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Diabetes and polycystic ovary disease
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A 32-year-old black woman came to see me for secondary amenorrhea that had lasted for four years. The patient had been prescribed courses of medroxyprogesterone every six months by her gynecologist to induce menstruation. This was usually successful and ended with a strong menses. However, her last treatment had been more than a year ago and she had not had any menstruation or other bleeds since.
 Ronald Tamler |
The patient had been trying to intentionally lose weight. She weighed 250 lb one year prior to seeing me, then gained weight to 280 lb, and now weighed 266 lb after watching what she was eating. Menarche had started at age 11 and had always been somewhat irregular. She had one healthy 8-year-old child, and she and her boyfriend were hoping to have a second child as soon as possible.
She denied acne or virilized hair pattern. When asked, the patient confirmed polydipsia, polyuria and fatigue. A recent pelvic ultrasound had demonstrated multiple cysts in both ovaries. The report did not mention the thickness of the endometrial echo stripe. Other medical history consisted of asthma and C-section. The patient stated allergies to iodine and seafood. Medication use included albuterol and fluticasone/salmeterol inhalers.
Family history was remarkable for ovarian cancer in the grandmother and diabetes and hypertension in the patient’s mother. Smoking, alcohol and recreational drug use were denied.
On physical exam, this was an obese black woman in no acute distress. Pertinent findings included a weight of 266 lb, height of 65 in, and BMI of 43. Her heart rate was 78 and blood pressure was 130/88 mm Hg. She had acanthosis nigricans. The thyroid was of normal size and smooth. There was no evidence for male-pattern body or facial hair, no acne, no male-pattern parietal hair loss.
Blood glucose level four hours after the last meal was at 148 mg/dL in the office. HbA1c was 6.4%. Luteinizing hormone was 12 mIU/mL, and follicle-stimulating hormone was 7.8 mIU/mL, total testosterone 82 ng/dL (upper limit is 70), 8, 10, estradiol 38, progesterone 0.26. Thyroid stimulating hormone, prolactin, 17-hydroxy-progesterone DHEAS, androstenedione, 24 hour urine cortisol were normal. Two hour OGTT with 75 g: fasting 107 mg/dL, 203 mg/dL after two hours.
After a brief course of medroxyprogesterone to induce menstruation, several treatment options remain.
Which of the following would be least useful for this patient, who is actively trying to conceive?
- Referral to a nutritionist and increase in physical activity.
- Start metformin and uptitrate. If the patient has not had a period in more than three months, start exenatide 5 mcg twice a day.
- Refer the patient to a bariatric surgeon for an evaluation.
- Start finasteride and spironolactone.
- Start pioglitazone and orlistat.
CASE DISCUSSION
This woman not only has polycystic ovary disease, with secondary amenorrhea, high androgen levels and ovarian cysts on ultrasound, but she also has type 2 diabetes. PCOS is often connected to obesity and diabetes or prediabetes.
Ideally, we would find her a regimen that would treat her diabetes and enable her to have a regular cycle, with the chance to conceive another child. An important first step consists of lifestyle changes that are aimed to reduce weight by 5% to 10% in a controlled fashion, in this case 13 lb to 26 lb (option A). This degree of weight loss would not only improve insulin resistance, but may also help induce ovulation.
The patient was referred to our nutritionist and started working out at a gym, with modest success. At a BMI of >40, she would also qualify for bariatric surgery (option C), which would address both problems. Evaluation for the surgery often takes time, and patients need to document their failed attempts to lose weight with other modalities. While it is unusual to refer a patient with diabetes at the time of diagnosis, early referral should nonetheless be considered.
Thiazolidinediones, such as pioglitazone, have been shown to help not only with diabetes, but also in patients with PCOS. They are, however, infrequently prescribed for PCOS and may cause additional weight gain. Orlistat may help the patient lose weight and has also been shown to help induce normal menstrual cycles in PCOS.
Both finasteride and spironolactone have been used in women with PCOS to address acne and other symptoms of virilization. They have no effect on diabetes. They can act synergistically with oral contraception, which also should be prescribed to avoid teratogenic effects. This regimen should not be administered to women trying to conceive.
In this case, I started the patient on metformin. Unfortunately, I was unable to uptitrate beyond 750 mg daily due to gastrointestinal symptoms. While blood glucose levels improved, the patient still was amenorrheic. I then started her on exenatide. She experienced mild weight loss of 6 lb, and finally had a period along with molimina, indicating that an ovulation had taken place. Exenatide does not have an indication from the FDA for PCOS, but a recent publication by Elkind-Hirsch et al demonstrated astounding results in combination with metformin.
Ronald Tamler, MD, PhD, MBA, is an Assistant Professor in the Division of Endocrinology at Mount Sinai School of Medicine, N.Y.