PCOS and Metformin

Insulin Sensitizers

The newer treatments for PCOS aim at the root cause – elevated insulin levels.  Insulin sensitizers are intended to help the body begin to effectively process insulin again.  These medications were originally prescribed to people with type II diabetes but have also been shown to successfully treat women with PCOS who have insulin resistance. Let’s use the door-and-key analogy again.  Insulin sensitizers help the body rediscover the key to unlock the cell doors, allowing the entry and storage of excess glucose. As insulin and glucose levels return to normal, the ovary resumes normal function, and many of the other hormones return to a more appropriate level.  In turn, many PCOS symptoms diminish.  For many women, insulin sensitizers restore menstrual cycles and alleviate such symptoms as hair growth on the body, thinning hair, acne, and excess weight.  Insulin sensitizers lower the risk of cardiovascular disease and diabetes.  These medications ay also cause insulin-resistant women to start ovulating again.

If you are taking insulin sensitizers, report any changes in your monthly cycle to your doctor.  In addition, let your health-care provider know if you are trying to become pregnant, are already pregnant, or are breast-feeding.  Side effects of insulin sensitizers are rate. Although these medications lower elevated blood sugar levels in people with diabetes, when given to women with high insulin levels, they only lower insulin levels.  Blood sugar levels will not change; therefore, women will not experience episodes of “low blood sugar.”

Because research has indicated that some insulin sensitizers might cause liver problems, your physician should monitor your liver function by conducting periodic blood tests as a precaution is any of the medications are prescribed for you.

Call your health-care provider right away if you develop nausea, vomiting, stomach pain, loss of energy or appetite, dark urine, or jaundice (yellow coloring of the eyes and skin).  These may be symptoms of potential liver problems.


Metformin (Glucophage)

One insulin sensitizer, metformin, whose brand name is Glucophage, seems to alleviate PCOS symptoms for many.  It is not approved by the FDA to treat PCOS, but is approved as a treatment for diabetes; it has been found to lower insulin levels.

Approximately 30 percent of patients started on Glucophage will experience gastrointestinal symptoms: diarrhea, nausea, vomiting, abdominal bloating, flatulence, and loss of appetite.  These symptoms are usually temporary (one to four weeks) and will disappear during continued therapy.  It is advisable for new patient to initiate therapy slowly to minimize the gastrointestinal side effects.

“As a nurse, I can tell you that almost everyone who goes on this develops GI (gastrointestinal) symptoms to some degree,” said Julie.  “My endocrinologist said, “Take this with food to avoid the GI upset.”  I found I did best by taking the metformin halfway through the meal.  The food ‘cushions’ the pill, and the GI upset is lessened or in many cases eliminated.  You may have diarrhea or nausea regardless of what you do for approximately seven days minimally, so don’t give up if that happens. Keep doing it and you’ll see a significant improvement.”

PCOS Treatment and Metformin

As discussed previously, PCOS is also often associated with insulin resistance high blood insulin levels (hyperinsulinemia) and non-insulin dependent Diabetes mellitus which could play a key pathogenic role in its development, contributing to the development of obesity, an abnormal lipid profile, and cardiovascular disease. Women with PCOS are also at a slightly increased risk of developing uterine, ovarian and possibly also breast cancer and accordingly should be evaluated carefully on an annual or more frequent basis.

There has in recent years been a flurry of interest in the possible benefits of using metformin, (brand name Glucophage) to treat women with PCOS in the hope of improving ovulation function, restoring menstrual cycles, reducing the effects of male hormones and improving fertility potential. It has also been speculated that metformin, by lowering blood insulin levels and regulating cellular metabolism, might reduce the long term risks of heart disease, stroke and diabetes mellitus in women in women with PCOS.  So, what is really known about the potential benefits of metformin who take it for 3-6 months with regard to treating PCOS in general, and enhancing fertility in specific?

The following beneficial effects are known.

  1. 50% of women with irregular periods and about 25% of women with absent periods will experience a restoration of normal menstrual cycles.
  2. In about 25% of cases, ovulation is restored with 10% of the women conceiving spontaneously within a 6 month period of treatment.
  3. In most cases where the blood testosterone level is raised, there will be about a 30% reduction in serum testosterone levels within 3-6 months..  It is believed that this feature of metformin activity could play an important role in improving ovulation function and/or response to fertility drugs (such as clomiphene citrate and/or gonadotropins) as well as accounting for a modest reduction in side effects of male hormones (5-8%).

Metformin’s mode of action probably relates to an improvement of the blood insulin level by decreasing bowel absorption of glucose, improving glucose uptake into the cells and increasing the number of insulin receptors on the surface of cells.

PCOS patients who have the following features represent the ones that are most likely to benefit from metformin therapy:

•    Raised serum insulin levels or insulin resistance.
•    Irregular rather than absent menstrual periods.
•    Raised serum testosterone levels.
•    An LH/FSH ratio greater than 2:1.

Metformin therapy can be used safely in conjunction with IVF in women with insulin resistance.  There is no evidence that it is harmful if taken during pregnancy.  Frequently, the side effects (mainly diarrhea) are worse with the initiation of treatment and improve with time as the patient gets used to the medication. Since obesity is frequently an important component of the condition of PCOS, and invariably, patients who need metformin tend to be more obese than those who do not, it is worth mentioning the following points:

  1. Due to obesity, there are significant changes in hormonal metabolism, caused by the peripheral conversion in the fat male hormones to estrogens.  This tonic feedback of estrogen to different regions of the brain, can interfere with the normal processing and functioning of the brain with respect to other hormones.
  2. Insulin resistance is much worse in obese compared with non obese patients — the reason for the metformin in the first instance.
  3. PCOS is associated with significant changes in lipid metabolism and alterations in lipid profiles, with associated worsening of the risks of coronary artery disease/heart attacks.

For all of these reasons, weight reduction is a very important part of the overall management of patients with PCOS.  The usual methods are diet and exercise.  It boils down to simple mathematics of the numbers of calories ingested in the diet, minus those that are burned (by exercise).  Therefore, getting on a regular exercise program is pivotal in the management of the patient with PCOS.  However, in recognition for the fact that weight reduction is not easy and appreciable weight loss is not readily achieved, we refer to www.mydiet.com. For Spanish language diet information please seewww.midieta.com.  These sites are dedicated to the management of obesity addressing all aspects of this condition.  We comment on obesity elsewhere in this website as well.

Other Treatment of PCOS

Ovulation induction with clomiphene progressing to gonadotropin often with insemination is highly successful in cases of infertility. These specific treatments are outlined elsewhere on the website. However some patients require IVF treatment.