Case Rep Womens Health. 2020 Apr 21;27:e00206. doi: 10.1016/j.crwh.2020.e00206. eCollection 2020 Jul.
Patients with surgical menopause often present to their primary care provider with menopausal symptoms. Here we present an unusual case of palmar arch artery occlusion in a 55-year-old woman with primary Raynaud’s disease taking oral combined menopausal hormone therapy after surgical menopause for endometriosis. She was successfully treated with intravenous infusion of prostaglandin E1 and nitroglycerin patches over two weeks. Menopausal hormone therapy was stopped and her vasomotor symptoms did not recur.
The most effective treatment for menopausal symptoms is MHT with systemic estrogen. MHT includes a wide range of hormonal products, doses and routes of administration. Estrogen as a single systemic agent is appropriate in women after hysterectomy, but estrogen plus concomitant progestogen is required in the presence of a uterus for endometrial protection . Combined MHT may be used after hysterectomy to prevent reactivation of pre-existing endometriosis. However, randomized clinical trials have shown that combined oral MHT containing estrogen plus progestin is associated with risk of breast cancer, arterial or venous disease and thromboembolic events [4,5].
Primary Raynaudˈs disease is characterized by constriction of the small arteries of the extremities in response to cold, pain, or emotional stimuli. Increased vasoconstriction is mediated by activation of the alpha-2 adrenoreceptors. In these patients the intracellular signalling pathway is modified and causes increased sensitivity of contractile proteins to calcium in the smooth muscle of cutaneous vessels. Intravascular abnormalities including platelet activation with increased thromboxane, defective fibrinolysis and reduced deformability of red blood cells can also be present . Few studies have been published on the use of MHT in women with Raynaudˈs disease but some factors as cigarette smoking or estrogen could be implicated in disease evolution . Animal studies have shown that estrogen upregulates alpha-adrenergic receptor, stimulates the release of norepinephrine and increases the sensitivity of small arteries to epinephrine and norepinephrine with a potential negative effect . In contrast, other studies have reported that progesterone either has little effect or has an effect opposite to that of estrogen .
Studies regarding MHT and Raynaud’s disease are limited. A cross-sectional study of women from the Framinghan Offspring Cohort examined 49 women diagnosed with Raynaudˈs phenomenon. In that small sample, unopposed estrogen therapy was associated with Raynaud phenomenon, but this association was not present in women receiving combined hormone therapy . In our patient, combined MHT was prescribed for protection against reactivation of the endometriosis. The combination of oral estradiol with norethisterone has been associated with a lower risk of thrombosis compared to conjugated equine estrogen with medroxyprogesterone, but higher thrombosis risk than estradiol with dydrogesterone or micronized progesterone or unopposed estradiol by transdermal route [11,12]. In this regard, it is important to remember that MHT formulation, dose and route of administration may have different effects on target organs and potentially allow options to minimize risk.
Lastly, menopause management should be holistic and include lifestyle recommendations regarding diet, exercise, smoking cessation and safe levels of alcohol consumption