|
| Reference: | Rautio et al. [75] and Rautio et al. [76] |
| Patient
profile: | Overweight
but not obese PCOS (n = 30) |
| PPAR
agonist: | Rosiglitazone
(4 mg once daily for 2 weeks then 4 mg twice daily for 16 weeks) |
| Metabolic
outcomes: | Serum
C-reactive protein levels, leukocyte count, and alanine aminotransferase
enzyme activity decreased, but lipid and blood pressure did not change. Glucose
tolerance and peripheral insulin response normalized in the rosiglitazone
group. |
| Reproductive
outcomes: | Rosiglitazone
improved menstrual cyclicity, SHBG levels; and decreased serum levels of
androstenedione, 17-hydroxyprogesterone (17-OHP), DHEA and DHEA-S. |
|
| Reference: | Rouzi and Ardawi [77] |
| Patient
profile: | Obese
PCOS (n = 12) |
| PPAR
agonist: | Rosiglitazone
(4 mg twice daily for 3 cycles, CC administered for 5 days starting 3 days
after rosiglitazone initiated) |
| Metabolic
outcomes: | No changes in fasting plasma glucose or HbA(1C) or
IGFBP-3 values. Fasting serum insulin, DHEA-S, androstenedione, and IGF-1
levels decreased significantly and IGFBP-1 exhibited significant increases. |
| Reproductive
outcomes: | Total-T, free-T, LH, and SHBG decreased. Follicular
development and ovulation rate increased, trend for increased pregnancy rate
in group receiving short-term administration of rosiglitazone compared to
matched control receiving metformin. |
|
| Reference: | Mitkov et al. [78] |
| Patient
profile: | Obese,
insulin resistant PCOS (n = 15) |
| PPAR
agonist: | Rosiglitazone
(4 mg/day for 12 weeks) |
| Metabolic
outcomes: | Hyperinsulinemia
and insulin resistance normalized. |
| Reproductive
outcomes: | Total-T
and FAI profile tended to normalise. Number of women with oligomenorrhea was
reduced by 67% |
|
| Reference: | Cataldo et al. [79] |
| Patient
profile: | Insulin
resistant PCOS (n = 11–16/group) |
| PPAR
agonist: | Rosiglitazone
(2, 4 or 8 mg/day for 12 weeks) |
| Metabolic
outcomes: | Steady
state plasma glucose declined and hyperinsulinemia fell in a dose-dependent
manner. |
| Reproductive
outcomes: | Serum
LH, total-T, and free-T were unchanged; SHBG increased. Ovulation occurred in
55%, without significant dose dependence. Before and during treatment,
ovulators on rosiglitazone had lower circulating insulin and free-T and
higher SHBG than nonovulators. |
|
| Reference: | Lemay et al. [80] |
| Patient
profile: | Overweight,
insulin resistant PCOS (n = 15) |
| PPAR
agonist: | Rosiglitazone
(4 mg/day for 6 months) |
| Metabolic
outcomes: | Plasma
insulin, insulin resistance indices and insulin AUC in response to OGTT all
decreased compared to controls receiving antiandrogenic estrogen-progestin.
Effect on lipids was limited. |
| Reproductive
outcomes: | No
significant effect on androgens or hirsutism. |
|
| Reference: | Garmes et al. [81] |
| Patient
profile: | Obese
insulin resistant PCOS (n = 15) |
| PPAR
agonist: | Pioglitazone
(30 mg/day for 8 weeks) |
| Metabolic
outcomes: | Insulin
response to OGTT significantly decreased. |
| Reproductive
outcomes: | Total-T
and free-T levels decreased, SHBG increased, and LH response to GnRH
stimulation decreased. |
|
| Reference: | Yilmaz et al. [82–84] |
| Patient
profile: | Obese
or lean PCOS
(n = 20 obese, n = 20 lean) |
| PPAR
agonist: | Rosiglitazone
(4 mg/day for 12 weeks) |
| Metabolic
outcomes: | Indices
of oxidative stress improved. HOMA, insulin AUC, fasting insulin and
C-peptide levels decreased significantly. Glucose/insulin ratio and BMI
increased |
|
| Reproductive outcomes: | Seurm
levels of free-T, androstenedione, and DHEA-S decreased significantly.
Menstrual disturbances improved in 61.5% of lean and 53.8% of obese
patients. In a second cohort of patients, menstrual cycles became regular in
87.8%. |
|
| Reference: | Tarkun et al. [85] |
| Patient
profile: | Young,
lean PCOS (n = 31) |
| PPAR
agonist: | Rosiglitazone
(4 mg/day for 12 months) |
| Metabolic
outcomes: | Fasting
insulin and insulin resistance indices significantly improved. No changes in
BMI, waist circumference, serum total cholesterol, or LDL-C. Serum C-reactive
protein levels decreased; and endothelium-dependent vascular responses
improved. |
| Reproductive
outcomes: | Significant
decreases in serum T, although no change in FSH and LH levels. Hirsutism
score decreased significantly after treatment. 77.4% of women reverted to
regular menstrual cycles. Levels of SHBG increased significantly after
treatment. |
|
| Reference: | Dereli et al. [86] |
| Patient
profile: | Nonobese
PCOS (n = 20/group) |
| PPAR
agonist: | Rosiglitazone
(2 mg/day or 4 mg/day for 8 months) |
| Metabolic
outcomes: | 75%
of women in the 2 mg group and 95% in the 4 mg group achieved normal glucose
tolerance. Improved insulin resistance in a dose-related fashion, without adverse events
or liver enzyme elevations. |
| Reproductive
outcomes: | Decreased
free-T levels were better in the 4 mg group than the 2 mg group, and 70% of
women in the 2 mg group and 85% of women in the 4 mg group achieved ovulatory
menses. |
|
| Reference: | Mehta et al. [87] |
| Patient
profile: | Obese
PCOS (n = 9) |
| PPAR
agonist: | Pioglitazone
(45 mg/day for 20 weeks) |
| Metabolic
outcomes: | Significant
improvement in insulin sensitivity |
| Reproductive
outcomes: | LH
levels, LH pulse frequency and amplitude, as well as gonadotropin responses
to GnRH were not influenced. |
|
| Reference: | Ortega-González et al. [88] |
| Patient
profile: | Obese,
insulin resistant PCOS (n = 25) |
| PPAR
agonist: | Pioglitazone
(30 mg/day for 6 months) |
| Metabolic
outcomes: | Body
weight, BMI, and WHR increased significantly. Fasting insulin and insulin AUC
during a 2-h OGTT decreased. Insulin resistance decreased and insulin
sensitivity increased after treatment with either pioglitazone or metformin
received by control group. |
| Reproductive
outcomes: | Hirsutism,
free-T and androstenedione declined to a similar extent after treatment with
either drug. Treatment with both drugs was associated with the occurrence of
pregnancy |
|
| Reference: | Sepilian and Nagamani [89] |
| Patient
profile: | Obese
insulin resistant PCOS (n = 12) |
| PPAR
agonist: | Rosiglitazone
(4 mg/day for 6 months) |
| Metabolic
outcomes: | Fasting
insulin, insulin AUC, fasting glucose, and glucose AUC significantly decreased.
No significant change in BMI |
| Reproductive
outcomes: | Both
total-T, free-T and DHEA-S levels decreased significantly. No significant
change in LH levels. Levels of SHBG increased significantly after treatment,
91.7% of women reverted to regular ovulatory cycles during the treatment
period |
|
