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The mainstay treatment for females with Polycystic Ovary Syndrome (PCOS) has long been a combination of an oral contraceptive pill or OCP (containing both estrogen and progestin) along with an anti-androgen medication (such as Spironolactone) to not only prevent chronic anovulation but also suppress elevated testosterone levels and its clinical effects on the body. While there are multiple OCPs available on the market today and several studies that look at different progestins and their anti-androgenicity, not much is known about whether the length of active pills in OCP therapy (3 weeks versus 6 months) has any further benefit in continued suppression of testosterone and subsequently improvement in clinical findings of hyperandrogenism in the PCOS population. In this pilot randomized open label clinical trial, females between the ages of 16 and 35 years diagnosed with PCOS based on the Rotterdam Criteria, and not currently on medical therapy with an OCP will be enrolled in the study and randomized to either a continuous 6 month OCP or cyclical 21 day active OCP therapy. Our aim is to conduct a pilot randomized clinical trial to determine the effect of 6 months of active monophasic OCPs on testosterone levels and cutaneous findings of hyperandrogenism (hirsutism and acne) as compared to a traditional 21 day active/7 day placebo OCP in women with PCOS. These findings will be compared over a 6 month period.
Those who meet criteria to take part in the study (women between the ages of 16-35 years, diagnosed with PCOS and have findings of hyperandrogenism either by serum testosterone levels above the normal reference range or by their modified Ferriman Gallwey score of >8, and are recommended to start an oral contraceptive pill for therapy) and give consent, will be randomized into either of two oral contraceptive (OCP) treatment groups:
Participants will be given the OCP Yasmin with instructions to take the medication at the same time each day for the length of the study (6 months). On the 4th, 12th and 24th week of therapy (roughly the 1st, 3rd and 6th month), blood work will be drawn and is detailed below.
At 1 month into therapy, (near the end of the 4th week on an OCP) both treatment groups will be expected to get blood work (total and free testosterone, SHBG, estradiol, LH, and FSH levels will be checked). At the time of the blood draw, subjects in the cyclical group should be on placebo/sugar pills and those in the continuous group on active hormone pills.
At 3 months into therapy, participants will come back to the PCOS clinic for routine care follow up and be seen by a Reproductive Endocrinology and Fertility specialist. This visit is considered "standard of care" and not specific to the study. However, during this visit a study investigator will also touch base briefly with the participants to see how they are doing. An online survey (through REDCap) will also be sent to participants that addresses if they have missed any doses of their medication and assess their acne quality of life. In addition, participants will once again get blood work (including total and free testosterone, SHBG, estradiol, LH, FSH, fasting lipid panel, fasting serum glucose, insulin, and HbA1c). As before, the cyclical group should be on placebo/sugar pills at the time of blood draw and the continuous group on active hormone pills.
At 6 months into therapy, participants will come in for a study visit (this is not considered routine care) in which they will have their vitals taken, a physical exam that includes a re-evaluation of their mFG score, and an in-clinic pelvic ultrasound to assess ovarian volume and follicle counts. They will also be emailed a post-study survey through REDCap, that includes a quality of life questionnaire for both acne and hirsutism, and includes questions regarding satisfaction with current therapy and any missed doses of their medication. Lastly, participants will again be expected to get blood work (total and free testosterone, SHBG, estradiol, LH, FSH).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Continuous OCP Therapy | Active Comparator | Participants randomly assigned to this arm will receive 8 packs of a 21 day oral contraceptive pills (OCP) called Yasmin (3 mg Drospirenone/0.03 mg Ethinyl estradiol) which comes in a formulation of 21 days of active hormone and 7 days of sugar pills. In this arm, participants will only be expected to take active hormone pills (colored pills) for the 6 months straight without stopping or taking the sugar pills in each pack. |
|
