A randomized trial of transdermal and oral estrogen therapy in adolescent girls with hypogonadism

Abstract

BackgroundAdolescent females with ovarian failure require estrogen therapy for induction of puberty and other important physiologic effects. Currently, health care providers have varying practices without evidence-based standards, thus investigating potential differences between oral and transdermal preparations is essential. The purpose of this study was to compare the differential effects of treatment with oral conjugated equine estrogen (OCEE), oral 17β estradiol (OBE), or transdermal 17β estradiol (TBE) on biochemical profiles and feminization in girls with ovarian failure.Study design20 prepubertal adolescent females with ovarian failure, ages 12–18 years, were randomized to OCEE (n = 8), OBE (n = 7), or TBE (n = 5) for 24 months. Estrogen replacement was initiated at a low dose (0.15 mg OCEE, 0.25 mg OBE, or 0.0125 mg TBE) and doubled every 6 months to a maximum dose of 0.625 mg/d OCEE, 1 mg/d OBE, or 0.05 mg/d TBE. At 18 months, micronized progesterone was added to induce menstrual cycles. Biochemical markers including sex hormones, inflammatory markers, liver enzymes, coagulation factors, and lipids were obtained at baseline and 6 month intervals. Differences in levels of treatment parameters between the groups were evaluated with one-way analysis of variance (ANOVA). The effect of progesterone on biochemical markers was evaluated with the paired t-test.ResultsMean (±SE) estradiol levels at maximum estrogen dose (18 months) were higher in the TBE group (53 ± 19 pg/mL) compared to OCEE (14 ± 5 pg/mL) and OBE (12 ± 5 pg/mL) (p ≤ 0.01). The TBE and OBE groups had more effective feminization (100% Tanner 3 breast stage at 18 months). There were no statistical differences in other biochemical markers between treatment groups at 18 months or after the introduction of progesterone.ConclusionsTreatment with transdermal 17β estradiol resulted in higher estradiol levels and more effective feminization compared to oral conjugated equine estrogen but did not result in an otherwise different biochemical profile in this limited number of heterogeneous patients. OBE and TBE provide safe and effective alternatives to OCEE to induce puberty in girls, but larger prospective randomized trials are required.Trial registrationClinical Trials Identifier: NCT01023178.

Estrogen-based hormone therapy in women with primary ovarian insufficiency: a systematic review

“…Four [17 21 23 24] of 12 studies were conducted in women with POI due to chemotherapy or bone marrow transplantation; six included women with idiopathic POI [14–16 19 20 22], and two included women with more than one etiology of POI (mixed populations) [18 25]. The most common formulations of hormone therapy were t-E2 and o-CEE combined with medroxyprogesterone acetate (MPA); duration of therapy ranged from 6 to 120 months.…”

“…A pre-post study of 9 female patients showed no significant changes in total cholesterol, LDL, HDL or triglycerides after 9 months [19]. No conclusions could be drawn from an RCT that included 2 participants of interest with POI secondary to chemotherapy BMT receiving o-CEE+MP, as authors reported changes based on HRT formulation and not by etiology of hypogonadism [24]. A two-year study which included a subset of patients with POI of eligible etiologies reported that between 10 women with POI treated with o-CEE plus a progestogen versus 5 women with POI who were untreated, there were no changes in serum lipid levels.…”

Evolving pituitary hormone deficits in primarily isolated GHD: a review and experts’ consensus

“…Subsequently, cyclic progestin should be added for 14 days. The pleaded advantages in comparison to oral treatment are minimization of the first path effect, higher IGF-1 serum levels [ 50 ], better feminization [ 51 ], and potentially a better cardiovascular risk profile in adulthood [ 52 , 53 ]. Major disadvantages are the lack of suitable estradiol patches, the lack of long-term trials comparing transdermal and oral treatment, the lack of knowledge with respect to adherence, and the absence of approval for the transdermal indication.…”

An adolescent girl with premature ovarian failure, Graves’ disease, and chronic urticaria: a case report

“…DiVasta and Gordon recommended administration of 1/8 th to 1/10th of the adult estrogen dose before the patient's height reaches the expected height in order to avoid any negative effects on the final adult height [16]. A randomized controlled trial by Shah et al showed that transdermal estrogen administration was more effective than oral administration [17]. The recommended starting dose is 0.0125 mg/day, which is doubled every 6 months to a maximum dose of 0.05 mg/day, and progesterone is added after 18 months of treatment.…”