Hormone Replacement for Premature Ovarian Insufficiency

Premature ovarian insufficiency (POI) is a term used to describe when a woman's ovaries stop
working normally before the natural age of menopause. Early sequelae of POI include vasomotor
symptoms, vaginal dryness, mood swings and insomnia due to estrogen deficiency. Long-term
sequelae such as loss of bone mineral density and cardiovascular risk carry are considerable
concerns. While exogenous estrogen replacement is recommended for the POI patient population,
the optimal regimen for replacement is not clear. One approach to hormone replacement therapy
(HRT) is to mimic physiologic ovarian function through full replacement doses of estrogen
(either orally or transdermally) to reach the typical serum estradiol levels of a
menstruating woman (approximately 104 pg/mL per day) with cyclic progestin therapy for
endometrial protection. Another approach uses daily combined estrogen-progestin oral
contraceptives (COCs), for ease of administration and increased social acceptability. To
date, few studies have been performed comparing the two treatment methods in terms of quality
of life measures (vasomotor symptoms, bleeding profile, sexual dysfunction, satisfaction with
contraception), endocrine function, bone turnover or cardiovascular risk in POI patients. In
this proposal, the investigators intend to establish feasibility and acceptability of a pilot
randomized controlled trial comparing traditional HRT with COCs in women with POI and to
evaluate differences in quality of life measures, hormone assays, bone turnover and
cardiovascular risk between treatment arms. The investigators hypothesize that acceptability
and feasibility of the pilot trial will be high and that differences will be detected for all
measured variables between treatment arms. Demonstration of feasibility and acceptability of
this pilot would allow for the pursuit of a larger trial and identification of a superior
treatment regimen would have a meaningful impact on the short and long-term care of this
patient population.

Inclusion Criteria:

- Female patients,

- Between 14-45 years of age

- Post-menarchal

- Presence of uterus

- POI as defined by: change in menstrual function (oligomenorrhea and/or amenorrhea),
elevated serum serum follicle stimulating hormone (FSH), low serum estradiol
concentrations, or estrogen deficiency symptoms.

Exclusion Criteria:

- Pregnancy or lactation within previous 3 months

- Use of hormonal contraception or replacement within previous 3 months

- Any contraindication to oral contraceptive pills or hormone replacement therapy per
the current drug labels. These could include, but are not limited to: history of
venous thromboembolism,estrogen-sensitive cancer history, regular cigarette smoking
and history of or active liver disease, etc.

- Patients will be screened for pregnancy with a urine HCG test at time of screening