Clinical trial NCT05061472: A 6-month Observational Study on Combined Oral Contraceptives and Body Weight in Pre-Menopausal Women With Overweight or Obesity
Official title: The Influence of Combined Oral Contraceptives on Weight, Body Composition, Eating Behaviors, and Appetite in Pre-menopausal Women With Overweight or Obesity
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Contraceptive Usage
Overweight or Obesity
Body Weight Changes
Appetitive Behavior
Eating Behavior
Keywords: Combined Oral Contraceptive Pill
Body Weight
Body Composition
Eating Behaviors
Appetite
Pre-menopausal Women
Overweight
Obesity
Non-Hormonal Contraception
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2021-09-29
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will be performed in a cohort of up to 64 females of reproductive age, age 18-40 years, with overweight or class I-III obesity (BMI 25-45 kg/m2) who initiate the Sprintec COC pill or remain on a NHC

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Premenopausal Women With Overweight/Obesity Who Initiated a COC vs. Continued NHC Use, Enrolled and Remained in This Study, and Completed Outcome Measures
timeFrame: Baseline, Month 6
Secondary outcomes:
Other outcomes:
measure: Body Weight
timeFrame: 6 Months
measure: BMI
timeFrame: 6 Months
measure: Percent Body Fat
timeFrame: 6 Months
Locations:
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Denver
country: United States
facility: Comprehensive Women's Health Center
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Adnin Zaman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Colorado, Denver
name: Victoria A Catenacci, MD
role: STUDY_CHAIR
affiliation: University of Colorado, Denver
name: Elizabeth A Thomas, MD
role: STUDY_CHAIR
affiliation: University of Colorado, Denver
name: Aaron Lazorwitz, MD
role: STUDY_CHAIR
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