31 HT for Menopause Besinque Flashcards
What is the definition of Menopause?
Cessation of menses. Defined retrospectively after 12 months without menstruation
What is the definition of Perimenopause?
Begins with first signs and symptoms of endocrine change. Menstrual cycle becomes irregular. Ends one year after final menstrual cycle
What are the two key physiological changes in menopause?
Loss of primary ovarian follicles (which produce the main estrogen in the body (Estradiol). Resulting decrease in serum and tissue estradiol levels and higher Estrone levels (estrogen made from the adrenal gland)
What is Natural/Spontaneous menopause?
Final menstrual period (FMP), confirmed after 12 consecutive months of amenorrhea with no obvious pathologic cause
What is Induced Menopause?
Permanent cessation of menstruation after bilateral oophorectomy or iatrogenic ablation of ovarian function. Induced menopause often has worse symptoms than natural
What are the vasomotor menopause-related symptoms?
HA. Palpitations. Night sweats. Insomnia/sleep disturbance
What are the Genitourniary menopause-related symptoms?
Vaginal dryness. Dyspareunia. Vaginal itching/burning. Urinary frequency, dysuria, urgency. Vaginal dryness/itching/burning is due to atrophy of the vagina in the absence of estrogen
What are some other systemic menopause-related symptoms?
Fatigue. Reduced sexual/arousal. Anxiety, irritability and depression. Cognitive difficulties. Backache/stiffness
What medical conditions are more common after menopause?
Osteoporosis. Atherosclerotic disease
What are the types of Estrogens used in HT?
17 beta-estradiol. Conjugated equine estrogens (CEE). Estrone derivatives (including synthetic conjugated estrogens, esterified estrogens, and others (derived from yam, soy or lab))
What are the contraindications for Systemic Estrogen Therapy (ET)?
Pregnancy. VTE. Breast cancer. Estrogen-sensitive cancers. Liver disease. Hypertriglyceridemia)
What are the types of Progesterons used in HT?
Synthetic progestogens. Structually related to progesterone. Structurally related to testosterone
What are the two types of Progestogens?
Progesterone. Progestins
What are Progesterones?
Produced by ovary after ovulation and by placenta during pregnancy
What are Progestins?
Synthetic progestogens. Structurally related to progesterone (MPA). Structurally related to testosterone (norethindrone, norethindrone acetate, norgestrel, levonorgestrel)
What are the Progestogen Indications?
Primary menopause - related indication for progestogen is endometrial protection from systemic ET. Adequate progestogen recommended for women with an intact uterus using systemic ET. Progestogen generally not indicated with local, low-dose ET for vaginal atrophy
What are the possible side effects of Progestogens?
Swelling and breast pain more common with MPA. Acne and hirsutism more common with levonorgestrel and norethinedrone. Dizziness and fatigue associated with high-dose progesterone. Metabolic effects differ
What Progestogens have a higher rate of causing Acne and Hirsutism?
Levonorgestrel and Norethinedrone
What are the FDA-Approved Indications for HT?
Treatment of moderate-to-severe vasomotor symptoms associated with menopause (most estrogens). Treatment of vulvar and vaginal atrophy (most estrogens). Prevention of postmenopausal osteoporosis (some estrogens)
What are the HT options?
ET. EPT. CC-EPT (continuous-combined estrogen-progestogen therapy (daily administratino of both estrogen and progestogen)). CS-EPT (continuous-sequential estrogen-progestogen therapy (estrogen daily, with progestogen added on a set sequence)). Progestogen (encompassing both progesterone and progestin)
How should dosages be in HT?
Therapeutic goal is lowest effect estrogen dose consistent with individual treatment goals, benefits, and risks, plus corresponding low progestogen dose for women with uterus. Lower doses better tolerated, may have more favorable benefit-risk ratio than standard doses (but lower doses have to been tested in long-term trials). Additional local ET may be needed for persistent vaginal symptoms
What is the normal starting dose for Oral Conjugated Estrogen (CE)?
0.3mg (Premarin)
What is the normal starting dose for Oral Micronized 17 beta-Estradiol?
0.5mg
What is the normal starting dose for Transdermal 17 beta-Estradiol patch?
