A 35-year-old G0P0000 woman presents to her gynecologist with complaints of irregular menstruation. She has had only 2 periods in the last year. She feels flushed without provocation and is experiencing occasional dyspareunia with post-coital spotting. She has also had more frequent headaches than usual. The patient has a medical history of Hashimoto thyroiditis and takes levothyroxine daily. Her mother has type 1 diabetes mellitus. Her temperature is 98.5°F (36.9°C), pulse is 70/min, blood pressure is 118/76 mmHg, and respirations are 13/min. Cardiopulmonary and abdominal exams are unremarkable. The patient has Tanner 5 breasts and pubic hair. A pelvic exam reveals a normal cervix, an anteverted uterus without tenderness, and no adnexal masses. The following laboratory studies are performed: Serum: Thyroid stimulating hormone (TSH): 28 µIU/mL (9-30 µIU/mL) Cycle day 3 follicle stimulating hormone (FSH): 49 mIU/mL (4.7-21.5 mIU/mL) Cycle day 3 estradiol: 8 pg/mL (27-123 pg/mL) Prolactin: 14 ng/mL (4-23 ng/mL) Testosterone: 42 ng/dL (15-70 ng/dL) Which of the following is the most appropriate next step in management?
Combined oral contraceptive
Increase levothyroxine dose
Brain MRI
Estradiol patch with oral medroxyprogesterone
Estradiol patch with oral medroxyprogesterone
This patient presents with oligomenorrhea, hot flashes, and dyspareunia, and her labs are notable for a high FSH and low estradiol, most consistent with premature ovarian insufficiency/failure (POI). The most appropriate next step in management is an estradiol patch with oral medroxyprogesterone.

POI is defined by the depletion or dysfunction of ovarian follicles, resulting in oligomenorrhea or amenorrhea with symptoms of menopause (hot flashes, vaginal atrophy and dryness, mood swings, etc.) in women under age 40. The cause is unclear and thought to be autoimmune. The main diagnostic markers are a high FSH and low estradiol at the start of the follicular phase. Patients require estrogen supplementation until around age 50, as low estrogen increases the risk of coronary artery disease, osteoporosis, and sexual dysfunction. Vaginal gel or a transdermal patch is the first-line option, but both must be used in conjunction with medroxyprogesterone to avoid unopposed estrogen and the risk of endometrial hyperplasia.

Tsiligiannis et al. review the evidence regarding the outcomes of patients with POI. They discuss how this diagnosis is made in patients younger than the age of 40. They recommend closely managing the cardiovascular risk factors associated with this disease.

Incorrect Answers:
Answer A: Brain MRI would be useful for evaluating for the presence of a prolactinoma, which could cause the headaches and oligomenorrhea seen in this patient. However, her prolactin level is normal, and she has no visual disturbances (e.g., bitemporal hemianopsia), making this study less relevant.

Answer B: The combined oral contraceptive has both estrogen and progesterone, but the doses are higher than those needed for hormone replacement. For this reason, it is generally not considered first-line for the treatment of POI.

Answer D: Increasing this patient’s levothyroxine dose is unnecessary, as her TSH level is within the normal range. Furthermore, while hypothyroidism may cause menstrual irregularities and temperature dysregulation, it is unlikely to cause vaginal dryness and subsequent dyspareunia.

Answer E: Vaginal estradiol gel is an effective method of estrogen replacement in women with POI. However, used alone it may increase the risk of endometrial hyperplasia and cancer, so it should only be used in combination with a systemic progesterone.

Bullet Summary:
Premature ovarian insufficiency should be treated with estrogen and progesterone replacement.