Kidney Coach

The Link Between Menopause & Chronic Kidney Disease

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hormones and menopause and the link to renal disease

‘Natural menopause is deemed to have occurred after 12 consecutive months without menstruation for which there is no other obvious physiological or pathological cause and in the absence of clinical intervention.’

After working with many women in this area of health, symptoms can be confusing and debilitating and can impact how we see ourselves and our lives. It can be a trying and challenging transition for not only those affected but also loved ones and can persist for quite a few years.

Key Points on Menopause

  1. Menopause marks the end of a woman’s reproductive years.
  2. Most women experience menopause between the ages of 45 and 55 as a natural part of biological aging.
  3. Menopause is caused by the loss of ovarian follicular function and a decline in circulating blood oestrogen levels.
  4. Transition can be very gradual and usually begins with changes in the menstrual cycle.
  5. Perimenopause is an important period in which these changes occur. This stage ends one year after the final menstrual period. Perimenopause can last several years and can hugely impact women’s mental, emotional, physical and social well-being.
  6. Menopause can be a consequence of surgical or medical procedures.

There are Three Major Forms of Estrogen:

Estrone (E1)- Estrone is the primary form of estrogen produced by the body after menopause.

Estradiol (E2)- Estradiol is the most potent form of estrogen; it dominates in the reproductive years.

Estriol (E3)- Estriol is predominant during pregnancy; it supports foetal development.

Symptoms That Will Flag Kidney Function Investigation During This Transition

  • Rapid weight gain
  • Increase in inflammatory response
  • Hypertension

oestrogen and menopause and kidney disease

Source Hormone Health: Estrogen Metabolism – The Good The Bad and the Ugly – Absolute Health & Wellness (absolutehealthparis.com)

The Role of Estrogen

Estrogen is an important reproductive hormone with wide-ranging effects that extend far beyond reproductive health. Within the reproductive system, estrogen is essential in regulating the menstrual cycle. It supports the growth and maintenance of the endometrium during the first part of the cycle, preparing our body for a potential pregnancy.

During puberty, estrogen is responsible for the development of secondary sex characteristics, such as the development of breast tissue, widening of hips and pubic/underarm hair.

During pregnancy, estrogen levels rise to support foetal development, regulate other hormones, and prepare the body for birth.

However, estrogen has also been found to play a role in other areas of the body, and they are as follows:

Bone Health

Estrogen regulates bone metabolism and helps maintain bone density. It is essential for bone health as it promotes the activity of osteoblasts, these are the cells that make new bone. When estrogen levels fall, such as during menopause, bone density can be lost. This makes bones more fragile and brittle, making you more susceptible to fractures.

Estrogen influences osteocytes as well as osteoblasts and osteoclasts. As estrogen levels reduce, the way these cells function is affected; it causes them to produce too little new bone and not properly maintain bone structure.

How does estrogen affect osteoporosis? (medicalnewstoday.com)

Cardiovascular Disease

Estrogen has a protective effect on the cardiovascular system. It helps maintain healthy cholesterol levels by increasing HDL (good cholesterol) and decreasing LDL (bad cholesterol). Estrogen promotes the dilation of blood vessels, which has a positive effect in reducing blood pressure and blood flow, healthy blood flow is essential for optimal heart function. Estrogen also helps deal with free radicals which have the ability to damage arteries and other tissues.

How Estrogen Impacts Heart Health (clevelandclinic.org)

Brain and Mood

Estrogen has an impact on cognitive function and mood. One of the main influences estrogen has on the brain is its ability to increase and improve the neurotransmitters serotonin and dopamine function. Estrogen can modify the effect of endorphins and have a neuroprotective effect. During perimenopause, the withdrawal of estrogen levels has been linked to mood swings, depression and anxiety.

Using ovariectomized animals, research has identified estrogen-induced changes in serotonin transmission, binding, and metabolism in brain regions implicated in cognition. Studies in mostly postmenopausal women undergoing estrogen treatment have shown some support for these findings, as there have been identified incidences where changes in mood and cognition are correlated with alterations in serotonin function and hormonal status.

Effect of estrogen-serotonin interactions on mood and cognition – PubMed (nih.gov)

estrogen and kidney disease

Image via Women’s Healthcare – Dr. Yousuf Siddiqui, ND – Natually (dryousufnd.com)

Menopause & CKD – The Link

There is growing interest in the correlation between CKD and menopause. The decline in estrogen levels seen in menopause, coupled with the physiological changes associated, suggests that hormones may influence the development and progression of KD.

Estrogen Plays a Protective Role on the Kidneys

Estrogen has a protective effect on the kidneys. It helps to maintain endothelial function, reducing oxidative stress and modulating the inflammatory response. The mechanisms responsible for the protection of kidneys due to estrogen is not completely understood. However, research suggests it’s due to induced vasodilation in the renal vessels, leading to enhanced production of nitric oxide (NO), reducing inflammation and ischemia mediators. It has been shown that estrogen stimulates the release of NO, which results in vasodilation. A NO deficiency can be associated with increased kidney injury due to reduced vasodilation and endothelial dysfunction. Studies also show estrogen decreases the synthesis of renin and angiotensin-converting enzyme (ACE) and increases angiotensinogen synthesis. Experimental studies have shown that the administration of continuous estradiol can prevent glomerulosclerosis and albuminuria.

