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Hormone Therapy in Women with Premature Ovarian Failure: Is Transdermal Safer Than Oral?

Results of a small Scottish trial suggest that the answer is yes.

Conventional treatment for premature ovarian failure consists of oral contraceptives (OCs) or menopausal hormone therapy. In an open-label, randomized, crossover trial, investigators in Scotland compared the effects of an OC (30 µg of ethinyl estradiol and 1.5 mg of norethindrone daily for 21 days, followed by 7 hormone-free days) with those of transdermal estrogen (0.1-mg estradiol patch, week 1; 0.15-mg patch, weeks 2 and 3; no estrogen, week 4) plus cyclical vaginal or oral progesterone. Participants received one treatment for 12 months and then switched to the alternative treatment (after washout) for 12 months. Blood pressure and renal factors (e.g., plasma angiotensin II levels) were measured at baseline and at 3, 6, and 12 months of each treatment period. Participants (age range, 19–38) had ovarian failure that was idiopathic or associated with cancer therapy, surgery, or Turner syndrome; none were hypertensive at baseline.

Eighteen women completed the trial. Compared with OC therapy, transdermal estrogen therapy was significantly associated with lower systolic and diastolic BPs at all time points. At 12 months, 24-hour mean systolic and diastolic BPs were lower by 7.3 and 7.4 mm Hg, respectively, with transdermal estrogen than with OCs (P<0.01 for both). In addition, transdermal estrogen therapy was associated with significantly lower plasma angiotensin II levels.

Comment: Few researchers have assessed the safety of different HT regimens in young women who lack ovarian function, so this trial is welcome. Clinicians should be aware that the highest-dose estradiol patch that is available in the U.S. releases 0.1 mg of estradiol daily. Furthermore, these investigators used cyclic therapy, which can result in withdrawal bleeding; I find that many of my patients prefer continuous HT. The authors speculate that higher BP associated with OC use reflects greater hepatic exposure to estrogen, leading to excessive angiotensinogen production and subsequent activation of the renin–angiotensin system. In women who experience natural menopause at normal ages, risk for venous thromboembolism is lower with transdermal than with oral estrogen therapy (JW Womens Health Apr 5 2007). The results of this small trial suggest that transdermal estrogen therapy might also have safety benefits over OC therapy for ovarian failure in women who are younger than 50.

— Andrew M. Kaunitz, MD

Published in Journal Watch Women's Health May 21, 2009

Citation(s):

Langrish JP et al. Cardiovascular effects of physiological and standard sex steroid replacement regimens in premature ovarian failure. Hypertension 2009 May; 53:805.

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Reader Remarks:

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• CRP in oral vs transdermal HT
  Zeev Blumenfeld, Technion,Israel, 26 May 2009 1:44 PM EST
  High C-reactive protein levels are associated with oral hormonal menopausal therapy but not with intrauterine levonorgestrel and transdermal estradiol.CRP is... [more]
• Transdermal safer than oral
  Ron P D'Agostino D.O., L'Anse, MI, 26 May 2009 1:44 PM EST
  Imagine how much better the results would have have been with a properly prescribed bioidentical hormone replacement; 1) real progesterone(P4),calendar... [more]
• Hormone Therapy in Women with Premature Ovarian Failure: Is Transdermal Safer Than Oral?
  CA Granger, The Granger Partnership, 15 Jun 2009 7:53 AM EST
  This trial is too brief and too small to enable meaningful conclusions of safety to be drawn. Long term side... [more]