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CompletedNCT00529542Updated Sep 25, 2014Results posted

A Trial of Lipitor (Atorvastatin) for the Treatment of Polycystic Ovary Syndrome (PCOS) in Women With Elevated Low-density Lipoprotein (LDL) Cholesterol

A Phase 2 interventional study of Lipitor and Placebo in Polycystic Ovary Syndrome, sponsored by Milton S. Hershey Medical Center. Completed at 1 site in United States. Open to female participants aged 18 Years to 40 Years. Per ClinicalTrials.gov, last updated 2014-09-25.

Sponsored by Milton S. Hershey Medical Center · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
20
Allocation
Randomized
Ages
18 Years to 40 Years
Sex
Female
01

Study summary

The purpose of this study is to determine the efficacy of Lipitor (Atorvastatin) for the treatment of PCOS with elevated LDL cholesterol.

Read the detailed description

The investigators hypothesize that improving the lipid profile with atorvastatin will improve vascular function, increase the frequency of ovulation, decrease androgen levels, improve insulin sensitivity, and improve the lipid profile more efficiently than placebo.

02

Conditions studied

  • Polycystic Ovary Syndrome

Keywords

  • Polycystic Ovary Syndrome
03

In context

Polycystic Ovary Syndrome

944 studies on the registry are indexed under Polycystic Ovary Syndrome; 175 are open to participants now.

This study's enrollment of 20 is below the median of 70 across 685 interventional studies indexed under Polycystic Ovary Syndrome.

Browse Polycystic Ovary Syndrome studies →

Lead sponsor

Milton S. Hershey Medical Center is the lead sponsor of 480 studies on the registry; 61 are open to participants now.

Of its 56 completed or terminated interventional studies of FDA-regulated products, 42 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 40 Years
Sexes eligible
Female
Accepts healthy volunteers
No

Eligibility criteria

Inclusion Criteria: Women with PCOS

  • 8 or fewer menstrual periods per year
  • elevated serum total testosterone
  • elevated LDL cholesterol

Exclusion Criteria:

  • current pregnancy or breastfeeding
  • current use of oral contraceptives, progestins
  • insulin sensitizing medications
  • thyroid disease, hyperprolactinemia, active liver disease, type 1 or type 2 diabetes
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
20 participants (actual)

Study arms

  • Experimental
    Atorvastatin

    Drug: Lipitor

  • Placebo comparator
    Placebo

    Drug: Placebo

Interventions

  • DrugLipitor

    40mg caplets per day for six weeks

    Also known as: Atorvastatin

  • DrugPlacebo

    1 placebo caplet per day for six weeks.

    Also known as: Sugar Pill

06

What researchers measure

Primary outcomes

  1. Brachial Artery Flow-mediated Dilation (FMD)

    Brachial artery FMD, the percent change in brachial artery diameter following release of transient occlusion, was selected as the primary outcome because it is the most widely used research tool for evaluating the effects of interventions on endothelial function. FMD has been shown to predict longterm cardiovascular events, even in patients with no apparent heart disease.

    Time frame: baseline and 6 weeks

Secondary outcomes

  1. Peak Brachial Artery Conductance (BAC)

    Pneumatic cuffs were positioned on the upper arm and wrist of the experimental arm. The brachial artery was imaged using an ATL Doppler ultrasound probe (5-12MHz linear array scanhead, HDI 5000, Advanced Technology Laboratories, Bothell, WA). Mean blood flow velocity (MBV) and brachial artery diameter (BAD) were recorded at baseline. Then the wrist cuff was inflated to 200-250 mmHg. After a minute, with the wrist cuff still inflated, the arm cuff was inflated to 200-250 mmHg. After 10 minutes the arm cuff was released to induce reactive hyperemia in the brachial artery. Upon release of the arm cuff, we continuously measured blood pressure (BP), heart rate (HR), and MBV, and intermittently measured BAD in the experimental arm. Brachial artery conductance (BAC)was calculated as MBV/MAP and FMD was calculated as percent change in BAD from baseline.

    Time frame: baseline and 6 weeks

  2. Total Cholesterol

    Time frame: baseline and 6 weeks

  3. LDL Cholesterol

    Time frame: baseline and 6 weeks

  4. HDL Cholesterol

    Time frame: baseline and 6 weeks

  5. Triglycerides

    Time frame: baseline and 6 weeks

  6. Fasting Glucose

    Time frame: baseline and 6 weeks

  7. Fasting Insulin

    Time frame: baseline and 6 weeks

  8. Area Under the Curve (AUC) for Glucose During OGTT

    A 75 gram oral glucose tolerance test (OGTT) was performed with blood draws at 0, 30, 60, 90 and 120 minutes.

