INTRODUCTION
Hysterectomy is the most common non-obstetric surgery performed on women. Previous data show hysterectomy is performed in the United States in as many as 600,000 procedures annually, and 30% of women aged 60 years have undergone hysterectomy surgery [1]. In Indonesia, previous data at Cipto Mangunkusumo Hospital showed that the prevalence of hysterectomy procedures reached 18% annually. The uterus (and sometimes both of the ovaries) is removed during hysterectomy. Therefore, it also has the effect of accelerating the effect of menopause for a woman.
Hysterectomy has an impact on the production of prostaglandins in the uterine arteries and prostanoid receptors on myometrial myocytes cells, causing several changes to the vascular system [2].
In addition to having a vasodilating effect, the ovaries also have a cardioprotective effect. The cardioprotective effect of the ovary comes from the hormone estrogen, which is mediated through both genomic and non-
genomic mechanisms that include increased synthesis and release of vasodilator substances such as nitric oxide (NO). Estrogen also plays a role in maintaining a balanced blood lipid profile by increasing High-Density Lipoprotein (HDL) and triglycerides while lowering Low- Density Lipoprotein (LDL) [2].
Hypertension is the most significant risk factor for cardiovascular disease. According to the Center for Disease Control and Prevention (CDC), 1 of 3 people in America has hypertension [3]. Similar to these data, hypertension in Indonesian women aged 15–44 years is 27.8% [4]. Hysterectomy was associated with an increased risk of developing hypertension leading to a 40% increased risk of other vascular diseases in patients under 50 years old (HR, 2.22; 95% CI, 1.01-4.83) [5].
Previous studies have stated that the incidence of hypertension is estimated only to appear 4–5 years after hysterectomy [6].
Hysterectomy is a procedure that is often performed on gynecological disorders, especially in women of reproductive age. Hysterectomy can increase the risk
Blood Pressure Elevation Timing Following Hysterectomy
Kartiwa Hadi Nuryanto
*, Kanadi Sumapraja, Marcel Elian Suwito, Eka Rusdianto Gunardi, Seno Adjie, Tofan Widya Utami
Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
A R T I C L E I N F O
Received : 28 December 2021 Reviewed : 19 January 2022 Accepted : 22 March 2022 Keywords:
diastolic, hypertension, hysterectomy, mean arterial pressure, systolic
A B S T R A C T
Background: Hysterectomy is the most common non-obstetric surgery in adult, reproductive-age women. Hysterectomy with or without ovarian conservation is known to increase the risk of cardiovascular disease. However, only a few studies regarding its immediate and short-term effects on hypertension are available. This study aimed to determine changes in blood pressure after a hysterectomy procedure.
Methods: This study is a prospective cohort study of patients who underwent a total hysterectomy procedure with or without ovarian conservation at Cipto Mangunkusumo Hospital, Indonesia, from July 2018 to July 2020. Samples were grouped into patients with total hysterectomy only or hysterectomy with ovarian conservation (HT/HTSOU) and bilateral salpingo-oophorectomy hysterectomy (HTSOB). Statistical analysis was done using paired t-test and Wilcoxon test.
Results: There were 80 patients included in this study (40 for each group). A significant increase in all blood pressure components occurred at 12 months after the HT/HTSOU and HTSOB procedures (p < 0.05). After six months of the HTSOB procedure, the increase in blood pressure components only occurred in systolic blood pressure and mean arterial pressure (MAP) (p < 0.05).
Conclusions: There was a significant increase in all blood pressure components in the HT/HTSOU and HTSOB group at 12 months following hysterectomy while there was a significant increase in systolic blood pressure and MAP in the HTSOB group at 6 months following hysterectomy.
*Corresponding author:
Kartiwa Hadi Nuryanto Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
of hypertension. However, there has been no in-depth research on the effects and the timing of the effects.
Therefore, it is necessary to study a population of women who have undergone a hysterectomy procedure in Indonesia to determine its impact on the incidence of hypertension. This study aimed to determine changes in blood pressure after a hysterectomy procedure.
METHODS
A prospective cohort study was done on all reproductive-age women undergoing hysterectomy at Cipto Mangunkusumo Hospital, Indonesia, from July 2018 to July 2020. The subjects were followed up individually from the procedure until 1 year after the procedure. The blood pressure was only measured on the 6th and 12th months.