0.014-0.025mg
What is the typical lowest dose of oral medroxyprogesterone acetate (MPA)?
1.5mg
What is the typical lowest dose of oral norethindrone acetate?
0.1mg
What is the typical lowest dose of oral drospirenone?
0.5mg
What is the typical lowest dose of oral micronized progesterone?
50mg
How many days does progestin need to be used to prevent endometrium problems?
At least 10 days/cycle
What kind of Estrogen Therapy is preferred when solely vaginal symptoms?
Local ET
What is required for endometrial protection from unopposed systemic ET?
Systemic Progestogen
What are some estrogen only oral ET therapies?
Premarin (CEE). Estrace (Estradiol)
What are some oral therapies that contain only progestogen?
Prometrium (micronized progesterone). Provera (MPA)
What is in Prempro?
Oral therapy containing both estrogen (CEE) and progestogen (MPA)
What is the only Estrogen Only drug that is FDA approved for women with a uterus with no progestogen in it?
Menostar (Estradiol, low dose)
What are the two transdermal patches that have both estrogen and progestogen?
Climara Pro. CombiPatch
What type of estrogen is found in ALL transdermal patches?
Estradiol
What vaginal cream/gel/tablet contains progestogen only?
Crinone/Prochieve
What vaginal cream/gels/tablet contains estrogen only?
Premarin. Estrace. Vagifem
What vaginal ring contains estrogen only, and released locally?
Estring
What vaginal ring contains estrogen only, and released systemically?
Femring
What vaginal IUD contains progestogen only?
Mirena (Levonorgestrel)
What is the timing of HT initiation like?
Initiation in relation to proximity to menopause seems to have strong impact on long-term health outcomes. Early HT initiation may reduce total mortality and CHD risk
What is the timing of HT initiation like in women > 60 who had natural menopause at median age and never used HT?
Should not start HT without compelling indication/counseling
What is the duration of HT use?
No clear indication that longer HT duration improves or worsens the benefit-risk ratio. HT effects on long-term risks have not been studied in perimenopausal women. Thus, findings of postmenopausal women should be extrapolated with caution for younger women
When is extending HT use acceptable?
For women well aware of potential risks and benefits. With lowest effective dose. For prevention of further osteoporosis-related fracture and bone loss when alternate therapies are inappropriate or benefit-risk ratio is unknown. With clinical supervision
What is symptom recurrence and HT discontinuance like?
50% chance of vasomotor symptoms recurring when HT discontinued. Decision to continue HT must be individualized. Better to taper off
What are the Androgens used?
Estratest. Estratest HS
What is Estratest indicated for?
Vasomotor symptoms if estrogen alone ineffective. Testosterone has also been used to improve sexual function. Not FDA-approved for this use
What are Estrogen Receptor Agonist-Antagonists (formerly SERMS)?
Mediate effects through estrogen receptor binding. Activate certain estrogenic pathways and block others. None currently indicated for menopause-related symptoms. Can cause hot flashes from estrogen receptor blockade
What is compounded “Bio-Identical” HT?
Manufactured synthetically by the conversion of diosgenin extracted from soy and yams.
What is an example of a Bioidentical Hormones?
Prometrium (oral progesterone)
What is Estriol (E3)?
Biologically weak estrogen. Greatest production during pregnancy. Binds weakly to estrogen receptors. Can induce endometrial hyperplasia if dosed adequately. Does not prevent bone loss. Shown to be effective topically in reversing vaginal atrophy
What are some lifestyle alternatives for vasomotor symptoms?
Cooling body core temperature. Exercise. Avoiding hot and spicy foods. Pace respirations. Relaxing activities
What are the benefits of HT?
Vasomotor symptoms. Bone. Mood changes. Sleep quality. Sexual function. Urogenital symptoms. Skin changes
What is the most common symptom of perimenopause?
Hot flushes. Characterized by visibly reddened skin, excessive perspiration, dizziness, HAs, palpitations, and may be associated with chills
What are the risk factors for hot flushes?
African American. Obesity. Estrogen withdrawal. Smoking. Surgical castration. Family history
What is the pathophysiology of hot flashes?
