PCOS and Menopause – Dr Fiona McCulloch

PCOS is a condition that has long been looked at as a women’s reproductive issue. It has also been unfortunately labeled as an infertility condition. In actuality, it’sa complex endocrine disorder that affects the entire body.

Many people believe that PCOS will go away at menopause, or that having a hysterectomy will cure it.

Nothing could be further from the truth.

Major elements associated with this complex condition include fat cell dysfunction, fatty tissue inflammation, insulin resistance, and androgen excess. PCOS can alsobe associated with autoimmune disorders, cardiovascular disease, type two diabetes, and non-alcoholic fatty liver disease.

That’s a lot more complex than just a “women’s reproductive issue”, isn’t it?

A study found that women with PCOS have a higher amount of visceral fat and metabolic disturbances [1] at late reproductive age. They also have higher LDL cholesterol levels and hypertension.

Although all women do have an increased risk for insulin resistance and more abdominal weight gain during perimenopause, those with PCOS have some essential differences.

Perimenopause and PCOS

First and foremost, those with PCOS have been dealing with insulin resistance for far longer than most other women, as they’ve been secreting more insulin than average for many years.

A recent study[2] backed this up. When it came to perimenopause, there were changes in pancreatic function that differed from those in women without the condition.

In fact, it has been found that at perimenopause, pancreatic beta cells are less functional than they were previously in women with PCOS. The pancreas becomes sluggish after years of producing often-elevated insulin levels.

This means that past menopause, women with PCOS are far more sensitive to sugars, given that they can no longer secrete insulin as effectively to keep it under control. They should be extra careful to prevent diabetes.

Another difference for perimenopausal women with PCOS is a higher number of unexpected pregnancies. These become more common due to preserved fertility. Studies have found that women with PCOS hit their fertile peak and go into menopause on average 2-4 years later than others.

This is due to higher levels of Antimullerian hormone and androgens.Women with PCOS are more likely toconceive in these perimenopausal years, so they need to keep that in mind and take family planning precautions as necessary.

Menopause and PCOS

Diagnostic Difficulties During Menopause

Diagnosing PCOS in perimenopause can also be a challenge.

Since most women with the condition will have normal androgen serum levels by this age, this factor can’t be relied upon as an indicator. The woman’s health history should be taken, with extensive questions about past menstrual cycle regularity and androgen excess signs.

In women with PCOS, androgen levels are still elevated compared to women without it, particularly as they age. Lab ranges don’t reflect age differences, so this trait can often be missed.

We complete urinary hormone metabolite testing in many patients, which makes it easier for us to see androgen excess in older women as well as younger ones.

Another interesting fact is that although adrenal androgen hormone production like DHEA-S typically peak in one’s 20s and decrease with age, there is also a rise in these hormones at menopausal transition.

Four different androgens were tracked and it was found that most women experience a rise in DHEA, DHEA-S, Androstenedione and Androstenediol rise during the menopausal transition. [3]

Hormones in Menopause

The Silver Lining:

One benefit of this transition is that women with higher circulating DHEA appear to sustain cognitive function as they traverse menopause. [4]

There is now evidence that Androstenediol—which has both androgenic and estrogenic activities and is secreted in parallel with DHEAS and DHEA during the menopausal transition—may be the reason.

Androstenediol is thought to be a critical component in menopausal women, and sends signals through both the androgen and estrogen receptors. [5]The downside of this is that increased levels of adrenal androgens often trickle down into increased testosterone levels as well.

Once the menopausal transition is complete, these levels will decrease in time—typically around two years after the last menstrual period. [6]

The increase in DHEA-S that starts in early perimenopause and continues into early post-menopause result in Androstenediol concentrations that are around 100 times the average estradiol concentrations. (Estradiol is the strongest form of estrogen.)

Even though Androstenediol acts weakly as an estrogen, its increased concentration at this time have been shown to elicit an estrogenic response. This temporarily protects women with PCOS from the impacts of estrogen loss, especially on the skin and brain.

