Menopause, hrts and diabetes

From time to time we have discussion list members inquiring about how our blood sugar interacts with hormone levels and hrts. Some of these are women who already have diabetes and are worried about how surgical menopause will affect their control; others have newly-diagnosed disease and are wondering why.

Because our ovarian hormones are part of the overall metabolic regulatory system in our bodies, they do affect the functioning of areas that we normally consider outside their regular realm. But just as our thyroid hormone levels interact with the ovarian ones and just as melatonin, the sleep hormone, can be disrupted by the timing of when we take our hrts, so the hormone that regulates our carbohydrate metabolism, insulin, is influenced by our ovarian hormone levels, balance, and fluctuations.

Now, diabetes is a broad term, much like cancer, that loosely covers a variety of distinct diseases that happen to have alterations of carbohydrate metabolism as a common feature. We're not going to go into the various distinctions here—we're not going to talk about diabetes per se, just how it behaves with respect to our ovarian hormones. You can read a basic introduction to the types of diabetes at Wikipedia if you're not altogether sure what we're talking about.

General actions

While many of the details of these metabolic interactions between ovarian hormones and insulin dynamics remain unresearched or the conclusions unclear, the general rule is that normalizing hormone levels to that of post-fertile needs in a stable fashion has the most normalizing effect on blood sugar levels.

This means, yes, that unstable hormones can bring instability to our carbohydrate metabolism and/or diabetic treatment plans. It also means that imbalances in our ovarian hormones can put an additional burden on our treatment or can bias our metabolism in unhealthy ways.

What it does not mean that eschewing hrt in menopause is "better" for diabetic control or that we are "better off" without hrt because it can influence our blood sugars.

Estrogen and insulin

Falling estrogen levels typical of natural menopause are identified by a number of researchers as raising blood sugar and the related risk of diabetes.
Women randomly assigned to hormone therapy had a 35% lower risk for diabetes than those assigned to placebo. This reduction in risk was primarily due to the fact that women in the hormone therapy group maintained a lower fasting glucose level than women in the placebo group. We found that hormone therapy prevented the increase in fasting glucose values that was seen in the placebo group over time. (source)
In nondiabetic women, menopause, but not age, is an independent risk factor for elevated fasting plasma glucose levels (source)
These effects would also be expected to present in surgical menopause, where the estrogen drop is more extreme, and in situations where our hrt is inadequate to raise our estrogen levels to meet our needs. In a rat study, the effect of oophorectomy was summarized thus:
The researchers showed that in older female rats, free of heart disease, estrogen deficiency appears to trigger the development of high blood pressure and obesity.
Rats that had their ovaries removed, thereby depleting their estrogen levels, had significantly higher blood pressure and gained twice as much weight as "control" rats with intact ovaries...
Rats that had their ovaries removed also showed 70-percent higher levels of the fat hormone leptin and 35 percent higher blood sugar levels...
Moreover, female rats without ovaries that receive estrogen replacement therapy do not experience any of these adverse hormonal and metabolic effects (source)
While there's a fair amount of research on estrogen, the picture on progesterone is less well-defined except by extension from the well-known effects on blood sugar of normal menstrual cycling and pregnancy, both of which carry a woman through periods of hormonal imbalance that reflect changing progesterone levels as well as estrogen levels. Thus while it does indeed have an effect, there are fewer clear statements we can point you to.

As a general rule, what we read can be summed up as indicating that progesterone has an effect of increasing insulin resistence. But we are mostly reading that in secondary sources rather than primary ones, and that undermines the authority of these statements. So for now, we have to put that specific relationship in the "probable" column rather than calling it "known."

Hrts and blood sugar

Much of the research that has been done on hrts and diabetes has been done with Prempro or Premarin. But given that different routes of hormone administration can affect how the hormones are actually used in our bodies as well as other associated effects, how can we extend that knowledge to the impacts on blood sugar?

In the Women's Health Initiative Study, the estrogen-only arm found these effects in women with pre-existing cardiovascular disease who took the oral estrogen hrt Premarin (estrogen alone):
  • A slightly smaller number of women who took Estrogen alone developed diabetes but it was not significant when statistical testing was done
  • 8.3% (397 cases/4787 women assigned to E alone) of women who took Estrogen alone developed diabetes over the course of the trial compared to 9.3% (455 cases/4887 women assigned to placebo) of women who took placebo
  • Blood sugar and insulin levels were lower after one year in those women who took Estrogen alone (source)
In contrast, a later study looking at oral as opposed to transdermal summarized these findings:
There was a significant worsening of insulin resistance markers in the oral estrogen group. The team observed significant decreases in glucose-insulin ratio and quantitative insulin-sensitivity check index, and significant increases in baseline insulin and homeostasis model assessment.
Other significant changes in the oral estrogen group included increases in high-density lipoprotein cholesterol and leptin levels, while adiponectin was unchanged. There was also an increase in resistin and a decrease in baseline ghrelin levels.
In contrast, no significant changes in insulin resistance parameters were observed after transdermal estrogen, except for a decrease in the glucose-insulin resistance ratio.
Women in the transdermal group had no changes in leptin or resistin, whereas there were significant increases in adiponectin and decreases in ghrelin levels. No changes in lipid parameters were observed. (source)
In addition to these findings, we know that women with diabetes are at higher risk for both blood clots and cardiovascular disease in general. Since both of these risks are reduced with transdermal hrts as compared to oral (refs), this factor should be taken into account in the hrt route decisions a diabetic woman will make (although they may not be the only factors she'll take into account).

