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dysfunctional uterine bleeding, secondary amenorrhea, preventing endometrial hyperplasia

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Indications for progesterones

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metastatic cancer, combination with estrogen for vasomotor symptom management

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Indications for androgens

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hypogonadism in men

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Indications for androgen therapy in men

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relief of moderate to severe vasomotor symptoms in postmenopause, relief of vulvovaginal atrophy in postmenopause, osteoporosis prevention in postmenopause, dysfunctional uterine bleeding, secondary amenorrhea, primary ovarian failure and/or premature oophorectomy, prostate cancer in palliative treatment, and certain breast cancers in palliative treatment

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Indications of hormone therapy (HT) for women

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diminished libido in menopause

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Unlabeled uses of hormone replacement therapy

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perimenopause, menopause, and postmenopause

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Three distinct stages in menopausal transition

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8-10 years prior to menopause; during which symptoms of changes in levels of estrogen and progesterone occur; usually occurs between the ages of 42-55; frequency of ovulation decreases, hot flashes occur, PMS symptoms intensify, irregular menstrual bleeding occurs, unplanned pregnancy is a risk due to irregular ovulation

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Perimenopause

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point in time that occurs after the natural cessation of menses for 12 consecutive months; average age is 51

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Menopause

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5 year period following menopause; commonly associated with hot flashes, sleep interruptions, and vulvovaginal changes

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Postmenopause

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can cause hot flashes during perimenopause and postmenopause; hot flashes can last from 1-4 minutes; associated with the surge in LH and decline estrogen and progesterone levels; can be triggered by emotional stress, excitement, fear, anxiety, alcohol, caffeine, or environmental temperatures; hot flashes occurring at night are called night sweats

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Vasomotor tone instability

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starts early and persists throughout postmenopause causing dryness, dyspareunia, and increased vaginal pH; vaginal pH increased from about 5.0 to 7.0 making the tissue more susceptible to infection; muscle tone decreases throughout pelvic area which leads to urinary tract infections and incontinence; time for lubrication is increased and vaginal secretions decrease; predisposes to urinary tract infections, prolapse, dyspareunia, vaginitis, irritation, bleeding, burning, pruritus, and urinary symptoms such as frequency, urgency, and dysuria

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Vaginal atrophy

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women develop atherosclerosis immediately following menopause within 5-10 years

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cardiovascular

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stimulates enzyme production that affects cholesterol metabolism; breaks down LDL cholesterol and production of HDL cholesterol; also plays a role in maintaining vascular elasticity

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estrogen

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loss of bone mass with postmenopause; can lead to osteopenia and osteoporosis that predisposes women to fractures

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Bone density

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estrogen and progesterone have biochemical, neurophysiological, and structural effects on the brain; estrogen affects cognitive function and memory; estrogen and progesterone aid the thermoregulatory center in maintaining normal body temperature

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brain

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dry skin, fatigue, insomnia, paresthesias, poor sleep quality, increased sleep latency, constipation, mood changes, muscle and joint pain

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Other symptoms caused by menopause

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based on symptom patterns, menstrual changes, and age

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Diagnosing menopause

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conjugated, synthetic, and bioidentical

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three classes of estrogen formulations

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stimulate hepatic globulins and the renin-angiotensin system

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Conjugated and synthetic estrogen

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metabolized into estrone in the liver

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oral estrogen

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creams, gels, patches, and sprays; do not undergo liver first-pass effect and can be dosed at lower levels

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transdermal estrogen

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include bioidentically manufactured progesterone, synthesized manufactured progestogens, and synthesized compounded progestogens; lipophilic and bind to progesterone receptors throughout the body

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Progestogens

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have androgenic properties and others have anabolic characteristics

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Androgens

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used for the treatment of patients with conditions that are hormonal in nature; ex: Methyltestosterone

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Highly androgenic properties

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used to promote weight gain, increase muscle mass, or stimulate red blood cell production in certain forms of anemia

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Androgens with anabolic characteristics

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estrogen effectively treats hot flashes; progesterone can also manage hot flashes but are not commonly used for hot flashes alone due to its side effects

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Vasomotor effects

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oral, vaginal, and transdermal estrogen decrease atrophic vaginitis

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Vaginal atrophy effects

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higher risk of CHD, stroke, and PE in women taking progestogen and estrogen; CHD not found to be increased in estrogen only treatment

