12 June 2017
Cardiovascular disease is the leading cause of morbidity and mortality in postmenopausal women [1]. Hormone replacement therapy (HRT) has been shown to reduce future risk of cardiovascular disease when taken within 10 years of the menopause. Avoiding HRT in menopausal women can actually be detrimental to their health. Some experts are now recommending that HRT should be considered as part of a general prevention strategy for women at the onset of the menopause [2]. However, some doctors and nurses feel very apprehensive about this as they are confused about the association of HRT with cardiovascular disease (CVD).
The negative publicity regarding the misinterpretation in the media of the Women’s Health Initiative (WHI) study has led to many women and health-care professionals still being concerned and anxious about the potential risks of HRT [3], in particular regarding HRT and cardiovascular disease (CVD). A large proportion of doctors are still informing women that HRT is associated with a greater risk of CVD and are refusing to prescribe HRT for women who would actually benefit from taking it. Many women with hypertension are still being told to stop taking their HRT. This misperception is resulting in large numbers of women needlessly enduring menopause symptoms and also increasing their future risk of osteoporosis, cardiovascular disease and diabetes by not taking HRT.
Evidence to support HRT
The benefits and risks of HRT vary by dosage, regimen, and timing of initiation. Data accumulated from numerous studies have shown that, in women under the age of 60 years with symptoms or other indications, initiating HRT near their menopause provides a favorable benefit/risk ratio. This has been reiterated in the NICE and IMS guidance [4,5].
Symptoms of the menopause, such as hot flushes, mood swings, night sweats and reduced libido, all usually improve with HRT. There is now robust and compelling data suggesting that, apart from quality-of-life issues, prevention of coronary disease, reduction in osteoporosis and fracture risk, reduction in new-onset diabetes mellitus and all-cause mortality occur6. There are no other treatments currently available to our patients that are able to confer this prevention role.
Age and years since the menopause are now known to be important variables affecting the benefit/risk profile of HRT [7]. Starting HRT less than 10 years since a woman’s menopause has been shown to lead to a significant reduction in death and a reduction in CVD [4]. There is a lower incidence of CVD in those women who take HRT within 10 years of their menopause [3].
Progestogens have differing effects on cardiovascular risk. In general, those progestogens more similar to progesterone have been associated with a lower impact than the more androgenic progestogens [8]. Micronized progesterone seems to have a neutral or beneficial effect on blood pressure in postmenopausal women [9]. In contrast to other progestogens, progesterone has been shown to antagonize the effect of aldosterone, causing natriuresis and a reduction in blood pressure [10]. This is important as hypertension is a major risk factor for coronary heart disease and stroke.
Recommendations
Although NICE is fairly conservative in its recommendations, they state [4] that women should be informed that:
- HRT with estrogen alone is associated with no, or reduced, risk of coronary heart disease;
- HRT with estrogen and progestogen is associated with little or no increase in the risk of coronary heart disease;
- Taking HRT under 60 years does not increase a woman’s risk of CVD;
- The presence of cardiovascular risk factors is not a contra-indication to HRT;
- It is essential to optimally manage any underlying cardiovascular risk factors (e.g. blood pressure, cholesterol).
The IMS guidelines [5] state that the initiation of estrogen-only HRT reduces coronary heart disease and all-cause mortality. They also state that the daily continuous oral estrogen-progestogen data are less robust but other combined therapy regimens appear to be cardioprotective.
Premature ovarian insufficiency and CVD
Early menopause is associated with increased risk of cardiovascular disease events and mortality [11]. Women who have a bilateral sapingo-oophrectomy at a young age appear to have an even greater risk than those women who have an early natural menopause. Women with premature ovarian insufficiency (POI) have a higher risk of premature atherosclerosis and unfavorable lipid profiles.
HRT for women with POI has beneficial effects on plasma lipids, insulin resistance and also on endothelial function. HRT and the combined contraceptive pill containing ethinylestradiol would both be suitable options for hormone replacement, although HRT may be more beneficial in improving cardiovascular markers compared to the combined oral contraceptive pill [12]. In addition, HRT may have a beneficial effect on blood pressure when compared with a combined oral contraceptive, so is preferable in women with raised blood pressure [13]. It is therefore essential that women with POI receive appropriate hormones to replace premenopausal levels of ovarian sex steroids to increase their quality of life and also to ameliorate the associated health risks with this condition [11].
