Precocious PubertyCollege of Mount Saint Vincent

Carmen Saunders

Nur 652

Precocious Puberty

• Defined as sexual development occurring before age 8 yrs in females and age 9 yrs in males

• Occurs more often in females• It involves not only early physical changes of

puberty, but also linear growth acceleration and acceleration of bone maturation, which leads to early epipheseal fusion and short adult height.

• Two types- 1) central precocious puberty (more common) or GnRH dependent puberty 2) GnRH independent precious puberty ( Ferri, 2009).

Differential Diagnosis

• Most common diagnoses to consider:

• Premature thelarche-breast development without pubic hair growth, without accelerated bone maturation, and with a normal height outcome. No treatment required and resolves spontaneously

• Premature adenarche- involves only pubic hair manifestations with no other manifestations of puberty.No treatment is required however increased incidence with CNS abnormalities

• GnRH dependent- idiopathic, CNS tumors, hypothalamic hamartomas, nuerofibromatosis,hydrocephalus, and CNS infections

• GnRH independent- congenital adrenal hyperplasia, adrenocortical tumors, McCune-Albright syndrome,gonadal tumors, severe hypothyroidism, exposure to exogenous sex steroids ( Dor, 2009).

Workup

• Growth, development, order of appearance of secondary sex characteristics, pubertal development in family members, medications, neurological symptoms, Tanner staging, abdominal and nuero exam

• Breast and genital examination for pubertal development

Laboratory tests

• GnRH testing to determine if dependent or independent cause

• Sex hormone studies: lutenizing hormone, follicle stimulating hormone, hCG, testosterone (males), estrogen (females). Levels of sex steroids should be determined in the morning with use of assays that have detection limits adapted to pediatric values. In girls, serum estradiol levels are highly variable and have a low sensitivity for the diagnosis for precocious puberty.

• T4 thyroid-stimulating hormone

Imaging studies

• CT scan or MRI of the brain or pituitary gland to evaluate for CNS pathology

• Pelvic ultrasound to evaluate for cysts or tumors

• Abdominal imaging with CT scan if intrabdominal pathology is suspected.

• Radiograph of the left wrist to estimate physiologic age with chronological age

Treatment

• Depends on the etiology of the precocious puberty

• GnRH agonists for treatment of gonadotropin dependent precious puberty (leuprorelin, leuprolide, triptorelin, etc)

• For CNS lesions depends on location and type of lesion, and overall prognosis of underlying problem

• For treatment of severe hypothyroidism treatment with thyroid hormone will result in regression of sexual development and the child will undergo puberty later in life

• For familial male gonadotropin independent precocious puberty, the androgen synthesis inhibitor ketoconazole can be used , or a combination of testolactone and spironlactone can be used

Outcome

• For true precocious puberty and some CNS lesions outcome is usually very good

• When drug therapy is instituted, it is continued until a time when further pubertal development is appropriate and then discontinued, allowing the child to progress thorough puberty

• Refer to an endocrinologist for long term treatment as they will need long term management and evaluation

• Emotional needs of the child must be tended to and parents may need referrals to support groups or therapy

Menopause

Carmen Saunders

Nur 652

Menopause

• The occurrence of no menstrual periods for 1 yr after age 40 yrs or permanent cessation of of ovulation after lost ovarian activity

• It is a climacteric reproductive stage of life marked by waxing and waning estrogen levels followed by decreasing ovarian function. Premature ovarian failure and no menstrual periods may also occur because of depletion of ovarian follicles before the age of 40 yrs

• Average age in US is 51• Age at which menopause occurs is genetically determined• Perimenopause starts mid 40s to late 40s • Smokers start menopause 1.5 years earlier than non

smokers (Ferri, 2009)

Types of Menopause

• Natural- absence of menses for 1 year. Occurs between the ages of 45-55

• Induced- bilateral salpingo-oopherectomy(BSO) or chemotherapy

• Premature menopause or premature ovarian failure-natural menopause occurring before age 40. Genetic or autoimmune cause but often no explanation.

• Perimenopausal- transitional state when hormone levels are fluctuating and begin to experience physical changes before the last menstrual cycle.Usually begins in 40s.Characterized by changes in menstrual flow,skipped cycles, and length of cycle changes

• Climacteric-the phase a women makes from reproductive to non-reproductive in her aging process ( Buttaro, 2008).