This study used a 5% error bound and 95%
confidence interval limit, with the power of the test considered to be 90%. The inclusion criteria for this research were all women aged under 45 years and having undergone hysterectomy with or without ovarian conservation. Subjects with prior hypertension, abnormal lipid profile, elevated glucose level, obesity, pregnancy, consuming anti-hypertensive drugs, or smoking were excluded from the study. Subjects who died during the follow-up period or did not come for follow-up examinations were dropped out.
The sampling was done using a consecutive sampling method. Subjects were grouped into two study groups, namely patients with total hysterectomy only or hysterectomy with ovarian conservation (HT/HTSOU) and patients with bilateral salpingo-oophorectomy
hysterectomy (HTSOB). All patients were followed up for at least a year following the procedure.
Blood pressure examination was done at the study center by blinded nurses or medical health workers working in the study location according to the recommendation of the Indonesian Hypertension Association (InaSH) about the correct steps of blood pressure examination. The sphygmomanometers used in this study were Riester® mercury sphygmomanometers which were routinely calibrated. Blood pressure examination was done twice per visit and averaged [7].
The blood pressure measurements were done monthly during the follow-up period. The blood pressure elevation was defined by an increase of a minimum of 1 point in either systolic or diastolic blood pressure.
Clinical data taken from the subjects were age in years, parity (grouped into primiparity and multiparity), heart rate, preoperative weight, indication, and body mass index. Collected data were then analyzed using SPSS for Macintosh ver. 20. Characteristics of subjects and examination results were analyzed descriptively.
Data with normal distribution were presented in mean
± standard deviation while data with abnormal distribution were presented in median (range). Statistical analysis was done using paired t-test and Wilcoxon test.
RESULT
Throughout the study, 80 subjects were included (40 for each group). Baseline characteristics of subjects can be found in Table 1. Based on the analysis, it was found that the characteristics of subjects between groups were relatively similar.
Characteristics HT/HTSOU
n (%) HTSOB
n (%)
Age (years), average + SD 36.55 + 5.7 37.95 + 5.4
20–40 25 (62.5%) 23 (57.5%)
40–45 15 (37.5%) 17 (42.5%)
Parity
Primiparity 8 (20%) 13 (32.5%)
Multiparity 32 (80%) 27 (67.5%)
Heart rate (beats per minute), median (range) 83 (63-114) 86 (65-115) Preoperative weight (kg), median (range) 69.5 (48-81) 60 (43-90) Hysterectomy indication
Non-malignancy indication 29 (72.5%) 12 (30%)
Malignancy indication 11 (27.5%) 28 (70%)
Body mass index (kg/m2), median (range) 27.1 (19.5-29.8) 25.7 (17.5-29.7) HT/HTSOU, total hysterectomy only or hysterectomy with ovarian conservation; HTSOB, bilateral salpingo- oophorectomy hysterectomy; SD, standard deviation.
Table 1. Characteristics of subjects
Table 3. Paired analysis of blood pressure elevation
Blood Pressure Component Preoperative Six Months
Follow-up p Twelve Months
Follow-up p
All Subjects (n = 80)
Systolic 114.5 (90-137) 120 (90-136) < 0.001* 122 (90-140) < 0.001*
Diastolic 76.5 (60-88) 80 (50-100) 0.099* 80 (60-98) < 0.001*
Mean arterial pressure 89.33 (70-103) 92.5 (70-100) 0.004* 94 (70-108) < 0.001*
Hysterectomy with Ovarian Preservation (HT/HTSOU, n = 40)
Systolic 115.5 (90-137) 120 (100-136) 0.211* 120 (100-136) 0.012*
Diastolic 76 (60-88) 80 (50-100) 0.244* 80 (70-100) 0.004*
Mean arterial pressure 89.5 (71.3-103) 91 (73.3-110) 0.143* 93.3 (60-108) 0.002*
Hysterectomy without Ovarian Preservation (HTSOB, n = 40)
Systolic 114 (90-135) 120 (90-130) < 0.001* 123 (90-140) < 0.001*
Diastolic 77 (60-87) 80 (60-100) 0.329* 80 (60-91) < 0.001*
Mean arterial pressure 89.3 (70-100.3) 93.3 (70-110) 0.006* 95.2 (70-
104.7) < 0.001*
Based on age group
(<40 years, n =48, 40-45 years, n=32) Systolic
< 40 years
40–45 years 110.5 (90-137)
116 (90-136) 120 (90-132)
120 (90-136) 0.002*
0.041* 121 (90-140)
120 (90-136) < 0.001*
0.003*
Diastolic
< 40 years
40–45 years 77.5 (60-87)
75.5 (60-88) 80 (60-88)
80 (50-100) 0.001*
0.107* 80 (60-88)
80 (68-98) 0.001 0.001*
MAP< 40 years
40–45 years 89.7 (70-102.3)
89.2 (70-103) 90 (70-102.7)
93.3 (70-110) 0.036*
0.032* 94 (70-104.7)
93.7 (80-108) <0.001*
<0.001*
* sign indicates p value ≤0.05 means significant or statistically significant.
