Conditions: Obesity
Keywords: LH pulsatility Obesity Reproduction
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 62
Healthy volunteers: yes

Brief summary:
The purpose of this study is to determine why obese women have lower hormone levels and less fertility than women of normal body weight. The proposal will examine the reproductive system at the level of the brain and the ovary to define the changes that happen leading to lowered hormone production. Women will be studied throughout a menstrual cycle and given medications that will test how well their pituitary gland can make hormones that stimulate the ovary (luteinizing hormone (LH) and follicle stimulating hormone (FSH)). They will also be given a medication to abolish estrogen production in the body and their response to this medication will be assessed. Finally, the ovary's ability to produce progesterone after ovulation will be examined.

--Hypotheses:

1. Obese women have reduced pituitary sensitivity to exogenous gonadotropin-releasing hormone (GnRH), but normal clearance of exogenous LH. (comparative study of obese compared to normal weight women)
2. Obese women have abnormally increased sensitivity to estradiol negative feedback which will be reversed by an aromatase inhibitor. (comparative study of obese compared to normal weight women)

Detailed description:
AIM 1: test the hypothesis that reduced pituitary sensitivity to GnRH-induced LH and FSH secretion causes the relative hypogonadotropic hypogonadism of obesity AIM 2: test the hypothesis that the hypothalamic-pituitary axis is abnormally sensitive to estradiol negative feedback in obesity

Arms:
arm 1: Group 2:

* BMI ≥30 kg/m2
* History of regular menstrual cycles every 25-40 days

Gonadorelin-GnRH (Lutrepulse), GnRH antagonists - Cetrorelix (Cetrotide), Recombinant LH (Luveris) were administered in Aim 1. GnRH or gonadorelin (Lutrepulse) and Letrozole were administered in Aim 2. arm 2: * BMI 18-25 kg/m2
* History of regular menstrual cycles every 25-35 days

Gonadorelin-GnRH (Lutrepulse), GnRH antagonists - Cetrorelix (Cetrotide), Recombinant LH (Luveris) were administered in Aim 1. GnRH or gonadorelin (Lutrepulse) and Letrozole were administered in Aim 2.

Interventions: intervention 1: Cetrorelix intervention 2: Gonadorelin-GnRH intervention 3: Recombinant LH intervention 4: Letrozole
Intervention descriptions: intervention 1: Abolishes pituitary sensitivity to GnRH. intervention 2: GnRH is used to stimulate the pituitary gland to produce LH and FSH. intervention 3: Used to stimulate ovarian function in women. intervention 4: An aromatase inhibitor.

Protocol document: