Effect of a Commonly Used Antibiotic, Doxycycline, in Women With Polycystic Ovarian Syndrome

Study Overview
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Brief Summary
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The purpose of this study is to study the effect of a commonly used antibiotic, doxycycline, on the production of ovarian hormones and menstrual cycles in women with Polycystic Ovarian Syndrome (PCOS).

Detailed Description
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Polycystic ovarian syndrome (PCOS) is one of the leading causes of female infertility, affecting 5-10% of reproductive-age women . This heterogeneous disorder is characterized by anovulatory infertility, androgen excess, an increase in the ratio of LH to FSH, and morphologic polycystic changes to the ovaries. Obesity and insulin resistance are also metabolic factors associated with PCOS that further increase the morbidity in these patients. Inducing fertility in patients with PCOS can be a challenge, as it most often involves ovulation induction that can lead to ovarian enlargement, hyperstimulation, and multiple-birth pregnancies. This study is designed to determine novel effective strategies to promote normal cycling in this patient population.

Official Title
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The Use of an MMP Inhibitor, Doxycycline, to Reduce Ovarian Androgen Production and Restore Normal Cycling in Women With Polycystic Ovarian Syndrome

Conditions
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Polycystic Ovarian Syndrome (PCOS), Irregular Menstrual Cycles, Androgen Excess

Intervention / Treatment
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* Drug: doxycycline
* Other: Sugar Pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women between 18 and 40 years of age. History of PCOS with < 8 periods the proceeding year Clinical or biochemical evidence of androgen excess BMI <40 Willingness to sign consent for study including participation with collection of blood specimens Willingness to discontinue OCP for duration of study period up to 36 weeks Exclusion Criteria: Pregnancy Hypersensitivity to doxycycline or tetracycline History of Cushing's syndrome History of hyperprolactinemia History of congenital adrenal hyperplasia Significant hepatic impairment, including serum AST or ALT >1.5 times upper limits of normal. Significant renal impairment, GFR <60 ml/min Current use of metformin, statins, glucocorticoids, spironolactone and/or anti-estrogens.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Doxycycline<br>Subjects randomized to receive doxycycline for a period of 12 weeks. A 12-week period thereafter will occur off study medication. The dose of doxycycline to be used in this study is 200mg/day in divided doses of 100mg twice daily. The dose of doxycycline being used in this study is 100mg because it is the standard approved dose. | Drug: doxycycline<br>* 200mg/day in divided doses of 100mg twice daily<br>|
| Placebo Comparator: Sugar Pill<br>The administered placebo is to be continued for a period of 12 weeks. A 12-week period thereafter will occur off placebo control | Other: Sugar Pill<br>* 1 pill twice a day<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Serum Testosterone | We will determine total serum testosterone levels in all participating subjects at week 24. | 24 weeks | 
| Total Serum Testosterone | We will determine total serum testosterone levels in all participating subjects at week 12. | week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Progesterone Levels in Blood | Serum progesterone levels will be obtained on a weekly basis to assess ovulation. We will then perform statistical analysis on this data to determine the effectiveness of doxycycline in this study population. | 24 weeks | 
| Free Testosterone in Serum |  | week 12 | 
| Free Testosterone in Serum |  | week 24 | 
| Serum Hormone Binding Globulin (SHBG) |  | week 12 | 
| Serum Hormone Binding Globulin (SHBG) |  | week 24 | 
| Total Number of Ovulations | The total number of ovulations per group. Ovulation was defined as elevation of serum progesterone and or urinary pregnanediol glucuronide followed by documented menstrual bleeding within 2 weeks of elevation. | week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polycystic Ovarian Syndrome, Irregular Menstrual Cycles, Androgen Excess in Women