HT/HTSOU, total hysterectomy only or hysterectomy with ovarian conservation; HTSOB, bilateral salpingo-oophorectomy hysterectomy; MAP, mean arterial pressure.
Blood Pressure Component HT/HTSOU
n (%) HTSOB
n (%) p
Systolic
Preoperative 115.5 (90-137) 114 (90-135) 0.036*
6 months follow-up 120 (100-136) 120 (90-130) 0.992*
12 months follow-up 120 (100-136) 123 (90-140) 0.132*
Diastolic
Preoperative 76 (60-88) 77 (60-87) 0.900*
6 months follow-up 80 (50-100) 80 (60-100) 0.804*
12 months follow-up 80 (70-100) 80 (60-91) 0.228*
Mean arterial pressure
Preoperative 89.5 (71.3-103) 89.3 (70-100.3) 0.350*
6 months follow-up 91 (73.3-110) 93.3 (70-110) 0.618*
12 months follow-up 93.3 (60-108) 95.2 (70-104.7) 0.107*
*Mann-Whitney U Test.
HT/HTSOU, total hysterectomy only or hysterectomy with ovarian conservation; HTSOB, bilateral salpingo-oophorectomy hysterectomy.
Table 2. Blood pressure comparison between study groups
Following the result of characteristic analysis, preoperative and follow-up blood pressure was compared between groups (Table 2). It was known that the initial and follow-up blood pressure was relatively similar between groups.
Based on the analysis, there were no differences in preoperative and follow-up blood pressure components in HT/HTSOU and HTSOB groups. Blood pressure elevation was observed at 6 months and 12 months following hysterectomy. Paired analysis between follow- up examination and preoperative examination can be found in Table 3.
Based on the analysis performed, a significant increase in all blood pressure components can be observed at 12 months after the HT/HTSOU and HTSOB procedures (p <
0.05). Moreover, after six months of the HTSOB procedure, the increase in blood pressure components only occurred in systolic blood pressure and MAP (p < 0.05).
DISCUSSION
This study found that blood pressure elevation can be observed 6 months following hysterectomy, with shorter intervals between the procedure and changes observed in those undergoing without ovarian preservation. The researcher realized that changes in hypertension status according to the criteria of the American Heart Association (AHA) and the European Society of Cardiologists (ESC) could not be assessed within 1 year after hysterectomy [8]. However, it is expected that there will be changes in the blood pressure component during the 1-year monitoring period. Based on previous data, an increase of 20 mmHg systolic or 10 mmHg diastolic was associated with a twofold increased risk of death from cardiovascular disease [9]. In our study, the increase in blood pressure components did not reach the threshold. This might be due to a shorter follow-up period on our study. However, our study showed that the increase in blood pressure components had started to happen as early as 6 months following hysterectomy.
Moorman et al. and Farquhar et al. stated that women with hysterectomy and ovarian conservation experienced menopause earlier, namely 1.9 to 4 years earlier than the average population [10]. However, the effect was more prominent in those having hysterectomy without ovarian conservation. Early menopause might result in increased blood pressure after hysterectomy.
According to the hypothesis of previous studies, women who underwent hysterectomy, with or without ovarian preservation, would have a higher risk of myocardial infarction [11]. When a hysterectomy is performed, the blood flow to the ovaries is reduced, interfering with its function to produce estrogen and prostaglandin (PGI2). Another hypothesis is that the systemic decrease
in PGI2 levels experienced by post-hysterectomy patients will increase the risk of hypertension as higher PGI2 levels are found during the menstrual phase [12,13].
Increased blood pressure components were more severe in HTSOB patients than HT/HTSOU patients. It is well known that estrogen has long-term protective abilities against the cardiovascular system, either naturally through production by the ovaries or administered as supplementation in women who undergo bilateral oophorectomy [14]. In addition, estrogen receptors were found in other organs that regulate blood pressure, such as blood vessels and the kidney. Therefore, the loss of estrogen in young women undergoing oophorectomy is closely related to various health problems [15].
