Influence of Hyperandrogenemia on the Sleep-associated Slowing of Follicular LH Frequency in Adult Polycystic Ovary Syndrome

14067

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.

2009-01-01

2024-05-01

2024-08-01

Active (not recruiting)

Early phase I

72

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.

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2023-11-02