Investigation of Female Reproductive Hormone Dynamics During Adolescence

Irregular menstrual cycles are common in girls for several years after their first menstrual period. The cause of abnormal menstrual cycles during this time is not well-understood. The purpose of this study is to: 1) monitor girls during a menstrual cycle (with blood and urine sampling and serial pelvic ultrasounds) to identify those girls who do not ovulate (release of an egg from the ovary), and 2) determine whether cycles can be corrected by treating girls with a short course of low-dose estrogen and progesterone.

Study Overview

• Status: Completed
• Conditions: Menstruation Disturbances
• Intervention / Treatment: Drug: micronized progesterone; Drug: transdermal estradiol

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Reproductive Endocrine Unit, Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 16 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• no more than 3 ½ years postmenarchal

Exclusion Criteria:

• Subjects currently on or previously treated with medications that may affect reproductive hormones (eg birth control pills).
• Subjects with severe acne or hirsutism
• Subjects who exercise excessively (running > 20 miles/week or its equivalent)
• Subjects with any of the following medical conditions: diabetes, hypertension, hyperlipidemia, valvular heart disease, lupus, rheumatoid arthritis, migraine headaches with aura, undiagnosed breast mass, inflammatory bowel disease, gallbladder disease, sickle cell disease, or thrombophilia.
• Current smoker
• History of deep venous thrombosis or pulmonary embolism in subject or first-degree relative

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Interventional; estradiol 50 mcg transdermal patch x 7 days oral micronized progesterone 0.5 mg/kg/dose TID x 7 days	Drug: micronized progesterone; Drug: transdermal estradiol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ovulation in Cycle 2	serum progesterone > 3 ng/ml or presence of corpus luteum on pelvic ultrasound	20-40 days

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Janet Hall, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Ortega MT, Carlson L, McGrath JA, Kangarloo T, Adams JM, Sluss PM, Lambert-Messerlian G, Shaw ND. AMH is Higher Across the Menstrual Cycle in Early Postmenarchal Girls than in Ovulatory Women. J Clin Endocrinol Metab. 2020 Apr 1;105(4):e1762-71. doi: 10.1210/clinem/dgaa059.
• Sun BZ, Kangarloo T, Adams JM, Sluss P, Chandler DW, Zava DT, McGrath JA, Umbach DM, Shaw ND. The Relationship Between Progesterone, Sleep, and LH and FSH Secretory Dynamics in Early Postmenarchal Girls. J Clin Endocrinol Metab. 2019 Jun 1;104(6):2184-2194. doi: 10.1210/jc.2018-02400.
• Sun BZ, Kangarloo T, Adams JM, Sluss PM, Welt CK, Chandler DW, Zava DT, McGrath JA, Umbach DM, Hall JE, Shaw ND. Healthy Post-Menarchal Adolescent Girls Demonstrate Multi-Level Reproductive Axis Immaturity. J Clin Endocrinol Metab. 2019 Feb 1;104(2):613-623. doi: 10.1210/jc.2018-00595.

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: June 24, 2015
• First Submitted That Met QC Criteria: June 30, 2015
• First Posted (Estimate): July 1, 2015

Study Record Updates

• Last Update Posted (Actual): December 24, 2018
• Last Update Submitted That Met QC Criteria: June 18, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Menstruation Disturbances; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Progestins; Estradiol; Progesterone
• Other Study ID Numbers: 2013P-000513

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No