| Cyclical OCP Therapy | Active Comparator | Participants randomly assigned to this arm will receive 6 packs of a 21 day oral contraceptive pill (OCP) called Yasmin (3 mg Drospirenone/0.03 mg Ethinyl estradiol) which has 21 days of active hormone and 7 days of sugar pills. Participants will take one pill daily for 6 months and be expected to take the sugar pills at the end of each monthly pack prior to starting a new pack. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Yasmin | Drug | Participants in each treatment arm will receive the medication Yasmin. However only the Cyclical OCP Therapy arm will take the sugar pills designated each month in the pill packs and the Continuous OCP Therapy arm will not. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Biochemical Hyperandrogenism From Baseline to 1 Month Post Yasmin Initiation | Positive or negative change in blood serum Total Testosterone value (units: ng/dl) from baseline to 1 month post Yasmin initiation. | measured at baseline and 1 month into therapy |
| Change in Biochemical Hyperandrogenism From Baseline to 3 Month Post Yasmin Initiation | Positive or negative change in blood serum Total Testosterone value (units: ng/dl) from baseline to 3 month post Yasmin initiation. | measured at baseline and 3 month into therapy |
| Change in Biochemical Hyperandrogenism From Baseline to 6 Month Post Yasmin Initiation | Positive or negative change in blood serum Total Testosterone value (units: ng/dl) from baseline to 6 month post Yasmin initiation. | measured at baseline and 6 month into therapy |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Clinical Findings of Hyperandrogenism - Hirsutism | Participants will be examined by a physician and scored using the modified Ferriman-Gallwey Hirsutism score (mFG). This scoring system is considered the standard scoring system that defines hirsutism (excess male pattern hair growth on the body) quantitatively. There are 9 body areas measured on a scare of 0-4, with higher values indicative of significant hair growth. All subscales are combined for a total score, with a minimum score of 0 and max of 36. A total score of >/=8 is considered diagnostic for hirsutism. The difference in score values from baseline to 6 months was then calculated. |
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Inclusion Criteria: To be included in this study, participants must be:
Female, within 15-40 years of age
Diagnosed with Polycystic Ovary Syndrome based on the 2003 Rotterdam Criteria (must meet 2 out of 3 criteria):
Adolescents should be at least 2 years out from menarche (first menstrual period).
Participants must not be on an oral contraceptive pill (OCP) at the start of the study and or Spironolactone therapy (an anti-androgen medication), but recommended by their physician to start OCP therapy.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Heather Huddleston, MD | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, San Francisco | San Francisco | California | 94158 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18056769 | Background | Legro RS, Pauli JG, Kunselman AR, Meadows JW, Kesner JS, Zaino RJ, Demers LM, Gnatuk CL, Dodson WC. Effects of continuous versus cyclical oral contraception: a randomized controlled trial. J Clin Endocrinol Metab. 2008 Feb;93(2):420-9. doi: 10.1210/jc.2007-2287. Epub 2007 Dec 4. |
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Enrollment occurred between April 2019 and January 2022 at the UCSF Center for Reproductive Health's PCOS multidisciplinary clinic.
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| ID | Title | Description |
|---|---|---|
| FG000 | Continuous OCP Therapy | Participants randomly assigned to this arm will receive 8 packs of a 21 day oral contraceptive pills (OCP) called Yasmin (3 mg Drospirenone/0.03 mg Ethinyl estradiol) which comes in a formulation of 21 days of active hormone and 7 days of sugar pills. In this arm, participants will only be expected to take active hormone pills (colored pills) for the 6 months straight without stopping or taking the sugar pills in each pack. Yasmin: Participants in each treatment arm will receive the medication Yasmin. However only the Cyclical OCP Therapy arm will take the sugar pills designated each month in the pill packs and the Continuous OCP Therapy arm will not. |