What to Monitor in Meopause

What to Keep an Eye On:

Interestingly, women with PCOS have fewer hot flashes and menopausal symptoms than women without the condition, but they do experience more hirsutism. [8]

Women with this condition also present risk factors for endometrial cancer, but not for breast or ovarian cancer. [9]

What should you monitor in PCOS in Perimenopause and after menopause?

  1. Insulin resistance. This is linked to abdominal weight gain, fatty liver, and diabetes risks.See here for a comprehensive guide to testing for insulin resistance and prediabetes.
  2. Serum DHEA-S, Total testosterone and Androstenedione
  3. Serum DHT(Dihydrotestosterone levels) particularly if hair loss or hirsutism is an issue
  4. Urinary androgen metabolites including Androsterone, DHEA-S, 5-a-DHT and Etiocholanolone
  5. Inflammation – hs-CRP. Linked to all chronic aging processes.
  6. ALT – A marker of fatty liver disease
  7. Cholesterol panel especially triglycerides and LDL particle size
  8. Vitamin D – Important for metabolic and immune health. Deficiency in this vitamin is associated with most chronic disease risk in PCOS.
  9. Thyroid hormones including antibodies. Women with PCOS are at an increased risk of Hashimoto’s thyroiditis and so need to watch their thyroid more carefully.
  10. Blood pressure – Since women with PCOS are more prone to hypertension, they should monitor their blood pressure.
  11. Sleep apnea – A sleep study is often a good idea, as there is an increased risk of sleep apnea in PCOS. Research shoes that the prevalence of sleep apnea increases with age due to increased fatty deposits in the head and neck area. [10] A common symptom of sleep apnea is waking to urinate at night. This is because as you have difficulty breathing, pressure increases in the chest. Hormones that cause frequent urination are released, hence why you may wake at night to relieve yourself.

Article References:

  1. Ramezani Tehrani F, Minooee S, Azizi FComparison of various adiposity indexes in women with polycystic ovary syndrome and normo-ovulatory non-hirsute women: a population-based studyEuropean journal of endocrinology / European Federation of Endocrine Societies2014;171:199-207.
  2. Echiburú, B., Crisosto, N., Maliqueo, M., Pérez-Bravo, F., de Guevara, A. L., Hernández, P., … Sir-Petermann, T.Metabolic profile in women with polycystic ovary syndrome across adult lifeMetabolism2016;65(5):776-782.https://doi.org/10.1016/j.metabol.2016.01.006
  3. Lasley, B. L., Crawford, S., McConnell, D. S.Adrenal androgens and the menopausal transitionObstetrics and Gynecology Clinics of North America2011;38(3):467-75.https://doi.org/10.1016/j.ogc.2011.06.001
  4. SEYMOUR-MUNN, K., ADAMS, J.Estrogenic Effects of 5-Androstene-3β,17β-Diol at Physiological Concentrations and Its Possible Implication in the Etiology of Breast Cancer*Endocrinology1983;112(2):486-491.https://doi.org/10.1210/endo-112-2-486
  5. Crawford, S., Santoro, N., Laughlin, G. A., Sowers, M. F., McConnell, D., Sutton-Tyrrell, K., … Lasley, B.Circulating Dehydroepiandrosterone Sulfate Concentrations during the Menopausal Transition
  6. Stimulation of cell proliferation and estrogenic response by adrenal C19-delta 5-steroids in the ZR-75-1 human breast cancer cell line.Poulin R, Labrie F,Cancer Res1986 Oct; 46(10):4933-7
  7. Schmidt, J., Brännström, M., Landin-Wilhelmsen, K., Dahlgren, E.Reproductive hormone levels and anthropometry in postmenopausal women with polycystic ovary syndrome (PCOS): a 21-year follow-up study of women diagnosed with PCOS around 50 years ago and their age-matched controlsThe Journal of Clinical Endocrinology and Metabolism2011;96(7):2178-85.https://doi.org/10.1210/jc.2010-2959
  8. Barry, J. A., Azizia, M. M., Hardiman, P. J.Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysisHuman Reproduction Update2014;20(5):748-758.https://doi.org/10.1093/humupd/dmu012

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