Physical Findings

• Vasomotor- (hot flashes, day sweats, night sweats)• Insomnia, shorter sleep latency• Irregular bleeding or bleeding that is heavier or

prolonged• Atrophic vaginitis which can cause burning

itching, bleeding, and dyspareunia• Urinary incontinence or urogenital atrophy• Sexual changes- decreased libido• Psychological symptoms-anxiety, depression,

nervousness, irritability, insomnia, difficulty concentrating

Diseases Associated with Postmenopausal women

• Cardiovascular- leading cause of mortality of women in US. 1 in 3 die of CHD whereas 1 in 25 die of breast cancer

• Osteoporosis-low bone mass causing increased risk for fractures

• Mammograms every 1 –2 years• Pap smears 1 –2 years• Cholesterol checks• Blood pressure at least every 2 years• Colorectal screening at age 50 ( Buttaro, 2008).

Etiology of menopause

• Most common is physiologic caused by depleted granulosa and theca cells that fail to react to endogenous gonadotropins, producing less estrogen;decreased negative feedback in the hypothalamic pituitary access, increased FSH and LH which lead to stromal cells that continue to produce androgens as a result of the LH stimulation

• Surgical castration• Family history of early menopause, cigarette

smoking, blindness, Turners syndrome, and precocious puberty ( Ferri, 2009).

Differential Diagnosis

• Hypothalamic dysfunction• Hypothyroidism• Pituitary tumors• Pregnancy• Adrenal abnormalities• Ovarian abnormalities

» Poycystic ovarian syndrome

• Leukemia and other cancer• Poycystic kidney disease• Cardiac abnormality• Ovarian neoplasm• Tuberculosis of the endometrium

Workup

• Height,weight, BP, breast exam, pelvic exam

• Assess risk for cardiovascular disease, osteoporosis, cigarette smoking, hx of breast cancer, liver disease, coagulation disorders

Laboratory test

• FSH/LH/estrogen-menopause when FSH is consistently above 30 and depressed estrogen level

• CBC-anemia• Chemistry profile,fasting lipid,BUN,creatinine• Liver enzymes (esp if considering HT)• TSH- exclude hypothyroidism• Pap smear ,endometrial biopsy, or dilation and

cutterage in patients who have had irregular periods or intermenstrual or postmenopausal bleeding

• hCG pregnancy test

Imaging studies

• Mammogram

• Bone density test

• EKG

• CT scan or MRI of stella of pituitary tumor is expected

Non-pharmacological therapies

• A balanced diet with total fat less than 30% of calories

• Avoid smoking, caffeine, and excessive alcohol intake ( can trigger hot flashes)

• 1500 mg of calcium per day

• Vaginal lubricants to help with the dryness,dypareunia,and atrophy.

Treatment

• Estrogen replacement in symptomatic patients can be done in a variety of forms including oral replacement, patch,creams, and vaginal inserts. The lowest effective dose should be prescribed

• Before estrogen is prescribed a complete history and physical are needed. If a patient has an estrogen dependent malignancy,unexplained abnormal bleeding,history of thrombophlebitis,or acute liver disease estrogen is contraindicated. Smoking is not contraindicated but the patient should be counseled on smoking cessation and try other methods to relive symptoms first.

• In women who have had a hysterectomy it is advised that HT should be initiated with estrogen alone. In women with a uterus progestin is usually added to reduce the risk of endometrial cancer

Hormone Therapy

Titrate dose depending on symptoms• Example:conjugated estrogens:start with 0.3 mg qday and increase to

1.25 depending on symptoms• Estradiol-start with 0.5 mg qday and increase to 2mg qday• If concerned about hepatic function, inflammatory effects ,or

thrombotic effects, a transdermal should be prescribed• Statins should be used concurrently when indicated• Monitor for breast disease, changes in lipid profile, fasting glucose

levels, and unexpected uterine bleeding• Side effects-increased risk of breast cancer,uterine cancer>10 years,

stroke, and venous thromboembolism• Benefit-reduced incidence of osteoporosis

Types of Hormone Therapy

• Cyclic hormone Therapy-estrogen is used for 25 days each month with progestin added the last 10-14 days, followed by 3-6 days of no therapy.80 percent have withdrawal bleeding when the progestin is stopped.Vasomotor symptoms may occur during therapy-free interval