| FG001 | Cyclical OCP Therapy | Participants randomly assigned to this arm will receive 6 packs of a 21 day oral contraceptive pill (OCP) called Yasmin (3 mg Drospirenone/0.03 mg Ethinyl estradiol) which has 21 days of active hormone and 7 days of sugar pills. Participants will take one pill daily for 6 months and be expected to take the sugar pills at the end of each monthly pack prior to starting a new pack. Yasmin: Participants in each treatment arm will receive the medication Yasmin. However only the Cyclical OCP Therapy arm will take the sugar pills designated each month in the pill packs and the Continuous OCP Therapy arm will not. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Continuous OCP Therapy | Participants randomly assigned to this arm will receive 8 packs of a 21 day oral contraceptive pills (OCP) called Yasmin (3 mg Drospirenone/0.03 mg Ethinyl estradiol) which comes in a formulation of 21 days of active hormone and 7 days of sugar pills. In this arm, participants will only be expected to take active hormone pills (colored pills) for the 6 months straight without stopping or taking the sugar pills in each pack. Yasmin: Participants in each treatment arm will receive the medication Yasmin. However only the Cyclical OCP Therapy arm will take the sugar pills designated each month in the pill packs and the Continuous OCP Therapy arm will not. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Biochemical Hyperandrogenism From Baseline to 1 Month Post Yasmin Initiation | Positive or negative change in blood serum Total Testosterone value (units: ng/dl) from baseline to 1 month post Yasmin initiation. | Analysis exclusions: 1 non-compliant initially with taking continuous dose, 1 unable to promptly obtain yasmin from pharmacy, 1 unresponsive to appointment scheduling reminders, 6 insufficient specimen volume to run assay and unable to calculate change value. | Posted | Mean | Standard Deviation | ng/dl | measured at baseline and 1 month into therapy |
|
6 months while on Yasmin
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Continuous OCP Therapy | Participants randomly assigned to this arm will receive 8 packs of a 21 day oral contraceptive pills (OCP) called Yasmin (3 mg Drospirenone/0.03 mg Ethinyl estradiol) which comes in a formulation of 21 days of active hormone and 7 days of sugar pills. In this arm, participants will only be expected to take active hormone pills (colored pills) for the 6 months straight without stopping or taking the sugar pills in each pack. Yasmin: Participants in each treatment arm will receive the medication Yasmin. However only the Cyclical OCP Therapy arm will take the sugar pills designated each month in the pill packs and the Continuous OCP Therapy arm will not. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Undisclosed Exclusion Criteria - Symptoms and History of Migraines with Aura | Nervous system disorders | Non-systematic Assessment | More serious than expected, possibly related to study. PI removed the participant from the study by having her stop the OCP due to the severe migraines with aura that she was having on 2/2/2021. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Heather Huddleston | University of California, San Francisco | (415) 353-7475 | Heather.Huddleston@ucsf.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 24, 2021 | Oct 17, 2023 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jan 18, 2022 | Oct 17, 2023 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D011085 | Polycystic Ovary Syndrome |
| D017588 | Hyperandrogenism |
| ID | Term |
|---|---|
| D010048 | Ovarian Cysts |
| D003560 | Cysts |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 |
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| ID | Term |
|---|---|
| C534342 | drospirenone and ethinyl estradiol combination |
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| Baseline and at 6 months into therapy |
| Metabolic Changes With OCP Therapy | Diabetes risk will be assessed and compared in both treatment arms by measuring HOMA-IR (calculated as [glucose*insulin]/405) at both baseline and 3 months visits and calculating the change in HOMA-IR value. Higher HOMA-IR values indicate more severe insulin resistance, with the ranges being as follows: HOMA <2: Normal, HOMA 2-4: Mild Insulin Resistance, and HOMA >4: Moderate-Severe Insulin Resistance. | Baseline and at 3 months into therapy |
| Adverse Event |
|
| Unable to attend visit(s) due to contracting COVID |
|
| Unable to attend visit(s) due to UCSF pandemic policies restricting non-essential visits |
|
| BG001 | Cyclical OCP Therapy | Participants randomly assigned to this arm will receive 6 packs of a 21 day oral contraceptive pill (OCP) called Yasmin (3 mg Drospirenone/0.03 mg Ethinyl estradiol) which has 21 days of active hormone and 7 days of sugar pills. Participants will take one pill daily for 6 months and be expected to take the sugar pills at the end of each monthly pack prior to starting a new pack. Yasmin: Participants in each treatment arm will receive the medication Yasmin. However only the Cyclical OCP Therapy arm will take the sugar pills designated each month in the pill packs and the Continuous OCP Therapy arm will not. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Serum Total Testosterone | Mean | Standard Deviation | ng/dl |
|
| Modified Ferriman-Gallwey (mFG) score | Mean | Standard Deviation | units on a scale |
|
