SAT-300 Role of Adrenal Progesterone in the Maturation of the Endometrial Lining and Regulation of Menses in Turner Syndrome

Background: In Turner syndrome (TS) with primary ovarian failure (POF), low-dose estrogen (E) therapy (tx) is started at 11-12 years of age, with dose increments over 2-3 years. Progesterone (P) is added once breakthrough bleeding occurs or after 2 years of E tx. Irregular bleeding can occur from unopposed E but both exogenous E and P are necessary for regular menses. In POF, the only source of endogenous P is adrenal. Adrenal steroidogenesis has been postulated to play a role in P increase during the menstrual cycle [1], and LH receptors have been found in the adrenal cortex [2]. In ovariectomized rats, E tx has been found to increase adrenal activity [3]. Objective: To study the effect of endogenous adrenal P on endometrial lining and regulating menses in a case of TS with POF. Clinical Case: An adolescent girl with TS (45X) was diagnosed with POF at 1 month of age (FSH 65.66 U/L, LH 8.31 U/L). At 12 yrs, besides TS stigmata, she had prepubertal breasts and sparse, thin pubic hair with high FSH 88.2 U/L and LH 20.13 U/L. Pubertal induction with transdermal estradiol (TDE) patch was started at 6.25 mcg 2x/wk with dose increments up to 25 mcg 2x/wk over 2 years. At 14.2 yrs, she had Tanner 3 breasts and pubic hair and had menarche. She had 3 irregular periods over the next 6 months with intervals of 1-3 months. At 14.8 years, menses started occurring regularly only on exogenous TDE (FSH 11.3 U/L, LH 5.92 U/L, E 37 pg/mL). Each period would last 3 to 4 days w/ regular flow. At 15 yrs, weekly serum P on day 15 post-LMP showed consistently detectable levels of 0.5, 0.6, 0.7, and 0.6 ng/mL respectively (ref for follicular phase: 0.15-1.4 ng/mL). ACTH stim test showed increase in serum cortisol from 5.2 to 28.5 mcg/dL and serum P from 0.27 to 1.68 ng/mL at 60 mins. US showed uterine size 5.7x1.8x3.5cm and endometrial stripe 11 mm, implying that perhaps the P level was enough to maintain her endometrial lining (day 20 post-LMP). Menses continued at regular intervals of 22-43 days for 12 months on TDE without P replacement. Most recent LH 4.33 U/L, FSH 10.5 U/L, E 67 pg/mL, P 0.64 ng/mL, DHEAS 162 ug/dL. AMH was <0.015 ng/mL and inhibin B <10 pg/mL, consistent with no ovarian function. Conclusion: Although extremely rare, patients with POF may develop regular menses on estrogen therapy without progesterone replacement. Adrenal progesterone may assist in the maturation of the endometrial lining and regulation of menses. 1. De Geyter, C., et al., Progesterone serum levels during the follicular phase of the menstrual cycle originate from the crosstalk between the ovaries and the adrenal cortex. Hum Reprod, 2002. 17(4): p. 933-9. 2. Pabon, J.E., et al., Novel presence of luteinizing hormone/chorionic gonadotropin receptors in human adrenal glands. J Clin Endocrinol Metab, 1996. 81(6): p. 2397-400. 3. Saruhan, B.G. and N. Ozdemir, Effect of ovariectomy and of estrogen treatment on the adrenal gland and body weight in rats. Saudi Med J, 2005. 26(11): p. 1705-9.