Age-related Changes in Ovarian Follicular Wave Dynamics

Ovarian Follicular Wave Dynamics During The Menstrual Cycle: Relationship To Age, Reproductive Hormones And Musculoskeletal Health

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.

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

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.