Clinical trial: Relative Contributions of Predictors of Hyperandrogenism in Older vs. Young Women With PCOS (NCT03905603)

Eligibility criteria:
Inclusion Criteria:

          -  Women with PCOS aged 20-30 years and 40-49 years. Subject is considered to have PCOS
             if she has current or verifiable history of: a) clinical and/or biochemical evidence
             of hyperandrogenism plus b) oligomenorrhea (average menstrual cycle length >45 days or
             fewer than 9 menses/year) or irregular menstruation (substantially inconsistent
             menstrual cycle length). Note: For subjects aged 40-49 years, they will be allowed to
             participate if they have fewer than 10 menses/year (average menstrual cycle length >35
             days) as long as they have a compelling past history of oligomenorrhea or irregular
             menstruation.

          -  Screening safety labs within normal reference ranges although mild abnormalities that
             are common in obesity and/or hyperandrogenism will not be grounds for exclusion (see
             exclusion criteria).

          -  Subjects must be willing and able to provide written informed consent.

          -  Willingness to strictly avoid pregnancy (using non-hormonal methods) during the time
             of the study

          -  Willingness and ability to comply with scheduled visits and study procedures

        Exclusion Criteria:

          -  Postmenopausal status (i.e., absence of periods for previous year plus elevated
             follicle stimulating hormone [FSH] level)

          -  Biochemical evidence for perimenopause as defined by an anti-Mullerian hormone <0.5
             ng/mL. As an alternative, cycle day 3 FSH > 9 IU/L (with concomitant estradiol level
             >80 pg/mL), if this testing is available, will serve as evidence of perimenopause
             status. NOTE: If FSH >9 IU/L on screening (but it is not cycle day 3), FSH and
             estradiol will be repeated on cycle day 3.

          -  History of hysterectomy and/or bilateral oophorectomy

          -  BMI ≥ 40 kg/m2

          -  Inability to comprehend what will be done during the study or why it will be done.

          -  Being a study of older women with PCOS, children and men will be excluded.

          -  Pregnancy or lactation within the past 6 months. Subjects with a positive pregnancy
             test will be informed of the result by the screening physician.

          -  Prisoners.

          -  History of (or clinical evidence for) Cushing's syndrome or adrenal insufficiency.

          -  History of congenital adrenal hyperplasia or 17-hydroxyprogesterone (17-OHP) >200
             ng/dL, which suggest the possibility of congenital adrenal hyperplasia. 17-OHP will be
             collected during follicular phase. NOTE: if a 17-OHP >200 ng/dL and is confirmed on
             repeat testing, an ACTH-stimulated 17-OHP <1000 ng/dL will be required for study
             participation.

          -  Total testosterone >150 ng/dL, which suggests the possibility of virilizing neoplasm.

          -  DHEA-S greater than 1.5 times the upper limit of normal range (mild elevations may be
             seen in PCOS, so elevations < 1.5 times the upper limit of normal will be accepted in
             these groups).

          -  Virilization

          -  Diagnosis of diabetes mellitus (DM), fasting glucose ≥ 126 mg/dL, or a hemoglobin A1c
             of ≥ 6.5%.

          -  Abnormal thyroid stimulating hormone (TSH). Subjects with stable and
             adequately-treated hypothyroidism, reflected by normal TSH values, will not be
             excluded.

          -  Moderate to severe hyperprolactinemia. Mild prolactin elevations may be seen in PCOS,
             and elevations < 1.5 times the upper limit of normal will be accepted in this group.

          -  Persistent liver abnormalities, with the exception that mild bilirubin elevations will
             be accepted in the setting of known Gilbert's syndrome. Mild transaminase elevations
             may be seen in women with obesity, so elevations <1.5 times the upper limit of normal
             will be accepted in this group.

          -  Hemoglobin level is less than 11 g/dL.

          -  Persistent hematocrit <36% and hemoglobin <12 g/dL.

          -  Subjects who remain anemic after two sequential months of ferrous gluconate (325 mg
             twice daily) will be excluded from study participation.

          -  Abnormal sodium, potassium, or bicarbonate concentrations or elevated creatinine
             concentration.

          -  Significant history of pulmonary dysfunction (e.g., asthma or COPD requiring
             intermittent systemic corticosteroid, pulmonary hypertension, etc.).

          -  History of known or suspected congestive heart failure.

          -  History of known or suspected ischemic heart disease or cerebrovascular disease.

          -  History of moderate to severe hypertriglyceridemia (triglyceride level > 500 mg/dL).
             Subjects with stable and adequately treated hypertriglyceridemia reflected by normal
             triglyceride values will not be excluded.

          -  History of breast, ovarian, or endometrial cancer.

          -  The cut off threshold for estimated dominant ovarian cyst size on the day of r-hCG
             injection will be 18 mm. Since the ultrasound will be assessed 3-4 days prior to r-hCG
             administration, we will estimate the size of the dominant follicle (at the time of
             r-hCG administration) using the typical rate of ovarian follicle growth of 1.4 mm per
             day. If the dominant follicle size exceeds the cut off threshold, the subject will be
             asked to repeat the transvaginal ultrasound: if menses begin within 3 weeks of the
             prior ultrasound, the ultrasound would be repeated during the new menstrual cycle. If
             menses do not occur within 3 weeks of the prior ultrasound, the ultrasound will then
             be scheduled at the subject's earliest convenience.

          -  Ovarian enlargement, defined by ovarian volume greater than 15 mm on transvaginal
             ultrasound. If the ovarian volume exceeds the cut off threshold, the participant will
             be given an option to repeat the transvaginal ultrasound in 2-3 months.

          -  History of venous thromboembolism (e.g. deep venous thrombosis (DVT), pulmonary
             embolism (PE)).

          -  History of blood clotting disorders (e.g., protein C, protein S, positive
             antiphospholipid antibodies).

          -  First-degree relative history of blood clotting disorder, unless the same disorder has
             been formally excluded for the study subject. Note: any abnormal labs may be repeated
             to exclude a lab error.

          -  No medications known to affect the reproductive system can be taken in the 2 months
             prior to screening and 3 months prior to the study. Such medications include oral
             contraceptive pills, metformin, progestins, glucocorticoids, anti-psychotics and/or
             mood stabilizers that are known to cause hormone abnormalities.
Female
Accepts Healthy Volunteers
Subject must be at least 20 Years old.
Subject must be at most 49 Years

Patient description (medical language): A 32-year-old woman comes to the hospital with vaginal spotting.  Her last menstrual period was 10 weeks ago. She has regular menses lasting for 6 days and repeating every 29 days. Medical history is significant for appendectomy and several complicated UTIs. She has multiple male partners, and she is inconsistent with using barrier contraceptives. Vital signs are normal.  Serum β-hCG level is 1800 mIU/mL, and a repeat level after 2 days shows an abnormal rise to 2100 mIU/mL.  Pelvic ultrasound reveals a thin endometrium with no gestational sac in the uterus.

Patient description (patient's own words): I just turned 32 and last morning I woke up with strange blood stains on my underwear. My last periods were more than 2 months ago, which is unusual for me because I used to have regular periods lasting for 6 days every 29 days, more or less. I had several UTIs in the past. I also had appendicitis. I'm currently seeing several men and, to be honest, some of them do struggle to wear a condom. I went to the hospital to check myself up and they told me that my vitals were normal. I also had a blood test on Monday, and my β-hCG level was 1800 mIU/mL, and then on Wednesday, it went up to 2100 mIU/mL. The gynecologist also did an ultrasound and she told me that, hopefully, there was no ovule.

Does the patient match the trial criteria? Contradiction