    Time frame: baseline and 6 weeks

  9. AUC for Insulin

    Area under the curve for insulin during OGTT: A 75 gram oral glucose tolerance test was performed with blood draws at 0, 30, 60, 90 and 120 minutes.

    Time frame: baseline and 6 weeks

  10. Total Testosterone

    Time frame: baseline and 6 weeks

  11. Androstenedione

    Time frame: baseline and 6 weeks

  12. DHEAS

    Dehydroepiandrosterone sulfate

    Time frame: baseline and 6 weeks

Other outcomes

  1. High-sensitivity C-reactive Protein (hsCRP)

    high sensitive C-reactive protein as a measure of inflammation

    Time frame: baseline and 6 weeks

07

Results

Posted May 8, 2013

Participant flow

Participants were recruited through the clinics of the Departments of Medicine and Obstetrics and Gynecology at Penn State Hershey Medical Center from October 20, 2006 to September 8, 2008.

Participant flow — Overall Study
MilestoneAtorvastatinPlacebo
Started911
Completed810
Not completed11
Withdrew: Withdrawal by subject10
Withdrew: Lost to follow-up01

Outcome measures

PrimaryBrachial Artery Flow-mediated Dilation (FMD)

Brachial artery FMD, the percent change in brachial artery diameter following release of transient occlusion, was selected as the primary outcome because it is the most widely used research tool for evaluating the effects of interventions on endothelial function. FMD has been shown to predict longterm cardiovascular events, even in patients with no apparent heart disease.

Time frame:
baseline and 6 weeks
Reported as:
Mean · % change in brachial artery diameter
Brachial Artery Flow-mediated Dilation (FMD)
% change in brachial artery diameterAtorvastatinPlacebo
Before treatment12.0 ± 7.39.8 ± 5.8
After treatment10.4 ± 4.610.2 ± 2.9
Statistical analysis
  • Atorvastatin vs Placebo · Linear mixed-effects models · p = 0.58 (All hypotheses tests were two-sided.) · Mean difference (net): -2.0 · 95% CI -9.3 to 5.3This analysis revealed that the required sample size was 235 subjects per group for 80% power to detect an absolute 2% increase in FMD with Atorvastatin vs. Placebo. We stopped the trial because we had insufficient funds for the required sample size.
SecondaryPeak Brachial Artery Conductance (BAC)

Pneumatic cuffs were positioned on the upper arm and wrist of the experimental arm. The brachial artery was imaged using an ATL Doppler ultrasound probe (5-12MHz linear array scanhead, HDI 5000, Advanced Technology Laboratories, Bothell, WA). Mean blood flow velocity (MBV) and brachial artery diameter (BAD) were recorded at baseline. Then the wrist cuff was inflated to 200-250 mmHg. After a minute, with the wrist cuff still inflated, the arm cuff was inflated to 200-250 mmHg. After 10 minutes the arm cuff was released to induce reactive hyperemia in the brachial artery. Upon release of the arm cuff, we continuously measured blood pressure (BP), heart rate (HR), and MBV, and intermittently measured BAD in the experimental arm. Brachial artery conductance (BAC)was calculated as MBV/MAP and FMD was calculated as percent change in BAD from baseline.

