Effects of Estrogen Replacement on Bone Geometry and Microarchitecture in Adolescent and Young Adult Oligoamenorrheic Athletes: A Randomized Trial

Abstract

Oligoamenorrheic athletes (OAs) have lower bone mineral density (BMD) and greater impairment of bone microarchitecture, and therefore higher fracture rates compared to eumenorrheic athletes. Although improvements in areal BMD (aBMD; measured by dual-energy X-ray absorptiometry) in OAs have been demonstrated with transdermal estrogen treatment, effects of such treatment on bone microarchitecture are unknown. Here we explore effects of transdermal versus oral estrogen versus no estrogen on bone microarchitecture in OA. Seventy-five OAs (ages 14 to 25 years) were randomized to (i) a 100-μg 17β-estradiol transdermal patch (PATCH) administered continuously with 200 mg cyclic oral micronized progesterone; (ii) a combined 30 μg ethinyl estradiol and 0.15 mg desogestrel pill (PILL); or (iii) no estrogen/progesterone (NONE) and were followed for 12 months. Calcium (≥1200 mg) and vitamin D (800 IU) supplements were provided to all. Bone microarchitecture was assessed using high-resolution peripheral quantitative CT at the distal tibia and radius at baseline and 1 year. At baseline, randomization groups did not differ by age, body mass index, percent body fat, duration of amenorrhea, vitamin D levels, BMD, or bone microarchitecture measurements. After 1 year of treatment, at the distal tibia there were significantly greater increases in total and trabecular volumetric BMD (vBMD), cortical area and thickness, and trabecular number in the PATCH versus PILL groups. Trabecular area decreased significantly in the PATCH group versus the PILL and NONE groups. Less robust differences between groups were seen at the distal radius, where percent change in cortical area and thickness was significantly greater in the PATCH versus PILL and NONE groups, and changes in cortical vBMD were significantly greater in the PATCH versus PILL groups. In conclusion, in young OAs, bone structural parameters show greater improvement after 1 year of treatment with transdermal 17β-estradiol versus ethinyl estradiol-containing pills, particularly at the tibia.

Tibial Macrostructure and Microarchitecture Adaptations in Women During 44 Weeks of Arduous Military Training

“…( 58 ) Young oligomenorrheic athletes who received transdermal estradiol increased trabecular number over 12 months of training to a greater extent than those who received a COCP, providing some support for the role of estradiol in trabecular microarchitecture adaptations to mechanical loading in young women; however, there were no differences between the estradiol patch and no treatment. ( 59 ) Although low estradiol is a plausible mechanism to explain differences in trabecular adaptation, P1NP, and sclerostin between groups, there was no difference in estradiol between contraceptive groups (Gifford et al, unpublished data). We did not, however, standardize measurements around the menstrual cycle or contraceptive use, or measure ethinyl estradiol.…”

Characterizing the resting metabolic rate ratio in ovulatory exercising women over 12 months

“…2 Under conditions of negative energy balance, the physiological process of growth and reproduction are directly affected, as evidenced by the suppressed metabolism and the consequential decrement in metabolic hormones such as the thyroid hormones, insulin-like growth factor-1, and insulin. 4 In exercising women, persistent energy deficiency can lead to the development of menstrual disturbances, 5 where the independent 6 and combined effects of energy and estrogen deficiency result in detrimental impacts to bone strength and quality, [7][8][9] known as the Female Athlete Triad (Triad). 10,11 Additional factors which may contribute the development of energy deficiency and downstream physiological consequences include participation in leanness or aesthetic sports, [12][13][14] disordered eating behaviors (ie, increased drive for thinness 15,16 and increased dietary cognitive restraint 17,18 ), and clinical eating disorders.…”

Bone Perspectives in Functional Hypothalamic Amenorrhoea: An Update and Future Avenues

“…Crucially, there were no significant differences in weight or menstrual function change between the patch and pill groups by the end of the study, that could have confounded these results. Microarchitectural indices also improved significantly in the patch versus COCP group, especially at the tibia ( 107 ). These aforementioned findings in oligo-amenorrhoeic athletes are mirrored in females with AN.…”