A 6-month Observational Study on Combined Oral Contraceptives and Body Weight in Pre-Menopausal Women With Overweight or Obesity

Study Overview
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Brief Summary
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Approximately 15 million women of reproductive age women in the United States have overweight or obesity and use the combined estrogen and progestin oral contraceptive pill (COC). Although many women report weight gain as a side effect of COCs, a conclusive link between COC use and weight gain has not been established. This investigation will address a major gap in the literature by prospectively evaluating the influence of initiating a COC versus non-hormonal contraceptives (NHCs) on weight, body composition, eating behaviors, and appetite in pre-menopausal women with overweight or obesity. Aim 1 will assess the feasibility of recruiting and retaining a racially/ethnically diverse group of women with overweight and obesity while Aim 2 will explore changes in body weight, body composition, and cardiometabolic risks in these women; Aim 3 will explore changes in dietary and macronutrient energy intake, eating behaviors, and appetite in this subset of women. This research will help the investigators understand the extent to which COCs are associated with weight gain and help guide medical providers in counseling women with overweight and obesity on appropriate contraceptive methods.

Detailed Description
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The overall objective of this feasibility pilot study is to prospectively evaluate the effects of initiating a combined estrogen and progestin oral contraceptive (COC) compared to a non-hormonal contraceptive (NHC) on body weight, body composition, eating behaviors, and appetite in pre-menopausal women with overweight or obesity. Nearly half of the 61 million U.S. women of reproductive age have overweight or obesity, placing them and their offspring at an elevated lifetime risk of adverse cardiometabolic and health outcomes. Notably,  15-20% of reproductive-aged women use COCs. Though many women anecdotally report weight gain as a side effect of COCs, a conclusive link between COC use and weight gain has not been established. Previous studies evaluating COCs and weight change have excluded women with obesity, who may be at greater risk for contraceptive-associated weight gain. Given the widespread use of COCs, it is critical to understand the extent to which these contraceptive methods may be associated with weight gain and correlated cardiometabolic health risks in reproductive age women with established overweight or obesity. The reproductive hormonal profile of COC users differs substantially from that of normally cycling women. A recent study of seven typical COCs found that while median exposure to synthetic estrogens across a 28-day cycle was similar to median endogenous estrogen exposure, median synthetic progestin exposure was 4-fold higher than median endogenous progesterone exposure. COCs also lead to daily spikes in serum estrogen and progestin levels, unlike the gradual increase and cyclic patterns of endogenous hormones that characterize a normal menstrual cycle. COCs may impact weight via changes in appetite and satiety due to supraphysiologic systemic levels of reproductive hormones. For example, progesterone has been shown to increase appetite and trigger binge- or emotional-eating. The principal investigator has reported that use of COCs was associated with greater weight regain over 1 year after weight loss in women with overweight and obesity enrolled in a behavioral weight loss program. However, no studies have prospectively evaluated changes in body weight, cardiometabolic risk factors, and eating behaviors in women with overweight or obesity initiating COC vs. those using NHCs. This study's overall hypothesis is that initiation of COCs in women with overweight or obesity will be associated with greater weight gain and increases in cardiometabolic health risks than use of NHCs over 6 months. The investigators will recruit pre-menopausal women with overweight or obesity who have already elected to initiate COCs as well as a control group of age and BMI matched NHC users. The investigators will evaluate the feasibility of recruiting women initiating a COC and women using NHCs into a prospective, observational study as well as the feasibility of evaluating changes in weight, body composition, eating behaviors, and appetite over 6 months from COC initiation. The investigators propose the following specific aims: Aim 1: Assess the feasibility of recruiting and retaining a racially/ethnically diverse group of pre-menopausal women with overweight or obesity initiating COCs compared to age- and BMI-matched NHC users. The investigators aim to recruit  10 women per month for 6 months (N=24; n=12 COCs, n=12 NHCs; >20% in each group of African American or Hispanic race/ethnicity) and assess feasibility of completion of outcome measures. The investigators hypothesize that at least 80% of participants will continue their chosen contraceptive method and complete outcome measures within a 2-week window at 6 months. Exploratory Aim 2: Explore the influence of COC vs. NHC use on body weight, body composition, and cardiometabolic risk factors. The investigators hypothesize that women with overweight or obesity initiating COCs will exhibit greater increases in body weight, fat mass, homeostatic model assessment for insulin resistance (HOMA-IR), triglycerides, and blood pressure compared to age- and BMI-matched NHC users. Exploratory Aim 3: Explore the influence of COC vs. NHC use on energy intake (EI), eating behaviors, and appetite. The investigators hypothesize that women with overweight or obesity initiating COCs will have greater increases in dietary energy and fat/carbohydrate intake, hunger, disinhibition, reward-based eating, emotional eating, binge eating, and food cravings at 6 months compared to age- and BMI-matched NHC users.

Official Title
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The Influence of Combined Oral Contraceptives on Weight, Body Composition, Eating Behaviors, and Appetite in Pre-menopausal Women With Overweight or Obesity

Conditions
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Contraceptive Usage, Overweight or Obesity, Body Weight Changes, Appetitive Behavior, Eating Behavior

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females Age 18-40 years Overweight or class I-III obesity (BMI 25-45 kg/m2) Free of major psychiatric illnesses Electing to start the Sprintec (norgestimate/ethinyl estradiol 0.25mg/35mcg) COC Using non-hormonal forms of contraception: copper intrauterine device (Paragard), male condoms, tubal ligation, partner vasectomy, withdrawal/natural family planning, spermicide, abstinence, or other NHCs as determined by the investigators Exclusion Criteria: Diabetes Use of medications thought to affect body weight, energy intake, glycemic parameters, or estrogen (i.e. systemic glucocorticoids, stimulants, weight loss pharmacotherapy, metformin) History of weight loss surgery History of polycystic ovarian syndrome History of congenital adrenal hyperplasia Use of a different COC or hormonal contraception method within the past 3 months Planning pregnancy Planning to stop contraceptive within the next 6 months Planning to change diet or join a weight loss program or research study within the next 6 months Recent therapeutic abortion or miscarriage in the past 1 month if fetal gestational age <10 weeks, or 3 months if fetal gestational age >10 weeks Pregnancy with delivery in the past 6 months Currently lactating People with pregnancy potential who were assigned female at birth and either currently using or planning to use gender-affirming hormone therapy in the next 6 months Use of other forms of reproductive hormones such as testosterone or dehydroepiandrosterone (DHEA) Current tobacco use

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| COC<br>Pre-menopausal women with overweight or obesity who are newly initiating the combined oral contraceptive pill, Sprintec (norgestimate/ethinyl estradiol 0.25mg/35mcg) | |
| NHC<br>Pre-menopausal women with overweight or obesity who are using non-hormonal methods of birth control | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of pre-menopausal women with overweight or obesity who will initiate a COC vs. continue NHCs, enroll and remain in this study, and complete outcome measures | The investigators aim to recruit  10 women per month for 6 months (N=24; n=12 COCs, n=12 NHCs; >20% in each group of African American or Hispanic race/ethnicity) and assess feasibility of completion of outcome measures. The investigators hypothesize that at least 80% of participants will continue their chosen contraceptive method and complete outcome measures within a 2-week window at 6 months. | Baseline, month 3, month 6 (end of study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Body Composition, Eating Behaviors, Pre-menopausal Women, Overweight, Obesity, Non-Hormonal Contraception, Combined Oral Contraceptive Pill, Body Weight, Appetite