Progesterone Resistance

Description

Progesterone prepares the endometrium for blastocyst implantation and allows maintenance of pregnancy. The major sources of progesterone are the corpus luteum during the second half of the menstrual cycle and at the beginning of pregnancy, and the placenta. The main hormones responsible for stimulation of progesterone secretion are luteinizing hormone (LH) for the corpus luteum of the menstrual cycle and chorionic gonadotropin for the corpus luteum of pregnancy. Complete end-organ resistance to progesterone would be incompatible with reproductive competence in females. Males would not be expected to be affected since progesterone has no known function in men. Failure of the uterus to respond to progesterone would lead to the development of a 'constantly proliferative' endometrium incompatible with blastocyst implantation. Partial resistance to progesterone, on the other hand, would be expected to be associated with various degrees of incomplete maturation of the endometrium, perhaps expressed clinically as infertility or early abortions. The syndrome would present with the clinical and histologic picture of a luteal phase defect in which the life span of the corpus luteum and the plasma progesterone concentrations would be normal or elevated.

Clinical Features

The first report of a well-studied patient with progesterone resistance was by Keller et al. (1979). Their patient was an infertile woman with a normal menstrual cycle, a normal luteal phase duration, and normal plasma immunoreactive LH and progesterone concentrations. The endometrium was histologically immature. A decreased concentration of endometrial progesterone receptors (PGR; 607311) on day 14 of the luteal phase of the menstrual cycle was suggested by the studies.

Chrousos et al. (1986) stated that the patient of Keller et al. (1979) was the only one in whom progesterone receptors had been examined; however, a similar defect had been proposed in other patients. Compensated progesterone resistance due to reduced progesterone receptor concentrations has been found in female squirrel monkeys and other New World primate species (Chrousos et al., 1986).

Molecular Genetics

Although the progesterone resistance syndrome may be due to mutations in the progesterone receptor gene, Chrousos (2002) stated that none such had been identified to that time.