Effect of High Testosterone on Sleep-associated Slowing of Follicular Luteinizing Hormone (LH) Frequency in Polycystic Ovary Syndrome

• Status: Active, not recruiting
• Trial end date: 2021-07-01
• Target enrollment: 0
• Participant gender: Female

Summary

The purpose of this study is to determine whether a testosterone receptor blocker (flutamide) will normalize sleep-wake luteinizing hormone pulse frequency relationships in women with polycystic ovary syndrome.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Virginia
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Treatments: Flutamide; Testosterone

Criteria

Inclusion Criteria:

Inclusion criteria for all participants:

• Subjects will be 18-35 years old; we use a cutoff age of 35 y because early menopause at this age is very rare.

• No significant health problems (other than PCOS and obesity).

• Subjects will be willing to strictly avoid pregnancy (using non-hormonal methods) during the time of study and must be willing and able to provide informed consent.

Inclusion criteria for normal controls:

• Controls will be healthy women with regular menstrual cycles and no evidence of hyperandrogenism.

Inclusion criteria for PCOS:

• PCOS will be defined according to NIH consensus criteria.

• As such, subjects with PCOS will have hyperandrogenism, whether it is clinical (e.g., hirsutism) or biochemical (i.e., elevated plasma T).

• Subjects with PCOS will also have oligo- or amenorrhea (i.e., < 7 periods per year) and no evidence for other endocrinopathies (e.g., hyperprolactinemia, Cushing's syndrome, etc.).

Exclusion Criteria:

• Being a study of GnRH pulse regulation in women with and without PCOS, men are excluded.

• Obesity associated with a diagnosed (genetic) syndrome, obesity related to medications (e.g., glucocorticoids), etc.

• Pregnancy or lactation.

• Virilization.

• A total testosterone > 150 ng/dl in women with PCOS (which suggests the possibility of a virilizing neoplasm) (confirmed on repeat).

• Elevated DHEAS (mild elevations may be seen in PCOS, and elevations < 1.5 times the upper limit of normal will be accepted in PCOS)(confirmed on repeat).

• Follicular 17-hydroxyprogesterone > 300 ng/dl, which suggests the possibility of congenital adrenal hyperplasia (if elevated during the luteal phase and there is a concern about the possibility of congenital adrenal hyperplasia, the 17-hydroxyprogesterone may be collected during the follicular phase, or >60 if oligomenorrheic).

*NOTE: If a 17-hydroxyprogesterone > 300 ng/dl is confirmed on such repeat testing, an ACTH stimulated 17-hydroxyprogesterone < 1000 ng/dl will be required for study participation.

• A previous diagnosis of diabetes, a fasting glucose ≥ 126 mg/dl, or a hemoglobin A1c > 6.5%

• Abnormal TSH (subjects with adequately treated hypothyroidism, reflected by normal TSH values, will not be excluded; or, for a new diagnosis of hypothyroidism, further study will at the least be delayed pending appropriate treatment) (confirmed on repeat).

• Abnormal prolactin (mild elevations may be seen in PCOS, and elevations < 1.5 times the upper limit of normal will be accepted in this group) (confirmed on repeat).

• Evidence of Cushing's syndrome by history or physical exam.

• Hematocrit < 36% or hemoglobin < 12 g/dl (that is not reversed by iron treatment).

• Significant history of cardiac or pulmonary dysfunction (e.g., known or suspected congestive heart failure; asthma requiring intermittent systemic corticosteroids; etc.)

• Liver test abnormalities (confirmed on repeat), with the exception that mild bilirubin elevations will be accepted in the setting of known Gilbert's syndrome.

• Abnormal sodium or potassium (confirmed on repeat); bicarbonate concentration <20 or >30 (confirmed on repeat); or elevated creatinine concentration (confirmed on repeat).

• Due to the amount of blood being drawn in the study, subjects with body weight < 110 lbs will be excluded from the study.