Clinical trial NCT01154192: Theca Cell Function in Adolescents With Polycystic Ovary Syndrome (PCOS)
Official title: Theca Cell Function in Adolescents With Polycystic Ovary Syndrome (PCOS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: PCOS
Keywords: PCOS
oligomenorrhea
irregular menses
hyperandrogenemia
elevated testosterone
adolescents
androgens
ovary
LH
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: University of Virginia
First posted: 2010-06-30
Enrollment: 24
Sex: FEMALE
Minimum age (years): 12
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: In women with polycystic ovary syndrome (PCOS), the cardinal physiological abnormality is excessive ovarian androgen production marked by increased serum testosterone (T) and androstenedione (A) levels. Studies to determine the alteration in ovarian steroidogenesis that lead to abnormal production of ovarian androgens have revealed increased CYP17 gene expression with accentuated 17-hydroxylase activity leading to exaggerated 17-hydroxyprogesterone (17P) responses to luteinizing hormone (LH) stimulation. In contrast, T and A responses did not distinguish between PCOS and normal women, although these androgens were clearly greater in the former compared to the latter group. As a result, 17P responsiveness has been employed to determine the functional capacity of the ovary to produce androgens. The stimulatory agents that have been used included GnRH agonist, Lupron, at a dose of 10 microgram per kilogram, or hCG at a dose of 10,000 IU. The investigators propose to conduct a study that will determine the pattern of androgen responsiveness to 25ucg of hCG after 24 hours in adolescents with PCOS, those with oligomenorrhea, and in normal controls. This will allow for a comparison of these adolescents' ovarian functional capacity to produce androgens.

Detailed description: In women with polycystic ovary syndrome (PCOS), the cardinal physiological abnormality is excessive ovarian androgen production marked by increased serum testosterone (T) and androstenedione (A) levels. Studies to determine the alteration in ovarian steroidogenesis that lead to abnormal production of ovarian androgens have revealed increased CYP17 gene expression with accentuated 17-hydroxylase activity leading to exaggerated 17-hydroxyprogesterone (17P) responses to luteinizing hormone (LH) stimulation. In contrast, T and A responses did not distinguish between PCOS and normal women, although these androgens were clearly greater in the former compared to the latter group. As a result, 17P responsiveness has been employed to determine the functional capacity of the ovary to produce androgens. The stimulatory agents that have been used included GnRH agonist, Lupron, at a dose of 10 microgram per kilogram, or hCG at a dose of 10,000 IU.We propose to conduct a study that will determine the pattern of androgen responsiveness to 25ucg of hCG after 24 hours in adolescents with PCOS, those with oligomenorrhea, and in normal controls. This will allow for a comparison of these adolescents' ovarian functional capacity to produce androgens.

Eligibility criteria: Inclusion Criteria:

* Normal CBC (Hemoglobin must be at least 11mg/dl)
* Normal renal and liver function tests
* Normal vital signs including normal blood pressure

Exclusion Criteria:

* Pregnancy
* On oral contraceptives
* On insulin lowering drugs
* On anti-androgens (i.e., spironolactone, flutamide, finasteride, etc)
* On medications that will influence androgen metabolism or clearance
* On medications that will inhibit the cytochrome P450 enzyme system (Cimetidine, ketoconazole, etc)

Primary outcomes:
measure: 17OHP Levels After hCG
timeFrame: 24 hours
Secondary outcomes:
measure: Testosterone
timeFrame: 24 hours
measure: Androstenedione
timeFrame: 24 hours
measure: DHEA
timeFrame: 24 hours
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UCSD School of Medicine
state: California
Study officials:
affiliation: UCSD School of Medicine
name: R. Jeffery Chang, M.D.
role: PRINCIPAL_INVESTIGATOR
References: