Androgen Excess, Irregular Menstrual Cycles, Polycystic Ovarian Syndrome (PCOS)
Conditions
Keywords
Polycystic Ovarian Syndrome, Irregular Menstrual Cycles, Androgen Excess in Women
Brief summary
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
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.
Interventions
DRUGdoxycycline
200mg/day in divided doses of 100mg twice daily
OTHERSugar Pill
1 pill twice a day
Sponsors
University of Rochester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
1. Women between 18 and 40 years of age. 2. History of PCOS with \< 8 periods the proceeding year 3. Clinical or biochemical evidence of androgen excess 4. BMI \<40 5. Willingness to sign consent for study including participation with collection of blood specimens 6. Willingness to discontinue OCP for duration of study period up to 36 weeks
Exclusion criteria
1. Pregnancy 2. Hypersensitivity to doxycycline or tetracycline 3. History of Cushing's syndrome 4. History of hyperprolactinemia 5. History of congenital adrenal hyperplasia 6. Significant hepatic impairment, including serum AST or ALT \>1.5 times upper limits of normal. 7. Significant renal impairment, GFR \<60 ml/min 8. Current use of metformin, statins, glucocorticoids, spironolactone and/or anti-estrogens.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Serum Testosterone | 24 weeks | We will determine total serum testosterone levels in all participating subjects at week 24. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Progesterone Levels in Blood | 24 weeks | 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. |
| Free Testosterone in Serum | week 12 | — |
| Serum Hormone Binding Globulin (SHBG) | week 12 | — |
| Total Number of Ovulations | week 24 | 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. |
Countries
United States
Participant flow
Recruitment details
13 women were recruited. 3 did not meet inclusion/esclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Doxycycline 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.
doxycycline: 200mg/day in divided doses of 100mg twice daily | 5 |
| Sugar Pill The administered placebo is to be continued for a period of 12 weeks. A 12-week period thereafter will occur off placebo control
Sugar Pill: 1 pill twice a day | 5 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Doxycycline | Sugar Pill | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 5 Participants | 10 Participants |
| free serum testosterone | 1.14 pg/mL STANDARD_DEVIATION 0.57 | 1.36 pg/mL STANDARD_DEVIATION 0.39 | 1.25 pg/mL STANDARD_DEVIATION 0.48 |
| Region of Enrollment United States | 5 participants | 5 participants | 10 participants |
| serum hormone binding globulin (SHBG) | 55.0 nmol/L STANDARD_DEVIATION 13.2 | 44.0 nmol/L STANDARD_DEVIATION 13.5 | 49.5 nmol/L STANDARD_DEVIATION 13.4 |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| total serum testosterone | 50.6 ng/dL STANDARD_DEVIATION 8.2 | 49.6 ng/dL STANDARD_DEVIATION 8.2 | 50.1 ng/dL STANDARD_DEVIATION 8.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 5 | 0 / 5 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 |
Outcome results
Primary
Total Serum Testosterone
We will determine total serum testosterone levels in all participating subjects at week 12.
Time frame: week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Doxycycline | Total Serum Testosterone | 49.4 ng/dL | Standard Deviation 10.8 |
| Sugar Pill | Total Serum Testosterone | 43.0 ng/dL | Standard Deviation 8.6 |
Primary
Total Serum Testosterone
We will determine total serum testosterone levels in all participating subjects at week 24.
Time frame: 24 weeks
Population: in the sugar pill arm one participant dropped out at week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Doxycycline | Total Serum Testosterone | 61.8 ng/dL | Standard Deviation 13.6 |
| Sugar Pill | Total Serum Testosterone | 41.6 ng/dL | Standard Deviation 9.8 |
Secondary
Free Testosterone in Serum
Time frame: week 24
Population: in the sugar till arm, one participant dropped out at week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Doxycycline | Free Testosterone in Serum | 1.76 pg/mL | Standard Deviation 1.56 |
| Sugar Pill | Free Testosterone in Serum | 1.08 pg/mL | Standard Deviation 0.27 |
Secondary
Free Testosterone in Serum
Time frame: week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Doxycycline | Free Testosterone in Serum | 1.12 pg/mL | Standard Deviation 0.39 |
| Sugar Pill | Free Testosterone in Serum | 1.16 pg/mL | Standard Deviation 0.25 |
Secondary
Serum Hormone Binding Globulin (SHBG)
Time frame: week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Doxycycline | Serum Hormone Binding Globulin (SHBG) | 50.4 nmol/L | Standard Deviation 12.4 |
| Sugar Pill | Serum Hormone Binding Globulin (SHBG) | 39.4 nmol/L | Standard Deviation 10.9 |
Secondary
Serum Hormone Binding Globulin (SHBG)
Time frame: week 24
Population: in the sugar pill arm, one participant withdrew at week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Doxycycline | Serum Hormone Binding Globulin (SHBG) | 44.8 nmol /L | Standard Deviation 10.6 |
| Sugar Pill | Serum Hormone Binding Globulin (SHBG) | 36.2 nmol /L | Standard Deviation 6.75 |
Secondary
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.
Time frame: 24 weeks
Population: This measurement was not completed, because the number of ovulations was measured in its place and better indicates the effect of the treatment. See outcome measure number 8.
Secondary
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.
Time frame: week 24
Population: In the sugar pill arm, one participant withdrew at week 12.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doxycycline | Total Number of Ovulations | 12 ovulations |
| Sugar Pill | Total Number of Ovulations | 7 ovulations |