All women with POI should receive hormone therapy at least until the age of the natural menopause (51 years) unless there are contraindications [4,11]. In addition to improving symptoms, hormone therapy has repeatedly been shown to be beneficial in maintaining their long-term health and reducing the future risk of osteoporosis and cardiovascular disease [14].
Summary
The menopausal period and early menopause are an ideal opportunity to assess cardiovascular risk and women should often be considered for HRT at an earlier stage in order to gain maximum cardiovascular protection from taking HRT. Women with POI and women within 10 years of their menopause can potentially gain significant improvements in their cardiovascular health, as well as their general health, by being offered HRT. It is of utmost importance that health-care professionals are educated properly regarding the potential health benefits to be gained by taking HRT.
I totally agree with the notion of considering HRT to as many women as possible as a treatment to reduce future cardiovascular disease.
Louise Newson
References
- Collins P, Webb CM, de Villiers TJ, Stevenson JC, Panay N, Baber RJ. Cardiovascular risk assessment in women – an update. Climacteric 2016;19:329–36
http://www.ncbi.nlm.nih.gov/pubmed/27327421 - Lobo RA, Pickar JH, Stevenson JC, Mack WJ, Hodis HN. Back to the future: hormone replacement therapy as part of a prevention strategy for women at the onset of menopause. Atherosclerosis 2016;254:282-90
http://www.ncbi.nlm.nih.gov/pubmed/27745704 - Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002; 288: 321-33
http://www.ncbi.nlm.nih.gov/pubmed/12117397 - Menopause: diagnosis and management. NICE 2015.
https://www.nice.org.uk/guidance/ng23 - Baber RJ, Panay N, Fenton A; the IMS Writing Group. 2016 IMS Recommendations on women’s midlife health and menopause hormone therapy. Climacteric 2016;19:109-50
http://www.ncbi.nlm.nih.gov/pubmed/26872610 - Boardman HM, Hartley L, Eisinga A, et al. Hormone therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database Syst Rev 2015 Mar 10;3:CD002229
http://www.ncbi.nlm.nih.gov/pubmed/25754617 - Sood R, Faubion SS, Kuhle CL, et al. Prescribing menopausal hormone therapy: an evidence-based approach. Int J Womens Health 2014;6:47-57
http://www.ncbi.nlm.nih.gov/pubmed/24474847 - Stanczyk FZ, Hapgood JP, Winer S, Mishell DR. Progestogens used in postmenopausal hormone therapy: differences in their pharmacological properties, intracellular actions, and clinical effects. Endocr Rev 2013;34:171–208
http://www.ncbi.nlm.nih.gov/pubmed/23238854 - Honisett SY, Pang B, Stojanovska L, Sudhir K, Komesaroff PA. Progesterone does not influence vascular function in postmenopausal women. J Hypertens 2003;21:1145–9
http://www.ncbi.nlm.nih.gov/pubmed/12777951 - Boschitsch E, Mayerhofer S, Magometschnigg D. Hypertension in women: the role of progesterone and aldosterone. Climacteric 2010;13:307–13
http://www.ncbi.nlm.nih.gov/pubmed/20443718 - POI Guideline Development Group. Management of women with premature ovarian insufficiency. 2015.
https://www.eshre.eu/Guidelines-and-Legal/Guidelines/Management-of-premature-ovarian-insufficiency.aspx - Faubion SS, Kuhle CL, Shuster LT, Rocca WA. Long-term health consequences of premature or early menopause and considerations for management. Climacteric 2015;18:483–91
http://www.ncbi.nlm.nih.gov/pubmed/25845383 - Sullivan SD, Sarrel PM, Nelson LM. Hormone replacement therapy in young women with primary ovarian insufficiency and early menopause. Fertil Steril 2016;106:1588-99
http://www.ncbi.nlm.nih.gov/pubmed/27912889 - Hamoda H; British Menopause Society and Women’s Health Concern. The British Menopause Society and Women's Health Concern recommendations on the management of women with premature ovarian insufficiency. Post Reprod Health 2017;23:22-35
http://www.ncbi.nlm.nih.gov/pubmed/28381102