• Continuous-Cyclic Hormone Therapy (Sequential)-estrogen is used continuously each day of the month and progestin is added 10-14 days each month. Uterine bleeding occurs in about 80 percent of women when progestin is withdrawn but no estrogen free period when vasomotor symptoms could occur

• Continuous Combined Hormone Therapy-Estrogen and progestin are taken everyday.80 percent experience no bleeding however when it does it occur it is unpredictable in timing ( Buttaro, 2009).

Treatment

• The 2 most common reasons that women discontinue therapy is fear of cancer and vaginal bleeding.

• Estrogen therapy side effects include breast tenderness, headaches, and nausea

• Progestin side effects include withdrawal bleeding,bloating,mood changes, and rash

• For women whom estrogen is contraindicated or do not want to take estrogen therapy the following regimens can be used:

-antidepressants- Effexor and Paxil

-Dep-Provera 150 mg IM qmonth

-Clonidine 0.05 to 0.15 mg qday

Screening Parameters

• For women using estrogen versus progestin endometrial evaluation should be considered when irregular bleeding persists more than 6 months after beginning therapy,or earlier if other risk factors are present.

• Persistent vaginal bleeding in a postmenopausal woman,whether on or off HT, requires evaluation with and endometrial biopsy or dilation and curettage, despite transvaginal ultrasound findings.

Cardiovascular Disease Prevention

• Smoking cessation• Blood pressure control -goal less than 120/80• Cholesterol management-TC<200,LDL<100,HDL>60

• Weight management-BMI 21-25

• Physical exercise-5 times per week for at least 30 minutes• Limit alcohol to more than 0.5 ounces of ethanol per day• Limit sodium intake to less than 2400mg per day• Reduced intake of saturated fat

Osteoporosis

• Characterized by increased bone fragility and increased susceptibility to fracture

• Also defined as a BMD – 2.5 sd or less below the young normal mean

• Rate of bone resorption exceeds that of bone formation

Risk factors

• Unmodifiable- advanced age, female gender, Caucasian or Asian, hx of fx, dementia, history of fracture in first degree relative

• Modifiable-hypogonadism, cigarette smoking, excessive alcohol use,, low calcium intake, low body weight, inactivity, glucocorticoid use, thyrotoxicosis, recurrent falls,

Diagnostics

• Cbc with diff, serum electrolytes, BUN and creatinine, LFT,serum calcium, serum phosphorus, 25- hydroxyvitamin d,TSH, PTH, 24 hour urine calcium, bone densitometry

• Primary osteoporosis-includes bone loss arising from menopausal estrogen deficiency or aging.

• Secondary results from an acquired or inherited disease that interferes with bone remodeling or increases bone turnover.

Prevention

• Much of the bone loss is irreversible so prevention should be the major focus of health care providers

• Adequate calcium – 1000 –1300 mg of calcium a day and vitamin d 200-600 units daily for adults

• Weight bearing exercise• Avoiding excessive alcohol intake

• Avoid cigarette smoking

Osteoporosis Management

• Estrogens (oral and transdermal) decrease bone loss, reduce the incidence of fracture, and prevent height loss

• Biphosphinates approved for the treatment of postmenopausal osteoporosis are: Aldrendronate (Fosamax), Risedronate ( Actonel), and ibandronate ( Boniva).

• Tamoxifen can promote increased bone density but vasomotor symptoms are common

• Raloxifene (Evista) is a SERM used for prevention and treatment of osteoporosis contraindicated in women who have had a previous thromboembolism

Case Study 1

• A 17 year old adolescent female presents with never having menstrual symptoms but is otherwise in good health. Her older sister and mother both experienced menarche at age 13. She denies any excess eating aversion or excessive exercise. She is 51 inches tall and weighs 103 lbs. Her neck is supple without masses. Her breasts appear to be in Tanner Stage 1 and her pubic pattern also appears to be in Tanner Stage 1.Abdominal exam reveals no masses and external genitalia are normal.The cervix appears normal and on bimanual exam she has a small uterus with no adnexal masses