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Cardiovascular effects

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estrogen and progestogen effects are breast cancer is controversial; both may increase the risk of breast cancer

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Breast Cancer effects

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hormone therapy slows or stops progression of bone lose and osteoporosis; decreases risk of osteoporosis related fractures by maintaining mineral density

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Bone density effects

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effects of hormonal therapy on brain function is also controversial, some studies show decrease in Alzheimer's incidence and others show an increase in probably dementia

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Brain effects

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unopposed estrogen in postmenopausal women increases the risk of endometrial hyperplasia and cancer; progestogens change the endometrium from a constant proliferative state to secretory thus preventing endometrial hyperplasia caused by estrogen

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Endometrial cancer effects

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hormone therapy predisposes to cholecystitis; decreases the risk of developing colorectal cancer

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GI effects

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relieves symptoms of postmenopause, prevents osteoporosis, and provides quality of life for women experiencing moderate to severe symptoms, may also reduce the risk of colon cancer

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Benefits of hormone therapy

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increases risk of cholecystitis, increase risk for breast cancer, stroke, and CHD

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Downfall of hormone therapy

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-pregnancy is possible during perimenopause; women must be counseled on appropriate contraception -beginning of lifestyle modifications can help manage menopause symptoms -HT use must be individualized; decision to use contraception should be a partnership decision with consideration given to other risks and benefits, quality of life, personal and family history, and personal preference -HT should be started at lowest dose and for shortest time if possible -regularly reevaluate HT need -Progesterone needed for all women with intact uterus; progesterone also used for prevention of endometrial hyperplasia and cancer in postmenopausal women

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Cardinal points of treatment:

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-first step management is lifestyle modifications; -dietary changes include avoiding caffeine, refined sugars, and alcohol; -other dietary changes are decreasing fats, cholesterol, and salts and increasing fiber, calcium, and fluids -Exercise is important for moderating vasomotor symptoms, maintaining cardiovascular health, and promoting general well being; weight bearing and resistance exercises promote bone strength and prevent osteoporosis; walking and upper body weight work are recommended as safe and effective exercise regimen; post menopausal women with no health contraindications should engage in at least 30 minutes of aerobic exercise daily -complementary and alternative therapies are not regulated by the FDA -Herbal and OTC products can interact with prescription medications and each other, thus information on use must be documented

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NONPHARM TREATMENT

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can effectively reduce vasomotor symptoms in postmenopausal women

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SSRI and SNRIs

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have shown to have some efficacy in vasomotor symptoms relief

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Clonidine and gabapentin

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frequently used for breast cancer treatment

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Tamoxifen

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used for osteoporosis prevention and treatment and invasive breast cancer risk reduction

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Raloxifene

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not FDA approved for perimenopause symptom management except irregular menstrual bleeding; provider and patient should make a decision together about the best treatment plan and periodic reevaluations of medications should be done has a woman transitions to menopause

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oral contraceptives during perimenopause

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can be prescribed during perimenopause to reduce symptoms, provide contraception, and reduce abnormal menstrual bleeding; estrogen levels in low dose OCs is 4 times greater than standard HT thus not effective for contraception in perimenopause; low dose OCs contraindicated in smokers due to increase risk of cardiovascular disease and VTE

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Low-dose OCs

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HT should be started in women at low risk of CHD and breast cancer who are experiencing significant menopause-related symptoms; HT used in short term for these symptoms; should be reevaluated annually and tapered as tolerated

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Short-term HT use

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HT not effective in treating symptoms and preventing osteoporosis; risk associated with HT in women who are many years past menopause is aggravating silent heart disease; estrogen should be used only with caution in women with cardiovascular disease, HTN, diabetes, or hyperlipidemia

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Long-term HT use

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include both estrogen and progestogen and are used for women who have their uterus

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Estrogen-progestogen treatment

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used for women who do not have a uterus

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Estrogen-only daily regimen

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initiate at low dose; patient must be taught that full symptoms relief until 6 weeks of therapy; vaginal treatment can be started daily and symptoms relief can be noted within 1-2 weeks

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Oral HT dosage

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recheck patients every 3 months if on oral therapy; evaluate level of symptom control and titrate dose as needed; if symptoms continue increase the estrogen to next higher dose; change estrogen or progestogen if side effects are intolerable and reevaluate after 3 months; annual reevaluation is recommended after stable treatment is obtained; local vaginal products should be evaluated 2 weeks after initiation and titrated as needed