A 15-year prospective cohort study found woman with higher levels of endogenous estrogen exposure (EEE) had a lower incidence of CKD. EEE was calculated on factors such as age at menarche, pregnancies, lactation, oral contraceptive use and age at menopause.

Endogenous estrogen exposure and chronic kidney disease; a 15-year prospective cohort study | BMC Endocrine Disorders | Full Text (biomedcentral.com)

Estrogen has also been shown to participate in the regulation of phosphorus homeostasis through its receptors in the proximal tubule. The effects of estrogen in physiological and pathophysiological conditions are mediated by two different structural receptor classes, mainly;

  1. Estrogen receptor (ER) α/β
  2. G protein-coupled estrogen receptor (GPER)

Recent experimental and clinical studies have suggested that estrogen and ERs serve pathophysiological rolls in KD.

This includes;

  • AKI
  • Diabetic kidney disease
  • Lupus nephritis
  • IgA nephropathy
  • Other complications of CK

Estrogen and estrogen receptors in kidney diseases – PMC (nih.gov)

Estrogen and the Cardiovascular System

Menopause can be associated with an increase in blood pressure, this is thought to be partly due to the loss of estrogen’s vasodilatory effects. Hypertension is a major risk factor for CKD as it can cause damage to the blood vessel within kidneys, impairing their ability to filter blood effectively.

After menopause, a woman can be more likely to develop metabolic syndrome. Metabolic syndrome is characterised by abdominal obesity, high triglycerides, low HDL cholesterol, high blood pressure and high blood sugar. Metabolic syndrome increases the risk of stroke, heart disease, and type 2 diabetes, all adding load onto the kidneys. The decline in estrogen during menopause is associated with unfavourable lipid profiles. This is characterised by an increase in LDL and decreased HDL cholesterol. These changes are seen to be significant risk factors for cardiovascular disease. Arteries become more vulnerable to disease as they become thicker and stiffer, further contributing to the risk of CVD and kidney disease.

The connection between menopause and cardiovascular disease risks | American Heart Association

Estrogen and Diabetes

Due to the fall in estrogen, changes can be seen in insulin sensitivity, which raises the risk of type 2 diabetes. Blood sugar levels can change more than previously experienced. If blood sugar levels become out of control, there is a higher risk of diabetes complications. Weight gain is commonly associated with menopause, which is a known risk factor for type 2 diabetes. Disturbed sleep due to excess heat has also been linked with an increased risk of diabetes.

Age

Age itself can be associated with the increased risk of KD. Since menopause typically occurs during midlife, it coincides with the age-related risk factors in CKD.

Estrogen and Inflammation

Estrogen has been found to have both pro and anti-inflammatory effects depending on the situation. Generally, low estrogen increases the levels of reactive oxygen species (ROS) and activates nuclear factor-κB and pro-inflammatory cytokine production, indicating their anti-inflammatory properties. However, estrogen’s impact on inflammation varies based on the situation, so it cannot be classified as solely proinflammatory or anti-inflammatory.

Changes in Klotho Levels

Klotho levels are closely related to age. Its serum level is low in the first decade; it then increases and peaks in the 20-40 age group and gradually decreases. In humans, klotho deficiency has been associated with the development of atherosclerosis, diabetes, high blood pressure, chronic kidney disease, osteoporosis, anaemia, and various cancers. Most of the klotho in the body is produced in the kidneys, which means that the more kidney damage you have, the less klotho they can make, which then results in further damage, which becomes a bit of a vicious cycle.

Low levels of klotho contribute to the progression of kidney disease not only by directly affecting the kidneys themselves but also by contributing to the development of cardiovascular disease, high blood pressure and diabetes. Investigating Klotho levels can reduce the probability of kidney disease a long time before it occurs.

Is Klotho the new Superstar in Kidney Disease? – Kidney Coach

Complex Role of Estrogens in Inflammation | Endocrine Reviews | Oxford Academic (oup.com)

Estrogens, osteoarthritis and inflammation – PubMed (nih.gov)

Hopefully, you can now see the link between menopause and the increased risk of CKD. This link is associated with and influenced by hormonal changes, age-related factors and comorbid conditions. Studies show that the decline in estrogen during menopause contributes to these risks by making women more susceptible to hypertension, insulin resistance and changes in lipid profiles, all of which are major risk factors for CKD. Adding to this, there are metabolic changes associated with menopause, such as increased central obesity and a pro-inflammatory state, further exacerbating the risk of kidney damage. The above information highlights the need to assess kidney function in this population, especially when flagged symptoms are experienced. Maintaining a healthy diet, regular exercise, stress management, and management of weight, blood pressure, and blood sugar levels is crucial for kidney and reproductive health. Understanding this link can lead to better prevention and management strategies to improve the health and quality of life in menopausal women.

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