Answer

• Diagnosis-Delayed Puberty. Most likely gonadal dysgenesis ( Turner syndrome)

• Tests-FSH level to determine CNS problem versus ovarian problem (increased inTurner)Estrogen level(decreased)

• Abdominal ultrasound to visualize ovaries(no true ovaries just bands of fibrous tissue referred to as gonadal streaks

• Giemsa banded karotype to confirm clinical diagnosis

Cardio referral for valvular abnormalities or aortic coarctation

Renal ultrasound

Considerations

• Primary ammenorhea• Breast development should occur by age 14• Lack of estrogen confirmed due to short stature

lack of breast development• Absent pubic and axillary hair consistent with

delayed puberty• Internal and external genitalia will remain normal

but will remain infantile until late in adult life ( Toy, Baker, Ross, & Jennings, 2009).

Treatment

• Estrogen replacement therapy early in adolescence

• Some benefit from recombinant human growth hormone therapy

• Refer to geneticist, endocrinologist, cardiologist

• Refer to Turner syndrome support groups.

Case Study 2

• A 50 year old woman complaints of irregular menses over the past 6 months with symptoms of vaginal dryness, insomnia, hot flashes, and occasional night sweats. Her BP is 126/78 heart rate 96 beats per minute, and temp 99.1. Her thyroid gland is normal to palpation.Breast are symmetric with no masses or discharge. Cardiac and lung exams are unremarkable. Examination of external genitalia does not reveal any masses.

Answer

• Dx-Perimenopausal state-Climacteric• Tests-FSH/LH ( elevated), TSH,chem panel,pap

smear,pelvic US• Differential dx-pregnancy,hypothyroidism,ovarian

abnormalities,hypothalamic dysfunction,adrenal abnormality,polycystic ovarian syndrome

• Treatment-hormone replacement therapy ( always inform of side effects), clonidine,antidepressant, Depo-Provera shot,prevention of osteoporosis, and prevention of cardiac complications

Case Study 3

• A 57 year old woman has an intact uterus,no symptoms, and is in the office for routine care. She is a smoker, has not had a period in 10 years and is otherwise healthy with no complaints. She is 5’6” and weighs 130 lbs. She has never received HRT and has never received any counseling about it

Assessment

• Patient’s height has decreased in the last 2 years. She is 1 inch shorter than her maximum. When asked about sexuality she reports dyspareunia and vaginal dryness;she is not happy with these symptoms. Her mother had a wrist fracture with a minor fall at age 65. The patient is taking a multivitamin and some herbal remedies. She has cut back to 3 cups of coffee a day. In discussing her own beliefs, she expresses fear of breast cancer with the use if HRT

Management

• What is she at risk for-osteoporosis (family history,loss of height, and smoking).

• Considerations - ask about DVT in the past, since she is a smoker she is more at risk for thromboembolism.Pt should be counseled on smoking cessation but smoking is not totally contraindicated in HRT

• Tests-BMD >2.5 = osteoporosis,biochemical profile to evaluate renal and hepatic function, primary hypothyroidism, and malnutrition, CBC-blood count and nutritional status,TSH-hyperthyroidism,24 hour urine collection for calcium, biochemical markers for bone remodeling

• Treatment-HRT(estrogen or progestin) if patient has agreed to smoking cessation,biphosphinates ( alendronate or risedronate),vitamin d (400 u per day) calcium supplement(1500mg per day)

References

• Bramswig, J. & Dubbers, A. ( 2009). Disorders of pubertal development. Duetsches Arzteblatt Intenational, 106 (17), 295-304.

• Buttaro, T., Tyrybulski, J., Bailey, P., & Sandberg-Cook, J. (2008). Primary care: A collaborative practice, 3rd Ed. St. Louis, MO:Mosby-Elsevier.

• Dor, K., & O’ Connell, T. (2009). Instant workups: A clinical guide to obstetric and gyneological care. Philadelphia, PA: Saunders, Elsevier.

• Ferri, Fred (2009). Clinical Adviser. Philadelphia , PA:Mosby Elsevier.

References

• Toy, E., Baker, B., Ross, P., & Jennings, J.

( 2009). Case files: Obstetrics & gynecology. Mc-Graw Hill Companies.