New Consensus on Hormonal Management in Women With Stroke

Megan Brooks

January 20, 2017

A new multidisciplinary consensus document looks at the lifelong management of hormonal issues in women with previous stroke.

The document provides guidance on pregnancy management, contraception, and hormone replacement strategies among women with a stroke history.

"This multidisciplinary expert consensus provides evidence-based recommendations on the lifelong management of hormonal issues in women with previous stroke," Monica Acciarresi, MD, from the Stroke Unit at Santa Maria della Misericordia Hospital, University of Perugia, Italy, told Medscape Medical News.

This research, she explained, was prompted by a "clinical need to neurologists, strokologists, gynecologists, and endocrinologists in the management of women with previous stroke."

The American Heart Association Stroke Guidelines for Women published in 2014 cover risk factors unique to women, including reproductive factors, and factors that are more common in women, including migraine with aura, obesity, metabolic syndrome, and atrial fibrillation.

"However, the lifelong management of hormonal issues in women who have had stroke was not fully addressed regarding future pregnancies, type of delivery, labor induction, and secondary prevention during future pregnancy and lactation," Dr Acciarresi said.

"Furthermore, no indications were provided on the use of hormonal contraceptives, ovarian stimulation, hormone replacement therapies or other alternatives in women with previous stroke," she noted. Therefore, a multidisciplinary expert panel came together to search the literature and come up with a consensus document that covered those issues, she said.

The consensus document was published online January 9 in Stroke.

The panel's recommendations were rated, based on Grades of Recommendation Assessment, Development and Evaluation (GRADE), as 1 (strong: when benefit clearly outweighed risk and could be accepted with a high degree of confidence) or 2 (weak: when the benefits and risks were more closely matched and were more dependent on specific clinical scenarios) and divided into 3 categories: A (high quality), B (moderate quality), and C (low quality).

The panel concluded that for women with a history of stroke, future pregnancies are not contraindicated on the basis of available data (Grade 2, Level B).

For stroke prevention treatment during pregnancy, the authors' recommendations are based on two scenarios: a high-risk condition that would have called for anticoagulation or a lower-risk condition that would have called for antiplatelet therapy outside pregnancy.

They recommend that pregnant women with a defined low-risk condition may be considered for treatment with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) throughout the first trimester, followed by low-dose aspirin for the remainder of the pregnancy (Grade 2, Level B). According to the evidence, no recommendations on other types of antiplatelets other than aspirin can be given for pregnant women with low-risk conditions (Grade 2, Level C), they say.

In pregnant women with defined high-risk conditions, vitamin K antagonists should be avoided between the sixth and 12th weeks of gestation and close to term to avoid the delivery of an anticoagulated fetus. LMWH or UFH should be used (1) during these periods alone and alternated with vitamin K antagonists that have the same target international normalized ratio (INR) based on previous prescription or (2) during the entire pregnancy (Grade 2, Level B).

Pregnant women with a high-risk condition on novel oral anticoagulant (NOAC) treatment should be prescribed LMWH or UFH between the sixth and 12th weeks of gestation, while warfarin can be administered in the other periods. The vitamin K antagonist target INR needs to be based on the underlying pathology. Alternatively, UFH or LMWH may be prescribed throughout pregnancy (Grade 2, Level C).

Among the other key recommendations from the panel are the following:

  • Vaginal deliveries may be preferred to cesarean deliver. Cesarean delivery should be performed on the basis of obstetric indications and not on history of stroke (Grade 2, Level C).

  • When labor is pharmacologically induced, aspirin therapy may be continued (Grade 2, Level C).

  • Therapeutic doses of UFH/LMWH should be discontinued 24 hours before inducing labor and restarted within 24 hours if no contraindications exist (Grade 2, Level C).

  • Vitamin K antagonists may be restarted 24 hours after delivery without a loading dose (Grade 2, Level C).

  • During breast-feeding, use of low-dose aspirin, vitamin K antagonist, or UFH/LMH may be recommended. NOACs should be avoided during breast-feeding and, when necessary, substituted with LMWH/UFH or a vitamin K antagonist. No recommendations on antiplatelets besides aspirin during breast-feeding can be given (all Grade 2, Level C).

  • In women with previous stroke, no recommendation on ovarian stimulation can be given (Grade 2, Level C).

  • Oral contraceptives should not be recommended to women with prior stroke (Grade 1, Level B).

  • Hormone replacement therapy should not be recommended for hot flashes (Grade 1, Level A), but gabapentin may be recommended (Grade 2, Level C). No recommendation on use of selective serotonin reuptake inhibitors for hot flashes could be given (Grade 2, Level C).

"No recommendations on phytoestrogens can be provided due to a lack of data on their benefits. Finally, in menopause a healthy lifestyle without smoking habit, physical activity and an ideal BMI [body mass index] above normal should be targets," Dr Acciarresi told Medscape Medical News.

"Most of these recommendations," she noted, "are of limited strength and are based upon observational data, and it is unlikely randomized controlled trials will provide data on these issues in the near future."

Panel member Cheryl Bushnell, MD, MHS, professor of neurology and director of the Wake Forest Baptist Stroke Center in Winston-Salem, North Carolina, agrees. "There will never be randomized controlled trials to answer most of the questions that remain for how to best treat young women with a history of stroke who want to get pregnant in the future," she told Medscape Medical News.

"Therefore, a thorough search of the literature and recommendations from a multidisciplinary panel of experts is likely to be the next-best alternative and is still an excellent resource for clinicians. We also recommend development of registries of young women with a history of stroke during or around pregnancy in order to understand the lifetime risk after stroke in these young women," Dr Bushnell said.

"The research community would benefit from pooling their data on pregnant women and stroke victims in order to realize a clearer picture on global trends concerning secondary prevention and risk profiles," Dr Acciarresi added. "Data of this nature would provide the much-needed insight into the treatment safety and efficacy regarding antiplatelet selection and dosage and could aid in better defining predictive factors. An additional priority of future research should be to investigate on the role of ovarian stimulation on the vascular state, as this therapy is widely sought out by women due to falling fertility rates worldwide."

This research had no commercial funding. Dr Bushnell has received research funding without salary from the World Federation of Neurology for the International Maternal Newborn Stroke Registry. One author received speaker fees from both BI and Pfizer and is a member of BI Advisory Board. The other authors have disclosed no relevant financial relationships.

Stroke. Published online January 9, 2017. Abstract

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