Premature Ovarian Failure

Hypergonadotropic ovarian failure occurring prior to age 40

Premature Ovarian Failure

Defects in X chromosome with gonadal dysgenesis Mutations in FSH

Premature Ovarian Failure

Galactosemia 17--hydroxylase deficiency

Premature Ovarian Failure

Autoimmune polyendocrinopathies like autoimmune polyendocrinopathy/ca ndidiasis/ectodermal dystrophy (APECED) Thymic hypoplasia

Premature Ovarian Failure

abnormalities in the structure of gonadotropins, in their receptors, or in receptor binding could be associated with POF

Premature Ovarian Failure

Ionizing radiation
400-500 rads = 50% ovarian failure 800 rads = failure in all women

Chemotherapy
cyclophosphamide

Ovarian surgery Viral infections

mumps

Premature Ovarian Failure

POF causes otherwise specified

Premature Ovarian Failure: Management

Screening for autoimmune disorders and kayotyping Vaginal ultrasound
Assess size of ovaries Degree of follicular development

Premature Ovarian Failure: Management

Estrogen replacement Oocyte donation
For fertility Ovarian stimulation usually unsuccessful

EFFECTS OF MENOPAUSE ON VARIOUS ORGAN SYSTEMS

Central Nervous System

Brain = active site for estrogen action and formation Mediated by ER and

Central Nervous System

Central Nervous System

Hot flush
Pathognomonic symptom of menopause; vasomotor episode Hallmark feature of declining estrogen status in the brain Each episode lasts about 3-4 minutes and occurs unpredictable, irregular intervals Increased digital perfusion and increased vascular peripheral skin temperature and sweating

Central Nervous System

Hot flush
Usually occur for 2 years after the onset of estrogen deficiency Can persist for 10 years May cause sleep disruption May be improved with estrogen therapy

Central Nervous System

Cognitive decline
Aging + estrogen deficiency

Collagen
Important component of bone and skin Serves as major support tissue for the structure of pelvis and urinary system Implicated in post menopausal symptoms including prolapse and urinary symptoms

Collagen
Estrogen therapy:
Improves collagen content Improves skin thickness substantially after about 2 years of treatment

Genital Atrophy
Vulvovaginal complaints often associated with estrogen deficiency
Thin, paler vaginal mucosa Moisture content is low pH increases >5 Mucosa exhibit inflammation and small petechiae

Bone Loss
Role of estrogen
Estrogen suppress bone turnover and maintain certain rate of bone formation Decreases osteoclasts by increasing apoptosis

Estrogen deficiency
increases the activities of remodeling unit prolongs resorption shortens the phase of bone formation.

Trabecular bone > cortical bone

Leads to osteoporosis

Bone Loss
Detected by a variety of radiographic methods Dual energy X-ray absorptiometry (DEXA)
Standard of case for detection of osteopenia and osteoporosis Osteopenia: T-score -1 to -2.5 SD Osteoporosis: >2.5 SD

Bone Loss

Bone Loss: Treatment

Estrogen
Reduce the risk of osteoporosis Reduce osteoporotic fractures

Selective estrogen receptor modulators (SERMs)

Raloxifene, droloxifene, tamoxifen Decrease bone resorption

Tibolone
Mixed estrogenic, antiestrogenic, androgenic and progestogenic properties Effective for treatment and prevention of osteoporosis

Bone Loss: Treatment

Biphosphonates
Etidronate, Alendronate, Risedronate, Ibandronate Incorporation with hydroxyapatite increases bone mass Reduce both spine and hip fractures For treatment and prevention

Calcitonin
Inhibit resorption Decrease vertebral fractures

Bone Loss: Treatment

Fluoride
Increases bone density Prevents vertebral fractures

Intermittent PTH
Teriparatide 20 ug (SC) in <18 mo Increase bone mass and bone density Reserved for severe osteoporosis

Bone Loss: Treatment

Adjuncts
Vitamin D Calcium Exercise

Cardiovascular
Accelerated rise in total cholesterol
Increase in LDL-C Decrease in HDL-C

Increase insulin resistance

Cancer Risks in Postmenopausal Women (Using HT and ET)

Endometrial CA
2x-8x higher than in general population Risk is far less compared to EM hyperplasia Lower risk for HT

Cancer Risks in Postmenopausal Women (Using HT and ET)

Breast Cancer
2xrisk increases after 5 years of HT Progestogen: major contribution to the risk
Increases breast mitotic activity

Family history and genetic mutations increases risk

Cancer Risks in Postmenopausal Women (Using HT and ET)

Ovarian Cancer
Increased risk with long term use of ET and HT Although recent analysis found no association

Cancer Risks in Postmenopausal Women (Using HT and ET)

Colorectal Cancer
third most frequent cancer in women and is often preventable by the detection and treatment of polyps Women >50 yo should have colorectal evaluation Data have been fairly consistent for a reduction in risk with the use of HT/ET