Polycystic Ovary Syndrome: Drug Therapy

Therapeutic target

Reduction of androgen formation in the ovaries and/or adrenal cortices.

Therapy recommendations

Therapy recommendations are based on the patient’s wishes, as well as the clinical symptoms that are in the foreground:

  • Anticonception request
  • Skin symptomatology (acne, alopecia, hirsutism).
  • Insulin resistance / metabolic syndrome
  • Desire to have children
  • Cycle regulation

The type of therapy, whether local or systemic, depends on the severity of androgenization and the patient’s situation (premenopausal, with or without desire for children or contraception, or postmenopausal). There are no generally binding guidelines for therapy. Diet and exercise should be at the forefront of therapeutic measures! Often, weight reduction alone already leads to a normalization of the cycle and follicle maturation (egg maturation); significant improvements in follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), total testosterone, androstenedione, free androgen index and FG score (Ferriman-Gallwey score for quantifying hirsutism/increased androgen-dependent hairiness) are seen. If contraception is desired, a combined hormonal contraceptive (estrogen-progestin combination) with an antiandrogenic progestin is recommended as initial preparation. If contraception is contraindicated or not desired, antiandrogens such as spironolactone or finasteride (contraindicated in pregnancy) can be used. If the patient wishes to have children, these reduce free testosterone levels until the onset of gravidity. If the effect is insufficient, a combination of several preparations may be necessary or useful, e.g. estrogens with an antiandrogenic progestogen and the non-steroidal adrogen receptor blocker finasteride or the aldosterone antagonist spironolactone. Metformin (drug from the biguanide group) is now considered the drug of first choice in PCO syndrome and metabolic syndrome to improve insulin resistance (reduced effectiveness of the body’s own insulin at the target organs skeletal muscle, adipose tissue and liver). Weight loss averages about 6-10 kg in 6 months. Furthermore, metformin results in lowering systolic blood pressure, triglycerides, and increasing HDL cholesterol. Notice:

  • Metformin in pregnancy increases child body weight: in the metformin group, 26 children (32 percent) were overweight or obese at four years of age compared with 14 children (18 percent) in the placebo group, according to one study.
  • Metformin use in the 1st trimester (third trimester of pregnancy) leads to increased risks for adverse pregnancy outcomes only in the presence of preexisting diabetes:
    • When all indications are included – compared without metformin exposure: increased rate of congenital malformations (5.1% versus 2.1%) and miscarriages and abortions (20.8% versus 10.8%)
    • With known diabetes mellitus – compared to all unexposed: increased rate of congenital malformations (7.8% versus 1.7% (n. s.)) and miscarriages and abortions (24.0% versus 16.8% (n. s.))

In cases of childbearing based on the opinion of the German Society of Gynecology and Obstetrics (DGGG) and the German Society of Gynecological Endocrinology and Reproductive Medicine (DGGEF):

  1. If obesity is present with insulin resistance, the first step is moderate weight loss. In exceptional cases and with pronounced insulin resistance, metformin can be given concomitantly to improve insulin sensitivity.
  2. If weight loss in PCOS patients with obesity is not sufficient to achieve ovulatory cycles, stimulation is given with clomiphene.
  3. If the patient shows clomiphene resistance, stimulation is done with FSH.
  4. If insulin resistance is present without obesity, metformin is started directly.
  5. If there is no insulin resistance, is stimulated directly with clomiphene.
  6. Metformin administration in PCOS without insulin resistance? Since there is initial evidence of direct effects of metformin, metformin can be given alternatively in all PCOS patients as a trial and error trial.
  7. Based on the meta-analyses by Palomba and Tso, additive metformin administration should be considered in the context of artificial insemination therapies to reduce the risk of OHSS.

In late-onset AGS (adrenogenital syndrome), glucocorticoids are the drug of first choice. See also under “Further Therapy.”