Estrogen Sensitivity and Ovulatory Dysfunction in Obesity
Condition: Obesity; Infertility
MeSH terms: Infertility; Obesity
Study type: Interventional

Summary: 
      The sole purpose of this study is to evaluate pathophysiology of disease. The disease state
      that is being evaluated is the obesity-related alterations in reproductive hormones

        -  The obesity epidemic in the United States is advancing at an accelerated pace. It is
           estimated that by 2015, 41% of U.S. adults will be obese as defined by a body mass index
           (BMI) of greater than 30 kg/m2. The U.S. government's 2010 Dietary Guidelines regard
           obesity as the single greatest health hazard in this century. Female adult obesity is
           associated with menstrual cycle irregularities, ovulatory dysfunction and a higher risk
           of obstetrical complications. This reproductive phenotype of obesity is worsened by
           further increases in BMI and is not solely due to anovulatory infertility. While the
           association of adiposity with subfertility is well documented in population studies, the
           underlying mechanisms remain poorly understood. The main objective of this proposal is
           to clarify the nature of the obesity-related reproductive endocrine abnormalities and
           identify potential etiologies amenable to therapy.

        -  Hypothesis: The hypothalamic-pituitary axis is abnormally sensitive to estradiol
           negative feedback in obesity.
    

Detailed description: 
      -  Design: paired assessments Pre and Post estrogen administration in obese and normal
           weight women

        -  AIM 1: To test the pituitary and hypothalamic responsiveness in obesity, we will examine
           the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) pulsatility during
           frequent blood sampling.

        -  AIM 2: To test the ovarian responsiveness in obesity, we will examine urinary
           reproductive hormones (E1c, estrone conjugates, and Pdg, pregnanediol glucuronide) over
           an entire menstrual cycle.

        -  AIM 3: To test the hypothesis that central adiposity is associated with reproductive
           hormone alterations in obesity, we will quantitatively assess body composition by dual
           energy x-ray absorptiometry (DXA).
    

Intervention name(s): Estradiol; Gonadotropin-releasing hormone (GnRH); Progesterone
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Subjects were instructed to apply 0.1 mg/d transdermal estrogen for one month.; Pituitary response was assessed to determine how estradiol administration alters pituitary sensitivity to GnRH.; Subjects who failed to initiate a menstrual period following 40 days on the patch were instructed to take 200 mg daily of progesterone for 10 days or as long as deemed necessary.
Other intervention name(s): Climara, transdermal estrogen; Lutrelef or gonadorelin acetate; Prometrium or medroxyproge sterone acetate
Intervention MeSH terms: Hormones; Estradiol; Progesterone; Estrogens
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: LH pulsatility; Obesity; Reproduction