title: Implications of diminished ovarian reserve (DOR) extend well beyond reproductive concerns.
abstract: OBJECTIVE
  To investigate whether a diagnosis of diminished ovarian reserve (DOR) in premenopausal years has adverse implications for skeletal health and quality of life.
  
  
  METHODS
  This was a cross-sectional study of infertile, albeit healthy, mid-reproductive-age women (younger than 42 y) attending an academic infertility practice.
  
  
  RESULTS
  Eighty-nine women with varying causes of infertility were prospectively enrolled. Serum (cycle d 1-3) was collected for markers of ovarian reserve, bone metabolism, testosterone, and free androgen index. Bone mineral density (BMD) was assessed and categorized as low if the Z score was less than -1.0). Infertile women with DOR (n = 28) demonstrated significantly higher serum follicle-stimulating hormone levels (P < 0.001), lower müllerian-inhibiting substance (MIS) levels (P < 0.001), smaller ovarian dimensions (P < 0.05), lower testosterone levels (P = 0.035), lower free androgen index (P = 0.019), and enhanced bone metabolism (P = 0.003); although the prevalence of low BMD was higher in women with DOR who were younger than 41, this relationship was not of statistical significance (P = 0.106). Women younger than 41 years of age with DOR were significantly more likely to manifest disturbed sleep (P = 0.049) and acknowledge dissatisfaction with sexual intimacy (P = 0.004) compared with those with infertility and normal ovarian reserve. After adjustment for potential confounders, a diagnosis of DOR was significantly associated with low BMD, increased bone turnover, sexual dissatisfaction, and disturbed sleep.
  
  
  CONCLUSIONS
  Our data suggest that DOR unmasked in the context of infertility evaluation has adverse implications for a woman's well-being that extend well beyond the thus far appreciated reproductive concerns. A decline in ovarian hormones, specifically estrogen and testosterone, concomitant with DOR may be hypothesized as a mechanism that can explain the observed multisystem ramifications of DOR including increased bone turnover, low BMD, sexual distress, and disturbed sleep.
authors.affiliation: Department of Obstetrics and Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA. lubnapal@hotmail.com
authors.forename: Lubna
authors.initials: L
authors.lastname: Pal
authors.forename: Kris
authors.initials: K
authors.lastname: Bevilacqua
authors.forename: Gohar
authors.initials: G
authors.lastname: Zeitlian
authors.forename: Jun
authors.initials: J
authors.lastname: Shu
authors.forename: Nanette
authors.initials: N
authors.lastname: Santoro
mesh_terms: D000328:Adult; D000375:Aging / Q000502:physiology; D054304:Anti-Mullerian Hormone / Q000097:blood; D001851:Bone Diseases, Metabolic / Q000150:complications*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007246:Infertility / Q000503:physiopathology*; D019964:Mood Disorders / Q000150:complications; D006080:Ovarian Follicle / Q000503:physiopathology*; D017697:Premenopause / Q000502:physiology*; D016649:Primary Ovarian Insufficiency / Q000097:blood / Q000150:complications*; D011446:Prospective Studies; D011788:Quality of Life; D012044:Regression Analysis; D012735:Sexual Dysfunction, Physiological / Q000150:complications; D007319:Sleep Initiation and Maintenance Disorders / Q000150:complications; D013739:Testosterone / Q000097:blood
chemical_list: D013739:Testosterone; D054304:Anti-Mullerian Hormone; D005640:Follicle Stimulating Hormone