Elsevier

Maturitas

Volume 38, Issue 2, 20 April 2001, Pages 157-163
Maturitas

Course of primary headaches during hormone replacement therapy

https://doi.org/10.1016/S0378-5122(00)00215-2Get rights and content

Abstract

Objective: The aim of the present study was to evaluate how hormone replacement therapy (HRT) could influence the course of primary headaches in postmenopausal women. Methods: Fifty patients presenting for clinical evaluation of menopausal status and suffering from headache were enrolled. The observational period lasted 7 months during which women filled in a diary with the clinical characteristics of headache attacks (frequency, days with headache, severity) and the analgesic use (no. of analgesic/month). Climacteric symptoms and both anxiety and depression were also measured. At the first visit the patients were divided into two groups: those suffering from migraine without aura (MwA) and those suffering from episodic tension-type headache (ETTH) and separately randomized. After a month of run-in period, they received two different HRT regimen, either: (1) transdermal estradiol 50 mcg every 7 days for 28 days plus medroxyprogesterone acetate (MAP) 10 mg/day from 15th to 28th day, or (2) oral conjugated estrogens 0.625 mg/day for 28 days plus MAP 10 mg/day for the last 14 days. Follow up evaluations were planned after 1, 3 and 6 months of treatment. Results: While we did not observe any significance change regarding headache parameters in ETTH patients during both transdermal and oral treatment, the course of migraine was significantly affected by the route of HRT. Both frequency of attacks (F=8.5; P<0.000) and days with headache (F=6.9; P<0.000) significantly increased during HRT in the subgroup assuming oral formulation. On the contrary, no changes in the same parameters were found in the group taking transdermal treatment. Moreover, while severity of migraine was unaffected by HRT, analgesic consumption was significantly increased in the subgroup on oral treatment (F=6.3; P=0.001). Conclusions: HRT significantly affects the course of headache in postmenopausal migraine sufferers. Indeed, while the clinical pattern of ETTH remained stable throughout the observational period, patients suffering from MwA worsened their symptoms within the first 3 months of treatment. In particular, the oral route of administration significantly worsened migraine in comparison to the transdermal route.

Introduction

Headache is a common gynecological problem during the reproductive life span. Indeed, migraine is ‘a female disease’ since its predominance is in women from puberty to menopause [1]. Moreover, both neuroendocrine events linked to reproductive stages and hormonal interventions, such as oral contraception and replacement therapy, may induce marked changes in the course of the disease [2], [3].

Several authors have long-time investigated the link between hormones and headache from both pathophysiological and clinic-epidemiological standpoints suggesting a role for hormonal fluctuations in precipitating headache attacks during the perimenstrual period [2], [3], [4], [5], [6], [7].

Migraine prevalence generally decreases with advancing age in both sexes and the lack of menstrual periodicity probably contributes to the improvement of the disease in postmenopausal women [8], [9]. However, under some circumstances erratic estrogen secretion and unbalanced estrogen exposure due to anovulatory cycles and/or progesterone deficiency may contribute to worsen migraine in the perimenopausal period [1]. Indeed, several population-based epidemiological studies reported a peak of migraine prevalence in women around 40–50 yr and a sharp decrease thereafter [10], [11], [12].

We previously showed that the postmenopausal course of headache with a premenopausal onset differed according to the type of headache and the type of menopause [13] in women not assuming hormonal replacement therapy (HRT). While migraine improved in almost two-thirds of cases, tension-type headache worsened or was unchanged in 70% of cases. On the other hand, women who had a physiologic menopause experienced a more favorable course of migraine than women who had a surgical menopause with bilateral oophorectomy suggesting that the abrupt estrogen withdrawal, probably coupled with the emotional impact of hysterectomy, is a well-defined aggravating factor of migraine. In addition, the intensity of climacteric symptomatology may contribute to trigger or aggravate headaches [14].

That notwithstanding, it is likely that HRT may significantly affect the natural history of headache at menopause, particularly when a regular bleeding is restored. However, only few retrospective, descriptive reports [15], [16], [17], [18], [19] are available on the use of HRT in headache sufferers at the time of menopause.

The aim of the present study was to evaluate how some types of HRT could influence the course of primary headaches in postmenopausal women in a randomized, prospective design.

Section snippets

Materials and methods

This randomized, prospective study was carried out from January 1997 to March 1999 at the Departments of Obstetrics and Gynecology of the Universities of Modena and Pavia. Out of 123 consecutive patients presenting for clinical evaluation of menopausal status and suffering from headache, 50 subjects were enrolled. Inclusion criteria were: spontaneous menopausal status of at least 6 months with FSH levels >30 mUI/l, primary headache (migraine without aura (MwA) or episodic tension-type headache

Results

Two MwA patients dropped out stopping HRT after 1 month (1 case) or never starting treatment (1 case). Three ETTH patients dropped out because of changing residence (1 case) or never starting treatment (two cases). Therefore, the effects of HRT were calculated in 28 MwA patients (14 undergoing oral and 14 undergoing transdermal regimen) and in 17 ETTH patients (9 undergoing oral and 8 undergoing transdermal regimen).

Discussion

The present study suggests that HRT significantly affects the course of migraine, but not of ETTH, in postmenopausal women.

This observation fits with the common knowledge that MwA is more sensitive to hormones [1], [2], [3] in comparison with ETTH which is more affected likely by psychological distress and coping strategies [23]. Moreover, it is of paramount interest to observe different effects exerted by the different routes of administration of HRT on the course of migraine. In particular,

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