Time frame:
baseline and 6 weeks
Reported as:
Mean · ml/sec/mm Hg
Peak Brachial Artery Conductance (BAC)
ml/sec/mm HgAtorvastatinPlacebo
Before treatment5.4 ± 2.93.6 ± 3.0
After treatment6.9 ± 2.84.3 ± 3.3
Statistical analysis
  • Atorvastatin vs Placebo · Linear mixed-effects models · p = 0.39 · Mean difference (net): 0.7 · 95% CI -0.9 to 2.3
SecondaryTotal Cholesterol
Time frame:
baseline and 6 weeks
Reported as:
Mean · mg/dl
Total Cholesterol
mg/dlAtorvastatinPlacebo
Before treatment215.8 ± 39.0202.8 ± 28.3
After treatment132.0 ± 19.7192.1 ± 33.6
Statistical analysis
  • Atorvastatin vs Placebo · Linear mixed-effects models · p = <0.001 · Mean difference (net): -70.8 · 95% CI -95.2 to -46.4
SecondaryLDL Cholesterol
Time frame:
baseline and 6 weeks
Reported as:
Mean · mg/dl
LDL Cholesterol
mg/dlAtorvastatinPlacebo
Before treatment140.7 ± 24.6131.3 ± 21.6
After treatment68.5 ± 19.3118.8 ± 26.8
Statistical analysis
  • Atorvastatin vs Placebo · Linear mixed-effects models · p = <0.001 · Mean difference (net): -57.6 · 95% CI -79.3 to -35.9
SecondaryHDL Cholesterol
Time frame:
baseline and 6 weeks
Reported as:
Mean · mg/dl
HDL Cholesterol
mg/dlAtorvastatinPlacebo
Before treatment44.4 ± 14.646.5 ± 8.6
After treatment47.8 ± 11.846.8 ± 8.4
Statistical analysis
  • Atorvastatin vs Placebo · Linear mixed-effects models · p = 0.26 · Mean difference (net): 3.4 · 95% CI -2.7 to 9.5
SecondaryTriglycerides
Time frame:
baseline and 6 weeks
Reported as:
Mean · mg/dl
Triglycerides
mg/dlAtorvastatinPlacebo
Before treatment153.3 ± 84.9125.5 ± 54.2
After treatment78.5 ± 24.8132.5 ± 45.7
Statistical analysis
  • Atorvastatin vs Placebo · Linear mixed-effects models · p = <0.001 · Mean difference (net): -82.2 · 95% CI -126.2 to -38.1
SecondaryFasting Glucose
Time frame:
baseline and 6 weeks
Reported as:
Mean · mg/dl
Fasting Glucose
mg/dlAtorvastatinPlacebo
Before treatment87.7 ± 9.085.3 ± 8.0
After treatment87.8 ± 8.588.9 ± 10.7
Statistical analysis
  • Atorvastatin vs Placebo · Linear mixed-effects models · p = 0.45 · Mean difference (net): -3.3 · 95% CI -12.4 to 5.8
SecondaryFasting Insulin
Time frame:
baseline and 6 weeks
Reported as:
Mean · uU/ml
Fasting Insulin
uU/mlAtorvastatinPlacebo
Before treatment18.6 ± 10.116.8 ± 9.5
After treatment21.0 ± 11.815.9 ± 6.7
Statistical analysis
  • Atorvastatin vs Placebo · Linear mixed-effects models · p = 0.33 · Mean difference (net): 2.5 · 95% CI -2.8 to 7.9
SecondaryArea Under the Curve (AUC) for Glucose During OGTT

A 75 gram oral glucose tolerance test (OGTT) was performed with blood draws at 0, 30, 60, 90 and 120 minutes.

Time frame:
baseline and 6 weeks
Reported as:
Mean · mg*minute/dL
Area Under the Curve (AUC) for Glucose During OGTT
mg*minute/dLAtorvastatinPlacebo
Before treatment15693 ± 216215309 ± 3692
After treatment16136 ± 256915448 ± 3165
Statistical analysis
  • Atorvastatin vs Placebo · Linear mixed-effects models · p = 0.61 · Mean difference (net): 586 · 95% CI -1811 to 2983
SecondaryAUC for Insulin

Area under the curve for insulin during OGTT: A 75 gram oral glucose tolerance test was performed with blood draws at 0, 30, 60, 90 and 120 minutes.

Time frame:
baseline and 6 weeks
Reported as:
Mean · uU*minute/mL
AUC for Insulin
uU*minute/mLAtorvastatinPlacebo
Before treatment12738 ± 100109338 ± 5208
After treatment17479 ± 119299132 ± 4466
Statistical analysis
  • Atorvastatin vs Placebo · Linear mixed-effects models · p = 0.07 · Mean difference (net): 3385 · 95% CI -287 to 7056
SecondaryTotal Testosterone
Time frame:
baseline and 6 weeks
Reported as:
Mean · ng/dl
Total Testosterone
ng/dlAtorvastatinPlacebo
Before treatment61.3 ± 16.992.3 ± 49.8
After treatment47.1 ± 21.475.7 ± 43.6
Statistical analysis
  • Atorvastatin vs Placebo · Linear mixed-effects models · p = 0.88 · Mean difference (net): 1.8 · 95% CI -24.1 to 27.8
SecondaryAndrostenedione
Time frame:
baseline and 6 weeks
Reported as:
Mean · ng/ml
Androstenedione
ng/mlAtorvastatinPlacebo
Before treatment3.4 ± 0.83.8 ± 1.2
After treatment2.5 ± 0.94.1 ± 1.2
Statistical analysis
  • Atorvastatin vs Placebo · Linear mixed-effects models · p = <0.001 · Mean difference (net): -1.1 · 95% CI -1.6 to -0.5
SecondaryDHEAS

