Estrogen and Triglycerides
Scientific Update, July 17, 2003. Jewish Hospital Cholesterol Center
AN OBSERVATIONAL STUDY OF SEVERE HYPERTRIGLYCERIDEMIA, HYPERTRIGLYCERIDEMIC ACUTE PANCREATITIS, AND FAILURE OF TRIGLYCERIDE- LOWERING THERAPY WHEN
ESTROGENS ARE GIVEN TO WOMEN WITH AND WITHOUT FAMILIAL HYPERTRIGLYCERIDEMIA .
Naila M. Goldenberg MD. Ping Wang PhD, Charles J. Glueck MD.
From the Cholesterol Center, Jewish and Alliance Hospitals.
Clin Chim Acta 2003;332:11-9
Capsule summary:
- Never give exogenous estrogens, evista, tamoxifen, or clomid without first measuring fasting plasma triglycerides. Exogenous estrogens are
contraindicated in women with pre-existing triglycerides = 500 mg/dl.
- In women with triglycerides = 300 mg/dl who fail to normalize triglycerides with diet, diabetes control, alcohol restriction, and either Lopid or
Tricor, who are also taking exogenous estrogens or evista, the estrogens and evista must be stopped in order to control the triglyceride levels.
- In women who develop hypertriglyceridemic pancreatitis while taking exogenous estrogens, evista, tamoxifen, or clomid, these agents must be stopped,
so that low fat diet, diabetes control, absolute alcohol restriction, and either Lopid or Tricor can lower the high triglycerides which have caused the
pancreatitis.
Abstract
Background. In an observational study, we assessed severe hypertriglyceridemia, hypertriglyceridemic acute pancreatitis, and failure of
triglyceride-lowering therapy when estrogens were given to 56 women with and without familial hypertriglyceridemia. The 56 women had been consecutively
referred to our center over a 3 year period because of triglycerides > 400 mg/dl despite diet-drug treatment and/or a history of hypertriglyceridemic
acute pancreatitis (AP). Of the 56 women, 17 had received estrogen replacement therapy (ERT), hormone replacement (HRT, n=6), or selective estrogen
receptor modulators (SERM, n=1).
Methods: After study at entry, in 56 women (median age 52 years), 36 with familial hypertriglyceridemia, to lower triglycerides, estrogens and
SERMs (hormone treatment, HT) were stopped; a very low fat diet (<15% of calories), Gemfibrozil (1.2 to 1.5 mg/day), and omega-3-fatty acid (4 to 12
g/day) were started, with restudy 2-4 weeks later.
Results: Of the 56 women, 24 (43%) were taking HT at entry, with median fasting triglycerides 1270 mg/dl in the HT group and 1087 mg/dl in the
no-HT group. Seventeen women (30%) had a history of AP, 9 of whom
(53%) were/had been on HT at the development of AP. Significant positive correlates of triglycerides at entry in a stepwise regression model were
hemoglobin A1C (partial R2=10.7%, p = .034) and an interaction between estrogen use and familial hypertriglyceridemia (partial R2=15%, p= .017). After 2-4
weeks on therapy, median triglycerides in the previous-HT group fell from 1270 mg/dl to 284 mg/dl (p< .0001) and in the no-HT group from 1087 to 326
mg/dl (p< .0001).
Conclusions: Before starting HT, to avoid HT induced hypertriglyceridemic AP and exacerbation of overt or covert familial hypertriglyceridemia,
triglycerides must be measured. HT is contraindicated in women with preexisting hypertriglyceridemia (triglycerides ³
500 mg/dl). Triglyceride-lowering diets and drugs often fail in the presence of HT and/or poorly controlled diabetes mellitus, but commonly succeed when
HT is stopped and diabetes mellitus is tightly controlled.
Introduction
High triglyceride levels are a significant independent predictor of coronary heart disease [1-4] and ischemic stroke [5]. Hypertriglyceridemia is often
associated with low high-density lipoprotein cholesterol that contributes to cardiovascular disease and stroke [6]. Hypertriglyceridemia may be associated
with rheological and impaired fibrinolytic mechanisms that can contribute to the development of atherothrombosis [7-10]. Recently, the National
Cholesterol Education Program (ATP III) identified optimum triglycerides as < 150 mg/dl, borderline 150-199 mg/dl, and high as 200-499 mg/dl [11].
Triglyceride levels ³ 500 mg/dl were classified as very high [11].
Marked hypertriglyceridemia (usually >2000 mg/dl) commonly causes acute pancreatitis [12-23]. Many patients with triglycerides > 1000 mg/dl have
familial hypertriglyceridemia with superimposed additional exogenous factors which further raise triglyceride levels: exogenous estrogens, SERMs
(raloxifene, nolvadex), clomiphene, physiologic hyperestrogenemia of pregnancy [22,24], poorly controlled diabetes mellitus (DM) [15], hypothyroidism,
alcohol excess [25], exogenous corticosteroids, and drugs including isotretinoin and protease inhibitors. Non-diabetic, non-alcoholic patients with
drug-induced hypertriglyceridemia account for 15 to 20 percent of cases with triglycerides > 2000 mg/dl [13]. Severe drug-induced triglyceride levels
>1000 md/dl are more likely to occur in patients with underlying familial hypertriglyceridemia [12,13,16].
Exogenous estrogens increase production of triglyceride-carrying very low density lipoproteins by the liver and reduce the levels of lipoprotein lipase
and hepatic lipase, thus reducing triglyceride clearance [15,16,26,27]. Exogenous estrogen may also elevate triglycerides by augmentation of insulin
resistance [28]. Estrogen-containing oral contraceptives can produce a 40% reduction of insulin sensitivity associated with increased plasma free fatty
acids, cholesterol, and triglyceride levels [29].
In an observational study, we assessed severe hypertriglyceridemia, hypertriglyceridemic acute pancreatitis, and failure of triglyceride lowering
therapy when estrogens were given to 56 women with and without familial hypertriglyceridemia. The 56 women had been consecutively referred to our center
over a 3 year period because of triglycerides > 400 mg/dl despite diet-drug treatment and/or a history of hypertriglyceridemic acute pancreatitis (AP).
Of the 56 women, 17 had received estrogen replacement therapy (ERT), hormone replacement (HRT, n=6), or selective estrogen receptor modulators (SERM,
n=1).
References:
E-mail: glueckch@healthall.com
or cglueck@fuse.net
Fax: 513-585-7950