Questions we're asked about menopause and diabetes

Does menopause cause diabetes?

It's hard to attribute direct causation, because many metabolic problems don't necessarily have a clearcut cause the way falling down some steps might directly cause your broken ankle.

What is more likely is that you may have been trending in an unhealthy direction, and the natural impact of menopause or imbalanced hrts just pushed you into the position where you were abnormal enough for the diabetic tendency to be detected.

Will hrt make my diabetes worse? Better?

It depends upon many factors to do with your diabetes, of course, but in general, hrt looks as though it can exert a positive influence. And by hrt, we of course mean effectively-delivered hrt, taken at a dose and balance that fits each woman's individual needs.

It also looks as though hormone stability enhances blood sugar control stability as well. This means that for diabetics, there is extra reason why making changes to hrt in small increments and slowly might be the least upsetting approach.

Looking at if from the other side, it is also probable that if we badly disorder our ovarian hormones through a poor hrt fit, we can disrupt our diabetic control or enhance our odds of progressing to overt disease.

Can I make my blood sugar better by how I adjust my hormones?

Aside from the stability issues discussed above, it doesn't look especially feasible to try to adjust blood sugar using hrt. While tweaking one hormone up or down might alter diabetic treatment amounts needed, the healthiest approach still looks to be adjusting hormones to best needs, and then adjusting diabetic treatment to that stable level.

So it's likely that the most we can do with this information is to raise our awareness that yes, ovarian hormone levels and fluctuations will affect blood sugar and diabetic control, but we cannot generalize from there to any specific measures that will be most effective in any one woman's body. While good ovarian hormone balance can help ease the treatment of diabetes, it's not going to make it go away.

Other practical considerations for diabetics in surgical menopause

One special aspect of using hrt may be especially important for diabetics: the use of vaginal estrogen to prevent vaginal atrophy and maintain healthy urogenital tissues.

Poorly-controlled diabetics are at higher risk for vaginal yeast infections, so it behooves diabetics to take extra care to insure that vaginal estrogen levels are maintained and those tissues are as healthy as can be in terms of their immune function. Don't wait for your doctor to ask you whether or not you're experiencing dryness or libido loss: open discussion as to whether or not your vaginal estrogen levels need supplementation. Recent research suggests that up to 50-60% of postmenopausal women suffer from some degree of vaginal health impairment due to low local estrogen levels, so it's not something special or something to be embarrassed about.

In terms of overall health management, the implications of this inter-relationship are similar to those for women with thyroid disease: alterations in hormone levels and hrt adjustments may well affect blood sugar control and might require adjustments of diabetic therapy in sync with ovarian hormone adjustments.

Further, it's important to keep a close eye on symptoms, because many symptoms of ovarian hormone imbalance may be described in quite similar ways to symptoms of insulin/sugar imbalance. Distinguishing these can be very important to control of both. This is where listening closely to your body is critical. And don't neglect the importance of journalling: keeping track of what we're taking and doing helps us learn to read the signals our body is sending us and we need to take even more care with this the more complex our situation and the factors we are tracking.

And does this have any importance for those of us who are not diabetic?

Oh yeah. The path from being overweight to type II diabetes is a pretty well-established one, especially when we're looking at midbody weight. While to some extent a fat shift to the middle body is a normal part of this menopaused lifestage, it does have a strong risk association with diabetes. It also comes as part of an even less appealing package: metabolic syndrome. So while it is perhaps easier in a head-in-the-sand sort of way to just wait for our doctor to surprise us with the news that our blood sugar lab values are off, it's probably preferable in the long run to take a closer look at our personal risks and modify our diet and, if needs be, hrt so that we are doing as much as we can to prevent diabetes before it gets that far.

And for women who cannot or choose not to supplement their post-menopausal hormone levels, this increased risk is something to keep in mind, both in terms of health maintenance and in terms of specific monitoring in regular checkups. For those who are inclined not to use hrts, this should also be a factor to take into account in that decision, remembering that risk is not all on one side of that evaluation.