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Adjusting dose

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androgens are classified as Schedule III due to misuse by athletes and others who wish to enhance muscle mass; combination therapy estrogen/androgen is not Schedule III and can be prescribed for menopause-related symptom managements

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Adding androgens to hormone replacement therapy

question

-review bleeding patterns at each visit -schedule yearly physical exams once the dose is stable -regular, age-appropriate screening tests are important (yearly mammograms, pap smears every 1-3 years depending on history, STIs checks, lipid panel and thyroid panel -In androgen therapy, monitor hepatic function and cholesterol; periodic evaluation of h&h, and blood chemistries

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MONITORING

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early studies favor starting HT within 7 years of menopause and using it short term symptom relief only; newer studies favor HT starting within a few years of menopause and low dose should be used to control symptoms for short periods; midlife woman can benefit from estrogen for bladder and urethra and maintain bone strength

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PATIENT VARIABLES-geriatrics

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no indicated in children

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PATIENT VARIABLES-pediatrics

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category x; contraindicated

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PATIENT VARIABLES- pregnancy and lactation

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no race effects reported; except for in prostate cancer, estrogen and progestogen remain female gender specific

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PATIENT VARIABLES-race/gender

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-discuss risk versus benefits and obtain informed consent -advise that HT may take up to 6 weeks to reach full efficacy -review side effects that may occur initially and explain that some will wane over time -take oral HT with food or at bedtime if nausea is a problem -reports any signs of thromboembolic evens or abrupt headaches patterns -routine monitoring is important -monthly self breast exams & yearly mammograms -if on androgen therapy, patient should be counseled on potential virilizing effects

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PATIENT EDUCATION

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lack of testosterone production by the testes due to either disease of the testes itself or disease to the hypothalamic pituitary and testicular axis; severe and produces male infertility

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male hypogonadism

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associated with low testosterone levels, impaired spermatogenesis, and elevated gonadotropins (LH and FSH)

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Primary hypogonadism (congenital or acquired):

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associated with low testosterone levels, impaired spermatogenesis, and low or low/normal gonadotropins

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Secondary hypogonadism

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230-350 ng/dl

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Normal serum testosterone levels

question

used to replace missing hormone; has potential to also disrupt the hypothalamic-pituitary-gonadal axis in a way to shut down sperm production

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MOA-exogenous testosterone hormone

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-confirm diagnosis by symptoms and lab test -establish baseline testosterone, hct, prostate-specific antigens, and prolactin -therapy is individualized increase blood testosterone levels to normal range and avoid supraphysiologic peaks

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Treatment principles for hypogonadism:

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-lifelong treatment is required -patients must understand risk and benefits -patients can help choose medication delivery -consistent treatment at the same time daily is helpful -precautions should be taken to avoid spreading topical testosterone to others -patient must understand the potential for impaired spermatogenesis and possible impaired fertility or infertility -low testosterone levels are associated with prostate cancer

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CARDINAL POINTS OF TREATMENT

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increase exercise and establish good dietary habits

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NONPHARM TREATMENT for hypogonadism

question

When testosterone therapy is instituted, aim for mid-normal testosterone levels with any approved formulations, selected on patient's preference and considering pharmacokinetics, treatment burden, and cost

answer

PHARM TREATMENT for hypogonadism

question

-asses symptoms and adverse effects quarterly after testosterone initiation -measure HCT as baseline, q3months, and annually; HCT greater than 45%=stop therapy -digital rectal exam and PSA within 3 months of starting therapy -measure bone mineral density of lumbar spine and/or femoral neck after 1-2 years of therapy -testosterone supplementation does not boost erectile dysfunction drug response

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MONITORING with hypogonadism treatment

question

monitor HCT levels; careful to do digital rectal exam and PSA testing in elderly patients with history of BPH or family history of prostate cancer

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PATIENT VARIABLES-hypogonadism in geriatrics

question

-exogenous testosterone can impair spermatogenesis and prevent or reduce the potential for fertility -wash hands after applying gel or spray; allow skin to fully dry then always wear a shirt over area that medication is applied

answer

PATIENT EDUCATION for hypogonadism treatment

Chapter 55-Hormone Replacement Therapy – Flashcards

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