Thus, the proposed study has the following Specific Aims and Hypotheses:
1. To determine in menstruating women ages 18-45 whether an OCP containing ethinyl
estradiol (EE) and the progestin ethinydiol diacetate (ED) increases cortical GABA
concentrations as measured using proton magnetic resonance spectroscopy (1H-MRS) above
that of an OCP containing EE and the progestin norethindrone (NOR).
2. To determine the relationship between changes in occipital GABA concentrations with
acute OCP administration and negative affect with chronic OCP administration over two
Approximately 11.6 million women in the United States use oral contraceptives (OCs) each
year. The vast majority of OCs combine both estrogen and a type of progestin, or
progesterone-like substance into one pill which is taken daily. Depression or a negative
change in mood, apparently resulting from the use of OCs, is thought to be one of the main
reasons women miss pills or stop taking their oral contraceptive pills (OCPs) altogether.
Clinical observation that some women develop depression when taking progestin only OCs or
when adding progestins to menopausal estrogen therapy has led to the speculation that the
progestin is the likely culprit of these negative mood changes in women using combined OCPs.
The current study is designed to investigate the role of progestins in the development of
mood symptoms in OCP users. Women participating in this study will receive one of two
different OCPs for three months. Their mood while taking the OCPs will be compared to their
mood prior to using OCPs. In addition, each woman will undergo a brain imaging study after
the first dose of their OCP to determine whether acute changes in brain chemistry in
response to the OCP predicts change in mood with OCP use. By choosing OCPs with the same
estrogen product but 2 different types of progestins we hope to determine whether one type
of progestin is more likely to result in negative mood.
Determining factors that contribute to the emergence of depression with OC use is the first
step in developing newer oral contraceptives that do not have this health outcome and will
ultimately improve compliance with OCP use. Reducing side effects of OCPs is likely to
improve compliance and thus decrease the prevalence of unwanted pregnancy.
- Aged 18 - 42 years old and able to give voluntary written informed consent.
- Willing to complete a daily log of mood symptoms for 3 consecutive menstrual cycles.
- Be off of OCPs for at least 3 menstrual periods prior to beginning the study and be
willing to go on OCPs for the study.
- Provide documentation of a normal PAP smear, pelvic and breast examination within the
previous 12 months prior to enrollment.
- Have regular menstrual cycles 28 to 32 days in length prior to enrollment. The
screening cycle must be ovulatory as confirmed by plasma progesterone levels of >3
ng/ml during the luteal phase.
- Negative pregnancy blood test at admission; negative urine pregnancy test on the MRS
- Presence of any DSM-IV Axis I disorder, excepting possible mild to moderate PMS/PMDD,
within the previous 12 months.
- Lifetime history of any psychotic disorder, including bipolar disorder.
- Meeting DSM-IV criteria for psychoactive substance (including nicotine)
abuse/dependence within the preceding 6 months.
- A history of serious medical or neurological illness, including (but not limited to)
major cardiovascular disease, hypertension (SBP > 140 mm Hg and DBP > 90 mm Hg),
intracranial mass lesions, seizure disorder, severe hepatic or renal disease,
unstable endocrine or metabolic disease, unstable hematologic disease, gynecologic
cancer and gallbladder disease, venous thromboembolism, and stroke.
- Diabetes if present with one other cardiovascular risk factor such as
hypercholesterolemia or hypertension.
- Hypercholesterolemia if LDL > 160 mg/dl.
- Use of any psychotropic medication within the previous month.
- Alcohol consumption greater than 7 drinks/week.
- Current pregnancy or planning to become pregnant during the course of the study.
- Metallic implants.
- History of or suspected claustrophobias.
- Migraine headaches if > 35 yo.
- Weigh >300 lbs (the 4T magnet has a weight limit <300 lbs)