126 to 64 µIU/L
Group B: sig increase from 103 to 187 µIU/L
Group C: non sig increase from 100 to 111 µIU/L
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21. Cochrane SR, 2007
After 12 mo;
No difference in the therapeutic effectiveness
between Met and COC on hirsutism and acne,
but Met resulted in a reduction in fasting insulin
and lower triglyceride levels than COC.
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22. CONCLUSIONS
Met and COC have comparable therapeutic
effectiveness on cycle regularity and hirsutism.
Met was associated with a sig improvement in
insulin sensitivity
COC was associated with a deterioration of
insulin sensitivity
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23. RECOMMENDATION
The choice of the proper line of therapy should be
tailored for every patient, according to
Age
Stage in life
Symptoms
Personal and familial risk indices
Choices.
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24. If the main complaints are limited to acne and
hirsutism:
Met is advantageous having a safer profile than
COC.
If the main aim is menstrual cycle control:
COC have clear advantages in terms of
effectiveness and cost.
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25. THANKS
Hassan El Maghraby
Tamer Nafee
Dalal Guiziry
Ismaeel Fourtia
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