Estrogen levels do not differ between symptomatic and asymptomatic women. Not caused by pulses of luteinizing hormone. Not caused by changes in endogenous opiates. Triggered by small elevations in core body temperature acting within a reduced thermoneutral zone. Elevated brain NE narrows the thermoneutral zone
What is the clinical management of MILD vasomotor symptoms?
Encourage lifestyle changes. Nonprescription remedies (dietary isoflavones, black cohosh, vitamin E)
What are some Non-Hormonal Off-Label prescription therapies for vasomotor symptom relief?
Antidepressants (Venlafaxine, SSRIs). Anti-convulsants (Gabapentin). Anti-hypertensives (Clonidine and methyldopa). Sedatives (Bellergal)
What is the only FDA-approved treatment for moderate to severe vasomotor symptoms?
Systemic HT
How does HT affect osteoporosis?
HT proven to reduce postmenopausal osteoporosis-related fractures. Many systemic ET-containing products approved for prevention of postmenopausal osteoporosis through long-term treatment. Extended use of HT is option for women with low bone mass, regardless of menopause symptoms, when alternate therapies not appropriate or risk-benefit ratio is unknown
What is the etiology and diagnosis of vulvovaginal atrophy?
After menopause, estrogen levels decline progressively. Result: atrophy of vaginal and other estrogen-dependent tissues. Symptoms: dryness, soreness, irritation, and postcoital bleeding
What is the MOA of vulvovaginal atrophy?
Estrogen production reduced. Thinning of epithelial cells. Less exfoliation of vaginal cells. Less glycogen produced from exfoliated cells. Less glucose produced. Less lactic acid produced by action of lactobacilli on glucose. pH increases. Overgrowth of other bacteria
What are some practical considerations for treatment of vaginal atrophy?
Avoid harsh perfumed soaps, detergents, and fabric softeners. Avoid use of soap on inner vulva. Exercise care with warming and mentholated lubricants and moisturizers. Wear cotton underwear
What vaginal rings can be used for vaginal atrophy?
Estring (indicated for atrophy of vagina and lower urinary tract). Femring (indicated for menopausal symptoms and vaginal atrophy)
How do vaginal tablets work for vaginal atrophy?
Estradiol vaginal tablets. Ultra-low dose. Inserted with an applicator or finger. Used daily for 2 weeks and then twice weekly
What are the concerns about safety of HT?
Breast cancer, stroke, heart disease. Women dislike the HT-related vaginal bleeding
What did the Womens Health Initiative (WHI) estrogen + progestin trial find?
Decrease in hip fracture and colorectal cancer. Increase in CHD, stroke, PE, and breast cancer. Trial stopped early, clear harm
What did WHI estrogen-alone and health outcomes show?
Decrease risk of hip fractures, increased risk of stroke. Everything else (CHD, PE, breast cancer, colorectal cancer, total mortality) was null
What are the FDA guidelines for Hormonal Therapy?
Effective for treating vasomotor symptoms and vaginal dryness, preventing osteoporosis. Use topical therapy for vaginal dryness alone. Use as last resort for osteoporosis prevention alone. Use lowest dose and shortest duration possible
What are the side effects from estrogen in HT?
Breast tenderness. Nipple sensitivity. Leg cramps. Vaginal discharge. Fluid retention
What are the side effects from progestin in HT?
Breast pain. Bloating. Increased appetite. Aggression. Anxiety. Depression. Irritability
What is a big reason for women to stop HT?
Uterine bleeding in a major unwanted consequence to HT for many patients
What are the factors in unwanted bleeding in HT?
More likely to induce bleeding when initiated early. Spotting or bleeding may occur during first 3-4 months. Sequential therapy results in withdrawal bleeding. Continuous combined regimens result in no bleeding after 1 year
How can skin irritation be minimized in HT?
Rotate patches. Use oral estrogens. Apply patches to buttocks
How can nausea be minimized in HT?
Take estrogen at bedtime. Lower the estrogen dose. Use patches
How can mood swings, irritability or cyclic depression be minimized in HT?
Lower progestin dose or formulation. Continuous combined regimens or intermittent progestins
What should you tell women about the risks and benefits of HT?
Vasomotor relief. Potential risk of breast cancer, stroke, or VTE. Potential benefits of bone protection and reduction in colon cancer
