Clinical trial NCT01389141: Age-related Changes in Ovarian Follicular Wave Dynamics
Official title: Ovarian Follicular Wave Dynamics During The Menstrual Cycle: Relationship To Age, Reproductive Hormones And Musculoskeletal Health
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Aging
Keywords: ovary
follicle
hormones
bone
muscle
Lead sponsor: University of Saskatchewan
Sponsor class: OTHER
Collaborators: name: Canadian Foundation for Women's Health
First posted: 2011-07-07
Enrollment: 70
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Seventy healthy women, exhibiting all inclusion criteria and no exclusion criteria will be enrolled in this study. Women will be grouped into 1 of the following age categories:

1. . Mid-reproductive age (MRA): 18-35 years
2. . Late reproductive age-1 (LRA1): 36-44 years
3. . Late reproductive age -2 (LRA2): 45-55 years (this group will include women in the LRA, EMT and LMT groups, as previously characterized by STRAW)

Brief summary: The investigators hypothesize that age-related changes in the number and growth dynamics of ovarian follicles will be associated with changes in hormone levels and corresponding changes in musculoskeletal health.

Detailed description: The following hypotheses will be tested:

1. Differences in ovarian follicular wave dynamics will be detected in women of different ages;
2. The numbers and patterns of ovarian follicle waves in women are repeatable over multiple menstrual cycles;
3. Differences in inhibin B, inhibin A, and AMH will be detected in women with 2 versus 3 or more follicular waves
4. Differences in FSH, LH, progesterone, inhibin B, inhibin A, and AMH detected in MRA and LRA2 women, will change with the numbers of follicles and waves detected;
5. 'Luteal out of phase events' (aka LOOP cycles) will be more prevalent in LRA2 versus MRA women, and will represent major anovulatory waves and/or ovulatory waves;
6. When compared to MRA group, LRA2 women will have lower bone mineral mass and areal density at the lumbar spine; reduced trabecular density at the distal radius and thinner cortices with lower cortical density at the radial and tibial shaft. Other bone outcomes will be similar between the groups;
7. When compared to MRA group, LRA2 women will have lower total body lean mass, greater fat mass and less dense muscle tissue at the forearm and lower limb and lower hand grip strength.
8. Reduced bone mineral mass, areal density, trabecular density, cortical density and hand grip strength in LRA2 versus MRA women will be associated with reduced follicle number, a greater prevalence of LOOP cycles, higher serum FSH and lower inhibin concentrations

Eligibility criteria: Inclusion Criteria:

* Informed consent obtained
* Age of 18-55
* 18\<BMI\<35
* Menstrual cycle history:
* MRA group: regular cycles
* LRA-1 group: history of regular cycles, with variable cycles allowed (no more than 3 months amenorrhea)
* LRA-2 group: variable cycles allowed (no more than 3 months amenorrhea)
* Has not taken hormonal contraception within 2 months of initiating study procedures
* Agrees to use back-up contraception throughout the course of the study, if sexually active (condoms to be provided)
* 3.0 \< Prolactin \< 20.0 ug/L
* 0.30 \< TSH \< 5.50 mIU/L
* Normal complete blood count (CBC)
* Beta human Chorionic Gonadotropin \< 5IU/L.

Exclusion Criteria:

* Smokers
* Documented ovarian failure
* History of or currently-diagnosed infertility of unexplained or female origin;
* Medical conditions known or suspected to interfere with reproductive function (including PCOS)
* Presence of only one ovary
* Ovaries inaccessible with transvaginal ultrasonography
* The use of any medications known or suspected to interfere with reproductive function
* Ongoing pregnancy
* Lactation
* Participation in an investigational drug trial in the 30 days prior to the pre-study visit
* Planning to undergo surgery during the course of the study.

Primary outcomes:
measure: Follicle diameter (mm)
timeFrame: 4 years
Secondary outcomes:
measure: - Follicle number
timeFrame: 4 years
measure: Serum FSH
timeFrame: 4 years
measure: bone mineral density
timeFrame: 4 years
measure: Serum LH
timeFrame: 4 years
measure: Serum Estradiol
timeFrame: 4 years
measure: Serum Progesterone
timeFrame: 4 years
measure: Serum Inhibin A
timeFrame: 4 years
measure: Serum Inhibin B
timeFrame: 4 years
measure: Serum AMH
timeFrame: 4 years
Other outcomes:
Locations:
city: Saskatoon
country: Canada
facility: Reproductive Biology Research Unit, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Saskatchewan
state: Saskatchewan
Study officials:
affiliation: University of Saskatchewan
name: Angela R Baerwald, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Baerwald AR, Adams GP, Pierson RA. Characterization of ovarian follicular wave dynamics in women. Biol Reprod. 2003 Sep;69(3):1023-31. doi: 10.1095/biolreprod.103.017772. Epub 2003 May 14.
citation: Baerwald AR, Adams GP, Pierson RA. A new model for ovarian follicular development during the human menstrual cycle. Fertil Steril. 2003 Jul;80(1):116-22. doi: 10.1016/s0015-0282(03)00544-2.
citation: Bashir ST, Baerwald AR, Gastal MO, Pierson RA, Gastal EL. Follicle growth and endocrine dynamics in women with spontaneous luteinized unruptured follicles versus ovulation. Hum Reprod. 2018 Jun 1;33(6):1130-1140. doi: 10.1093/humrep/dey082.
citation: Baerwald A, Vanden Brink H, Hunter C, Beuker D, Lim H, Lee CH, Chizen D. Age-related changes in luteal dynamics: preliminary associations with antral follicular dynamics and hormone production during the human menstrual cycle. Menopause. 2018 Apr;25(4):399-407. doi: 10.1097/GME.0000000000001021.
citation: Vanden Brink H, Robertson DM, Lim H, Lee C, Chizen D, Harris G, Hale G, Burger H, Baerwald A. Associations Between Antral Ovarian Follicle Dynamics and Hormone Production Throughout the Menstrual Cycle as Women Age. J Clin Endocrinol Metab. 2015 Dec;100(12):4553-62. doi: 10.1210/jc.2015-2643. Epub 2015 Oct 14.