Dehydroepiandrosterone sulfate

Time frame:
baseline and 6 weeks
Reported as:
Mean · ng/ml
DHEAS
ng/mlAtorvastatinPlacebo
Before treatment1630.0 ± 873.11701.5 ± 681.3
After treatment1326.4 ± 854.31739.5 ± 781.8
Statistical analysis
  • Atorvastatin vs Placebo · Linear mixed-effects models · p = 0.02 · Mean difference (net): -364.3 · 95% CI -655.3 to -73.2
Other pre-specifiedHigh-sensitivity C-reactive Protein (hsCRP)

high sensitive C-reactive protein as a measure of inflammation

Time frame:
baseline and 6 weeks
Reported as:
Mean · mg/L
High-sensitivity C-reactive Protein (hsCRP)
mg/LAtorvastatinPlacebo
Before treatment8.0 ± 9.67.2 ± 7.7
After treatment4.3 ± 5.46.0 ± 7.3
Statistical analysis
  • Atorvastatin vs Placebo · Linear mixed-effects models · p = 0.21 · Mean difference (net): -2.4 · 95% CI -6.4 to 1.5
Post-hocSystolic Blood Pressure
Time frame:
baseline and 6 weeks
Reported as:
Mean · mm Hg
Systolic Blood Pressure
mm HgAtorvastatinPlacebo
Before treatment119.8 ± 15.8114.5 ± 14.4
After treatment112.0 ± 13.2111.4 ± 8.8
Statistical analysis
  • Atorvastatin vs Placebo · Linear mixed-effects models · p = 0.27 · Mean difference (net): -5.9 · 95% CI -16.9 to 5.0
Post-hocDiastolic Blood Pressure
Time frame:
baseline and 6 weeks
Reported as:
Mean · mm Hg
Diastolic Blood Pressure
mm HgAtorvastatinPlacebo
Before treatment70.8 ± 14.864.6 ± 8.0
After treatment64.3 ± 12.365.4 ± 8.1
Statistical analysis
  • Atorvastatin vs Placebo · Linear mixed-effects models · p = 0.05 · Mean difference (net): -7.8 · 95% CI -15.8 to 0.1
Post-hocMean Ovarian Volume

Pelvic ultrasound was performed using the 6.5 megahertz (MHz) probe of an ATL 400 machine to characterize ovarian size and morphology. Since in vitro studies demonstrate that statins inhibit ovarian theca-interstitial cell proliferation, we hypothesized that statins might reduce ovarian volume in PCOS.

Time frame:
baseline and 6 weeks
Reported as:
Mean · mm3
Mean Ovarian Volume
mm3AtorvastatinPlacebo
Before treatment15.1 ± 8.825.4 ± 13.7
After treatment19.2 ± 7.025.2 ± 9.9
Statistical analysis
  • Atorvastatin vs Placebo · Linear mixed-effects models · p = 0.48 · Mean difference (net): 3.5 · 95% CI -6.8 to 13.7
Post-hocBody Mass Index
Time frame:
baseline and 6 weeks
Reported as:
Mean · kg/m2
Body Mass Index
kg/m2AtorvastatinPlacebo
Before treatment40.1 ± 11.836.0 ± 10.4
After treatment38.2 ± 8.435.8 ± 10.8
Statistical analysis
  • Atorvastatin vs Placebo · Linear mixed-effects models · p = 0.63 · Mean difference (net): 0.2 · 95% CI -0.6 to 1.0

Adverse events

Collected over 6 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Atorvastatin—1/9 (11.1%)1/9 (11.1%)
Placebo—0/11 (0%)2/11 (18.2%)
Most frequent serious events
Most frequent serious events
EventAtorvastatinPlacebo
gallbladder removalHepatobiliary disorders1/90/11
Most frequent other events
Most frequent other events
EventAtorvastatinPlacebo
muscle painMusculoskeletal and connective tissue disorders1/90/11
swellingGeneral disorders0/91/11
headacheNervous system disorders0/91/11

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)AtorvastatinPlaceboTotal
<=18 years000
Between 18 and 65 years91120
>=65 years000
Sex: Female, Male
Sex: Female, Male(Participants)AtorvastatinPlaceboTotal
Female91120
Male000
Region of Enrollment
Region of Enrollment(participants)AtorvastatinPlaceboTotal
United States91120
08

Study locations

1 site
  • Penn State Milton S Hershey Medical Center, College of Medicine
    Hershey, Pennsylvania 17033, United States
09

References and documents

Publications

  • Raja-Khan N, Kunselman AR, Hogeman CS, Stetter CM, Demers LM, Legro RS. Effects of atorvastatin on vascular function, inflammation, and androgens in women with polycystic ovary syndrome: a double-blind, randomized, placebo-controlled trial. Fertil Steril. 2011 Apr;95(5):1849-52. doi: 10.1016/j.fertnstert.2010.11.040. Epub 2010 Dec 8. PubMed 21144505 ↗

Related links

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 25, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00529542
Lead sponsor
Milton S. Hershey Medical Center
Responsible party
Richard S. Legro, M.D. (Professor, Obstetrics and Gynecology and Public Health Sciences, Milton S. Hershey Medical Center) — Principal investigator
First posted
Sep 14, 2007
Start date
Dec 2004
Primary completion
Aug 2010
Completion
Aug 2010
Results posted
May 8, 2013
Last update
Sep 25, 2014

Study contacts

Richard S Legro, MD
principal investigator · Penn State College of Medicine

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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