In our study, there was no big difference in blood pressure rate increment of both HTSOU/HT and HTSOB groups throughout the study. Our study showed significant results statistically for both groups, especially at the twelve-month mark. Although the HTSOU group did not show an increment during the 6-month follow-up, hysterectomy without bilateral salpingo-oophorectomy does not mean that it has no side effects. Previous studies have shown that hysterectomy is associated with impaired ovarian blood flow, causing premature ovarian failure due to the loss of collateral blood vessels. It is thought to have the same effect as changes in the vascular system due to hormonal disturbances [5].
The limitation of this study was the lack of confounding variable control. Confounding variables such as the cause of the surgery, diet, and lifestyle could influence the result of this study. Therefore, the result of this study has very limited generalizability. Hence, further study is needed, preferably a prospective cohort of RCT involving more patients undergoing hysterectomy.
CONCLUSIONS
There was a significant increase in all blood pressure components in the HT/HTSOU and HTSOB group at 12 months following hysterectomy while there was a significant increase in systolic blood pressure and MAP in the HTSOB group at 6 months following hysterectomy.
DECLARATIONS
Ethics ApprovalThe Research Ethics Committee of the Faculty of Medicine, University of Indonesia, had approved all human studies with ethical clearance letter number KET-723/UN2.F1/ETIK/2018. All patients included in this study had given informed consent before the study.
Competing of Interest
The authors declare no competing interest in this study.
Acknowledgment
The authors would also like to express sincere gratitude to all participating patients and medical staff in the Department of Obstetrics and Gynecology, Faculty of Medicine Universitas Indonesia – Cipto Mangunkusumo National General Hospital who willingly support this study.
REFERENCES
1. Aarts JW, Nieboer TE, Johnson N, et al. Surgical approach to hysterectomy for benign gynecological disease. Cochrane Database Syst Rev. 2015(8):CD003677.
2. Kallen AN, Pal L. Cardiovascular disease and ovarian function. Curr Opin Obstet Gynecol. 2011;23(4):258–67.
3. CDC. High blood pressure facts [internet]. 2016 [cited 2021 Dec 4]. Available from: https://www.
cdc.gov/bloodpressure/facts.htm.
4. Kementerian Kesehatan RI. Riset Kesehatan Dasar 2013 [Internet]. Jakarta: Kemeterian Kesehatan Republik Indonesia; 2013 [cited 2021 Dec 5]. Available from: https://pusdatin.kemkes.go.id/resources/
download/general/Hasil%20Riskesdas%202013.pdf 5. Ingelsson E, Lundholm C, Johansson AL, Altman D.
Hysterectomy and risk of cardiovascular disease: a population-based cohort study. Eur Heart J.
2011;32(6):745–50.
6. Jacoby VL, Grady D, Wactawski-Wende J, et al.
Oophorectomy vs Ovarian Conservation With Hysterectomy. Arch Intern Med. 2011;171(9).
7. Perhimpunan Hipertensi Indonesia. Konsensus penatalaksanaan hipertensi [Internet]. Jakarta:
Perhimpunan Hipertensi Indonesia; 2019 [cited 2021 Dec 5]. Available from: http://faber.inash.or.id/
upload/pdf/article_Update_konsensus_201939.pdf
8. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/
NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension; 2017.
9. Kovell LC, Ahmed HM, Misra S, et al. US Hypertension Management Guidelines: A Review of the Recent Past and Recommendations for the Future. J Am Heart Assoc. 2015;4(12).
10. Laughlin-Tommaso SK, Khan Z, Weaver AL, et al.
Cardiovascular and metabolic morbidity after hysterectomy with ovarian conservation: a cohort study. Menopause. 2018 May;25(5):483–492.
11. Trabuco EC, Moorman PG, Algeciras-Schimnich A, et al. Association of Ovary-Sparing Hysterectomy With Ovarian Reserve. Obstet Gynecol. 2016;127(5):819–27.
12. Battersby S, Critchley HOD, Brum-Fernandes AJ, Jabbour HN. Temporal expression and signalling of prostacyclin receptor in the human endometrium across the menstrual cycle. Reproduction.
2004;127(1):79–86
13. Nigro RC, Fortes ZB, Carvalho MHC. Effects of estrogen on the vascular system. Brazilian Journal of Medical and Biological Research. 2003; 36: 1143–58.
14. Rivera CM, Grossardt BR, Rhodes DJ, et al. Increased cardiovascular mortality after early bilateral oophorectomy. Menopause. 2009;16(1):15–23.
15. Maric-Bilkan C, Gilbert EL, Ryan MJ. Impact of ovarian function on cardiovascular health in women:
focus on hypertension. Int J Womens Health.
2014;6:131–9.
