VTE was diagnosed in 115 women using transdermal estradiol and 164 women using oral estrogen. Compared with the rate in women initiating oral estrogen, women using transdermal estradiol had a significantly lower incidence of VTE than oral estrogen users (adjusted incidence rate ratio, 0.67).
Is HT safe for women who have a history of VTE?
The US Food and Drug Administration has designated a personal history of VTE as a contraindication to all estrogen and estrogen-progestin HT formulations in the package labeling for these products. Because accumulating evidence is reassuring in regard to the risk of VTE with transdermal HT, however, it seems reasonable to consider using HT in selected women who have a history of VTE.
In a retrospective cohort study, French investigators assessed the impact of oral and transdermal estrogen on the risk of recurrent VTE in 1,023 postmenopausal women who had an earlier diagnosis of VTE. During follow-up, most of the subjects did not use HT, although 103 used transdermal estrogen and 10 used oral estrogen.
Seventy-seven women experienced recurrent VTE during a mean of 79 months after discontinuing anticoagulation. Compared with non-use of estrogen therapy, use of transdermal estrogen was not significantly associated with recurrent VTE (hazard ratio [HR], 1.0); oral estrogen, however, was associated with a substantial and significantly increased risk of recurrent VTE (HR, 6.4).
WHAT THIS EVIDENCE MEANS FOR PRACTICE
In the 2011 OBG Management Update on Menopause, I examined two large observational studies3,4—one from France, the other from Great Britain—that provided convincing evidence that transdermal HT does not, in contrast with oral HT, raise the risk of VTE. These new reports, from North America and France, provide further support for the hypothesis that transdermal HT is safer from the perspective of VTE risk. Although a randomized trial that compares the risk of VTE in women using oral estrogen with the risk in women using transdermal estrogen might put this matter to rest, I don’t anticipate that a trial to address this outcome, with adequate statistical power, will be performed any time soon.
In my practice, most of the estrogen that I prescribe for menopausal women is transdermal. Using transdermal estrogen may be particularly important in patients who are at increased risk of VTE at baseline, including obese women.
The small numbers of thrombotic events in the cohort of women who had a history of VTE limits confidence in the findings of this French report. Nevertheless, this study provides a small measure of reassurance regarding use of transdermal estrogen after VTE.
Only rarely have I prescribed HT to women who have a history of VTE. These exceptional patients have been highly symptomatic and extensively counseled about the risk of recurrent thrombosis as well as the off-label status of hormone use, given their medical history. Certainly, if you consider prescribing HT to such women, the transdermal route (preferably at a dosage of 0.05 mg, or lower) would be more prudent that oral HT.
Hysterectomy may accelerate the onset of menopause
Moorman PG, Myers ER, Schildkraut JM, Iversen ES, Wang F, Warren N. Effect of hysterectomy with ovarian preservation on ovarian function. Obstet Gynecol. 2011;118(6):1271–1279.
Novetsky AP, Boyd LR, Curtin JP. Trends in bilateral oophorectomy at the time of hysterectomy for benign disease. Obstet Gynecol. 2011;118(6):1280–1286.
Does hysterectomy hasten ovarian failure?
In a prospective cohort study from North Carolina, Moorman and colleagues followed 1) 406 women who did not have malignancy who underwent hysterectomy, with conservation of at least one ovary and 2) 465 women who had an intact uterus (overall age range, 30 to 47 years). Within 5 years of follow-up, ovarian failure had occurred in 60 women who had undergone a hysterectomy and in 46 women who had an intact uterus (adjusted HR, 1.9).
Ovarian failure occurred almost 2 years earlier in women who had undergone a hysterectomy than it did in those whose uterus was intact. The likelihood of ovarian failure was higher in the setting of unilateral oophorectomy than when both ovaries had been conserved.
Hysterectomy for benign disease: Are we performing fewer oophorectomies?
Investigators in New York State followed trends in concomitant bilateral oophorectomy among women undergoing hysterectomy for benign disease, from 2000 to 2006. Overall, the rate of concomitant oophorectomy declined by 8% during this period; among women younger than 55 years, the rate of oophorectomy declined by more than 10%. The rate of concomitant bilateral oophorectomy was higher among women who had a family history of breast or ovarian cancer and among those who had a personal history of breast cancer, ovarian cysts, or endometriosis.