Progesterone is initially produced by the “corpus luteum” which is the leftover follicular structures on the ovary after ovulation. After implantation of the embryo it is produced by the placenta. Progesterone is essential for proper development and support of the endometrium which is the lining of the uterus.
The endometrium must thicken and become more vascular to provide nourishment to the developing embryo/fetus. Insufficient progesterone, sometimes termed a luteal phase defect, is treated successfully with progesterone medication given by injection or other routes. Progesterone injections are commonly administered in IVF and donor egg cycles since the drugs used for treatment (Lupron, Ganirelix, Cetrotide) interfere with the body’s normal production of progesterone.
Metformin belongs to a category of drugs known as insulin sensitizing agents used to treat type II diabetes. These patients have chronically elevated insulin levels (hyperinsulinemia) and metformin increases the pancreases sensitivity to insulin thus decreasing hyperinsulinemia and causing insulin levels to return to normal.
PCOS is a common cause of female infertility and it is characterized by elevated androgens (male hormones), elevated insulin levels, increased body hair, irregular or no ovulation, ovaries covered with unruptured cysts and other symptoms. Once the abnormally high androgen levels in the PCOS patient are reversed, ovulation will often resume. Metformin accomplishes this by correcting hyperinsulinemia which ultimately leads to reduced androgen production by the ovaries.
Metformin’s mode of action is different from drugs such as Clomid and FSH. Metformin corrects a physiologic abnormality allowing normal ovulation to resume whereas Clomid and FSH (albeit different mechanisms) effect the hypothalamic pituitary adrenal axis causing increased production of follicle stimulating hormone.
Metformin has been shown to be effective in treating PCOS and has also been used in combination with FSH or Clomid. Additionally, continued metformin treatment lowers the risk of conditions that accompany hyperinsulinemia as these patients age, such as cardiovascular disease and diabetes.