Search:
Menopause Live - IMS Updates
InFocus

Date of release: 23 July, 2018

Hysterectomy as a new cardiovascular and metabolic risk factor

Hysterectomy with or without oophorectomy is a common procedure all over the world, mostly for benign conditions [1,2]. Notwithstanding, the long-term safety of hysterectomy alone has not been accurately evaluated. Studies addressing this issue have methodological flaws: not controlling for pre-existing cardiovascular disease, inclusion of unilateral oophorectomy in the ovarian conservation group, and short-term follow-up [3,4].



Laughlin-Tommaso and colleagues have studied a cohort of 2094 women in Olmsted County in the USA; the women underwent hysterectomy with ovarian conservation (both ovaries) for benign conditions between the years 1980 and 2002, and were matched with women who had not undergone this procedure [5]. Indications for hysterectomy were mainly leiomyomas (39.5%), uterine prolapse (20.3%), and menstrual disorders not specifically defined (25.5%). They evaluated the incidence of de novo cardiovascular disease and associated metabolic conditions, by using electronic registry of the outcome for a median follow up of 21.9 years. The study found a significant correlation between the development of cardiometabolic disease and hysterectomy, in all age groups.

Comment

In earlier decades, hysterectomy for benign causes was usually performed with bilateral oophorectomy, arguing protection against ovarian cancer. Nowadays, ovarian preservation in the case of a hysterectomy is more frequent, especially in younger women [6], considering the deleterious effects of hypoestrogenism on the cardiovascular system, bone, mood, and health in general.

This study intended to evaluate the long-term safety of hysterectomy alone related to cardiovascular aspects. Though the design was observational, the methodology and adjustments for potential confounders were carefully addressed. The authors matched cases by age, by 20 different chronic conditions, and by educational level and race.

It is interesting to note that the increased risk of cardiometabolic disease described in this paper shows a pattern very similar to that observed in the menopausal transition (SWAN study). Overall, the curves displayed for the evolution of the appearance of cardiovascular risk factors and disease separate approximately 10 years after hysterectomy. But in women younger than 35 years, the risks of adverse cardiovascular outcomes (including coronary artery disease, congestive heart failure and cardiac arrhythmias) begin to increase after 20 years of hysterectomy (50–55 years of age), i.e. just the time at which menopause is expected to occur.

The main strengths of the study are: (1) all women lived in Olmsted County at the time of hysterectomy, and were recruited before the procedure to assess de novo outcomes; (2) 97% of women in Olmsted County gave a general authorization research, minimizing volunteer and selection bias; (3) individual outcomes were confirmed twice with an ICD-9 code to avoid error in coding and recall bias in a patient; and (4) the long term follow-up (median 21.9 years) gives this study a high potency (low type beta error).

On the other hand, limitations are minimal: ICD-9 code error could occur, but this was minimized by checking two times. Also, women in the hysterectomy group could have had more medical visits and more reporting of the outcome (surveillance bias). Finally, they did not have information on, and did not pair, for potential confounders: smoking and physical activity.

Other epidemiological studies have shown that hysterectomy is associated with an elevation of FSH to more than 40 IU/l 4 years before in comparison to women without hysterectomy [7]. This FSH elevation is due to decreased inhibin B production by the ovary. Why hysterectomy produces ovarian dysfunction is not clear. Two potential mechanisms arise: one anatomical and one functional. The former could be the decreased collateral ovarian blood flow. The latter could be uterine factors that act in an endocrine or paracrine manner, maintaining ovarian function.

Comentario

Stefano Macchiavello


Resident Endocrinology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile



Paulina Villaseca


Endocrinology Department, Pontificia Universidad Católica de Chile



    References

  1. Jacobson GF, Shaber RE, Armstrong MA, Hung YY. Hysterectomy rates for benign indications. Obstet Gynecol 2006;107:1278-83


    http://www.ncbi.nlm.nih.gov/pubmed/16738152

  2. Wu JM, Wechter ME, Geller EJ, Nguyen TV, Visco AG. Hysterectomy rates in the United States, 2003. Obstet Gynecol 2007;110:1091-5


    http://www.ncbi.nlm.nih.gov/pubmed/17978124

  3. Falkeborn M, Schairer C, Naessen T, Persson I. Risk of myocardial infarction after oophorectomy and hysterectomy. J Clin Epidemiol 2000;53:832-7


    http://www.ncbi.nlm.nih.gov/pubmed/10942866

  4. Ingelsson E, Lundholm C, Johansson AL, Altman D. Hysterectomy and risk of cardiovascular disease: a population-based cohort study. Eur Heart J 2011;32:745-50


    http://www.ncbi.nlm.nih.gov/pubmed/21186237

  5. Laughlin-Tommaso SK, Khan Z, Weaver AL, Smith CY, Rocca WA, Stewart EA. Cardiovascular and metabolic morbidity after hysterectomy with ovarian conservation: a cohort study. Menopause 2018;25:483-92


    http://www.ncbi.nlm.nih.gov/pubmed/29286988

  6. Perera HK, Ananth CV, Richards CA, et al. Variation in ovarian conservation in women undergoing hysterectomy for benign indications. Obstet Gynecol 2013;121:717-26


    http://www.ncbi.nlm.nih.gov/pubmed/23635670

  7. Farquhar CM, Sadler L, Harvey SA, Stewart AW. The association of hysterectomy and menopause: a prospective cohort study. BJOG 2005;112:956-62


    http://www.ncbi.nlm.nih.gov/pubmed/15957999