| OG001 | Cyclical OCP Therapy | Participants randomly assigned to this arm will receive 6 packs of a 21 day oral contraceptive pill (OCP) called Yasmin (3 mg Drospirenone/0.03 mg Ethinyl estradiol) which has 21 days of active hormone and 7 days of sugar pills. Participants will take one pill daily for 6 months and be expected to take the sugar pills at the end of each monthly pack prior to starting a new pack. Yasmin: Participants in each treatment arm will receive the medication Yasmin. However only the Cyclical OCP Therapy arm will take the sugar pills designated each month in the pill packs and the Continuous OCP Therapy arm will not. |
|
|
| Primary | Change in Biochemical Hyperandrogenism From Baseline to 3 Month Post Yasmin Initiation | Positive or negative change in blood serum Total Testosterone value (units: ng/dl) from baseline to 3 month post Yasmin initiation. | Analysis exclusions: 3 unable to attend appointment due to COVID, 3 participants elected to drop out of study as desired to switch to another brand of OCP, 3 participants were unresponsive to communications to schedule appointment. 4 contracted COVID or unable to attend visit due to UCSF restriction on non-essential visits during COVID lockdown | Posted | Mean | Standard Deviation | ng/dl | measured at baseline and 3 month into therapy |
|
|
|
| Primary | Change in Biochemical Hyperandrogenism From Baseline to 6 Month Post Yasmin Initiation | Positive or negative change in blood serum Total Testosterone value (units: ng/dl) from baseline to 6 month post Yasmin initiation. | Analysis exclusions (16): 3 voluntarily dropped out of study for personal reasons, 3 unresponsive to appointment scheduling reminders,1 broke fast and unable to draw, 1 specimen hemolyzed and unable to run assay, 4 contracted COVID or unable to attend visit due to UCSF restriction on non-essential visits during COVID lockdown,4 insufficient specimen volume to run 6 month assay and unable to calculate change value. | Posted | Mean | Standard Deviation | ng/dl | measured at baseline and 6 month into therapy |
|
|
|
| Secondary | Change in Clinical Findings of Hyperandrogenism - Hirsutism | Participants will be examined by a physician and scored using the modified Ferriman-Gallwey Hirsutism score (mFG). This scoring system is considered the standard scoring system that defines hirsutism (excess male pattern hair growth on the body) quantitatively. There are 9 body areas measured on a scare of 0-4, with higher values indicative of significant hair growth. All subscales are combined for a total score, with a minimum score of 0 and max of 36. A total score of >/=8 is considered diagnostic for hirsutism. The difference in score values from baseline to 6 months was then calculated. | Analysis exclusions: 8 of the 35 participants who attended the 6 month visit declined the physical exam necessary for physician mFG scoring and thus changes in mFG scores from baseline to 6 months could not be calculated for these participants. | Posted | Mean | Standard Deviation | numerical change in score on a scale | Baseline and at 6 months into therapy |
|
|
|
| Secondary | Metabolic Changes With OCP Therapy | Diabetes risk will be assessed and compared in both treatment arms by measuring HOMA-IR (calculated as [glucose*insulin]/405) at both baseline and 3 months visits and calculating the change in HOMA-IR value. Higher HOMA-IR values indicate more severe insulin resistance, with the ranges being as follows: HOMA <2: Normal, HOMA 2-4: Mild Insulin Resistance, and HOMA >4: Moderate-Severe Insulin Resistance. | Posted | Mean | Standard Deviation | HOMA-IR value | Baseline and at 3 months into therapy |
|
|
|
| 0 |
| 26 |
| 0 |
| 26 |
| 0 |
| 26 |
| EG001 | Cyclical OCP Therapy | Participants randomly assigned to this arm will receive 6 packs of a 21 day oral contraceptive pill (OCP) called Yasmin (3 mg Drospirenone/0.03 mg Ethinyl estradiol) which has 21 days of active hormone and 7 days of sugar pills. Participants will take one pill daily for 6 months and be expected to take the sugar pills at the end of each monthly pack prior to starting a new pack. Yasmin: Participants in each treatment arm will receive the medication Yasmin. However only the Cyclical OCP Therapy arm will take the sugar pills designated each month in the pill packs and the Continuous OCP Therapy arm will not. | 0 | 25 | 1 | 25 | 0 | 25 |
|
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| Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D006058 | Gonadal Disorders |
| D004700 | Endocrine System Diseases |
| D058489 | 46, XX Disorders of Sex Development |
| D012734 | Disorders of Sex Development |
| D014564 | Urogenital Abnormalities |
| D047808 | Adrenogenital Syndrome |
| D052801 | Male Urogenital Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |