Exam 3 Menopause

How do you maintain the most bone density in before menopause?

"Early commencement of prophylaxis after cessation of ovarian function will maintain the highest bone density. Initiation of HT well after the menopause will stop bone loss, but will not return bone density to that which was present at the time of the menopause."

Estrogen, a steroid hormone, is derived from the androgenic precursors androstenedione and testosterone by means of aromatization. In order of potency these estrogens go like?

1. 17 (beta)-estradiol (E2), 2. estrone (E1), 3. estriol (E3). The synthesis and actions of these estrogens are complex. In brief, these forms of estrogen can be summarized as follows: Estradiol - Primarily produced by theca and granulosa cells of the ovary; it is the predominant form of estrogen found in premenopausal women Estrone - Formed from estradiol in a reversible reaction; this is the predominant form of circulating estrogen after menopause Estriol - The estrogen the placenta secretes during pregnancy; in addition, it is the peripheral metabolite of estradiol and estrone; it is not secreted by the ovary

Contraindications for HRT inlude

1. UNDIAGNOSED ABNORMAL VAGINAL BLEEDING 2. KNOWN, SUSPECTED OR HX OF BREAST CANCER 3. ACTIVE DVT, PE OR HX OF THESE CONDITIONS 4. ARTERIAL THROMBOEMBOLIC DISEASE (MI, STROKE) 5. LIVER DYSFUNCTION AND DISEASE 6. ENDOMETRIAL CANCER

*Graph of women ages below 45 and over 45 and hormones they go through?*

25-35

HRT Complications of thrombotic disease and stroke?

Affects synthesis of coagulation factors via liver Use of Transdermal estrogens is probably associated with ↓risk ↑risk noted in both EPT and estrogen-alone arm

Clinical Conditions Associated with Menopause include?

Atrophic Vaginitis Hot Flushes Osteoporosis Sexual Dysfunction

What happens to the urinary tract in menopause?

Atrophic changes Bladder - Atrophic cystitis Urethra - Urethral Caruncle formation Recurrent UTI's

What happens to the Reproductive tract in menopause?

Atrophic changes vaginal epithelium- can lead to Atrophic vaginitis Cervix - can lead to Dyspareunia Uterine - beneficial for those with endometriosis and uterine myomas (become asymptomatic) Ovarian - small size if an ovary is palpated on an exam you must have a high degree of suspicion and ovarian neoplasm must be considered.

When does menopause occur? And what May cause it to come early?

Average age 50-51 years No relationship between menarche and age of menopause Marriage, childbearing, height, weight, and prolonged use of oral contraceptives do not influence age of menopause. *Smoking is associated with early menopause.*

How would a patient describe a hot flash?

Begin with a sensation of pressure in the head, much like a headache. Progresses in intensity until the physiologic flush occurs. characterized as a feeling of heat or burning in the face, neck, and chest, Followed immediately by an outbreak of sweating Affects the entire body Particularly prominent over the head, neck, upper chest, and back. Palpitations may also be experienced. Less common symptoms include: Weakness, Fatigue, Faintness, Vertigo

What is a Urethral Caruncle?

Benign fleshy outgrowth at the urethral meatus. Loss of urethral tone, with pouting of the meatus and thinning of the epithelium, favors the formation of a urethral caruncle with resultant: dysuria, meatal tenderness, and occasionally hematuria.

Pathogenesis for osteoporosis?

Bone loss occurs because bone resorption is excessive, bone formation is decreased, peak bone mass is low, or a combination of all 3 factors. Ovarian estrogen and estrogen administered postmenopausally are protective against osteoporosis. The exact mechanisms by which estrogen regulates bone remodeling are incompletely understood. Estrogens likely modulate osteoclast and osteoblast function possibly via: Effects on cytokines Effects on growth factors transforming growth factor-β tumor necrosis factor-α (TNF-α).

How is osteoporosis treated?

Calcium = Minimum 1200 mg Vitamin D (800-1000 IU/d) Smoking cessation Avoid alcohol Weight bearing and muscle strengthening exercise Bisphosphonates Calcitonin (peptide hormone) Estrogen Used to be the mainstay of therapy for prevention and treatment of postmenopausal osteoporosis. However, health risks > benefits. Parathyroid hormone

How do you diagnose and treat atrophic vaginitis?

Diagnosis based on patient symptomatology and physical exam Treatment water -soluble lubricants Vaginal estrogen preparations preferred (vs. systemic combo's)

What are the 2 stages of perimenopause?

EARLY - (-2)

Osteoporosis guidelines for HRT are what?

ET for osteoporosis prevention is generally reserved for those women who are otherwise using estrogen for menopausal symptoms and/or who cannot tolerate other antiresorptive therapies. There are several options available for use of EHT or EPT for prevention of osteoporosis ORAL OLDER HIGHER DOSING 0.625 mg of conjugated equine estrogens, LOWER DOSING ALSO PREVENTS BONE LOSS, NOT AS WELL AS HIGHER DOSES! 0.3 mg of conjugated equine estrogens, & 0.5 mg of micronized estradioL TRANSDERMAL 0.05 mg of transdermal estradiol, and 1 mg of micronized estradiol, & 0.025-mg transdermal patches low-dose(0.014 mg/d) estradiol approved for prevention of osteoporosis. *** With the tablets, rings, and lowest dose creams, endometrial proliferation is RARE.***

Hormone Replacement Therapy complications?

Endometrial cancer Breast Cancer Thromboembolic Disease Stroke Uterine Bleeding Gallbladder Disease Lipid Metabolism

HRT complications for Lipid metabolism?

Estrogen replacement also has an impact on circulating lipids. many of these effects are favorable. ↑ HDL ↓ LDL

HRT complications for gallbladder disease?

Estrogens cause increased amounts of cholesterol to collect in bile. Leading to increased synthesis of cholesterol. Bile normally has a 75-90% cholesterol, small increases = stone formation. ¾ gallstones are composed predominantly of cholesterol.

Pathogenesis of hot flushes?

Exact mechanism is unknown Some evidence it is a result of a central thermoregulatory function defect. CNS concentrations of norepinephrine and serotonin likely play an important role. Serotonin is also thought to be important in thermoregulation

*graph of the reproductive cycle staging*

Few years riot and one year after.

ONLY GENERAL GUIDELINES CAN BE OFFERED b/c risks and benefits must be evaluated for each patient. Indications for HRT use is what?

Hot Flushes Atrophic Vaginitis MODERATE TO SEVERE hot flashes and Atrophic Vaginitis: - therapy may be used for the shortest duration possible; minimal or no symptoms may not require hormones. Prevention of Osteoporosis ET for osteoporosis prevention is generally reserved for those women who are otherwise using estrogen for menopausal symptoms and/or who cannot tolerate other antiresorptive therapies.

What is the most COMMON and characteristic symptom of peri-menopause?

Hot Flushes Present in 75% of women 82% have the symptom > 1 year 25-50% complain of the symptom > 5 years Length varies from 1-10 minutes Average length of 4 minutes Frequency varies from 1-2/hour to 1-2/week. In women with severe flushes, the mean frequency is 54 minutes

In women taking estrogen only, the incidence of endometrial hyperplasia can be as high as 25% after only 12 months of therapy. What is seen and what is done in this case?

Hyperplasia occurs in women who do not experience vaginal bleeding, bleed only during the medication-free interval, or bleed during drug administration. *** pretreatment biopsy and yearly endometrial biopsies are necessary in all women receiving estrogens alone to assess for the presence of hyperplasia***

HRT RECAP risks

Increase risk of ovarian cancer Increase risk of endometrial cancer Increase risk of breast cancer Increased risk of gallstones Vasomotor sx may worsen after stopping estrogen therapy mortality due to lung cancer long-term hormone replacement therapy increases risk of Cardiovascular disease: coronary events, venous thromboembolism, stroke,

What causes negative feedback on FSH. What does this mean.

Inhibin - hormone synthesized and secreted by the ovarian oocyte. As oocyte number decreases, inhibin levels fall, resulting in a rise in FSH levels (diagnostic marker of menopause). Follicular atresia results in declining estrogen and inhibin The irregular episodes of vaginal bleeding in premenopausal women represent the irregular maturation of ovarian follicles with or without hormonal evidence of ovulation.

LATE - (-1) perimenopause stage

Interval of amenorrhea of > 60 days Characterized by increased variability in cycle length. FSH is usually > 25 IU/L Most women begin to experience symptoms including vasomotor symptoms Sleep disturbances Duration typically 1-3 years

What is the treatment for sexual dysfunction?

Local Estrogen cream (preferred vs. systemic) Testosterone - modest improvement in libido

What are symptoms of menopause and helpful to establish it?

May be associated with vasomotor symptoms, sleep disturbance, and vaginal/urinary symptoms Estradiol <20 pg/mL and follicle-stimulation hormone level 21-100 mU/mL helpful in establishing the diagnosis

Early - (-2) perimenopause stage

Menstrual cycles remains regular Cycle length changes by 7 days or more (i.e. length is now 24 days vs. 31)

Before discussing the management of estrogen replacement, it is necessary to review the complications of and contraindications to this type of therapy. Complications and Contraindications play an important role in the ultimate decision regarding treatment for all patients. Complications included in Endometrial cancer?

Most highly charged issue with HRT Estrogen stimulation of endometrium unopposed by progesterone, causes ENDOMETRIAL PROLIFERATION, HYPERPLASIA, and NEOPLASIA. 2- to 8-fold risk ratios ***it is recommended that a progestogen be added to ET to reduce the risk of endometrial hyperplasia or carcinoma *** THERE IS INCREASING RISK OF PROGESTOGENS RELATED TO BREAST CANCER IN HRT PTS.

Synthetic ESTROGEN

Most widely prescribed for years — estrogens like Premarin and progestins like Provera, as well as low-dose OCP's Synthetics refer to man-made hormones — hormones that are made from chemical sources that approximate the hormones the human body makes. Also refers to Premarin, although made from a natural source (horse urine), aren't the same as endogenous estrogens Many synthetic estrogens are stronger than human estrogen Supporters of bio-identical hormones argue that this may cause your liver to work harder than with the bio-identical estrogens. This claim has not been proven by the currently available science. *** Most widely studied form of estrogen

Every woman with menopausal symptoms deserve explanation of what she is experiencing to dispel fear, and to address her symptoms, and reassurance. Such as what?

No rx required = ovarian function is maintaining some uterine bleeding. -If having hot flushes with ovarian function low dose OCP's can be rx'd.

Can Menopause be Prevented?

Nothing can prevent menopause(ovarian function cannot be prolonged indefinitely), nothing can be done to postpone its onset or slow its progress. However, artificial menopause can often be prevented. When ionizing radiation is used for treatment of intra-abdominal disease, incidental ablation of ovarian function often cannot be avoided. In such cases, if an operation will serve equally well to treat the disease, it should be used in preference in order to preserve the ovaries.

HRT complications and Contraindications for uterine bleeding?

Occurs in the majority of patients given estrogen/progestin combos ↑ bleeding Can occur during treatment-free interval (scheduled bleeding) Can occur during medication administration (Unscheduled bleeding). Hyperplastic endometrium is a serious side effect. In women using a combined continuous regimen of estrogen and progestin, bleeding is common in the first several months, does not indicate serious pathology. If the bleeding is heavy or prolonged, = biopsy **If endometrial hyperplasia is present, EPC medications d/c'd, or ↑ progestin dose, or add progestin daily. a repeat biopsy should be performed to check for continuing endometrial hyperplasia

what is physiologic menopause?

Oocytes responsive to gonadotropins (LH, FSH) disappear from the ovary The few remaining oocytes stop responding to the Gonadotropins (LH, FSH) Can be hastened by: Severe infections tumor of reproductive tract Excessive exposure to ionizing radiation Chemo-therapeutic drugs Surgical procedures impairing ovarian blood supply Endocrine or chromosomal abnormalities

What are guidlines for managing HRT?

Osteoporosis Hot flashes Atrophic Vaginitis 4. Progestogen-Estrogen Therapy

Artificial Menopause

Permanent cessation Surgical removal of ovaries When laparotomy is performed for intra-abdominal or pelvic disease (hysterectomy for leiomyomata) Elective bilateral oophorectomy (prevention of ovarian cancer) Radiation therapy Irradiation to ablate ovarian function SE of intra-abdominal disease (damaged by infection or neoplasia)

Two types of menopause:

Physiologic menopasue artificial menopause

The primary disadvantages of bioidentical hormone therapy

Preparations have not undergone rigorous clinical testing for safety or efficacy They are not regulated by the FDA. Safety questions, Quality assurance The purity, potency, and quality of the products is not standard labeling does not need to include the warning the FDA now requires for traditional hormone therapy.

What are Treatments for hot flushes?

Progestins - Second line treatment Avoid in patients with breast disease Clonidine SSRI's and SNRI's - Second Line Treatment Black Cohosh (herbal) - modest effects (concern with stimulation of breast and uterine tissues) Gabapentin - decreases hot flashes by 50-80% (comparable to estrogen in studies!). However sedation is a major side effect limiting its use. Tibolone (synthetic steroid)

A serious outcome of ERT is occurrence of endometrial hyperplasia or cancer. How is this combated?

Progestogens oppose the action of estrogen on the endometrium. Significant reduction of the occurrence of endometrial cancer with estrogen plus progestogen compared with estrogen alone. high-dose estrogens (1.25 mg or greater of CEEs) = 32% hyperplasia, low doses estrogens (0.625 mg or less) stimulated 16% hyperplasias estrogen plus progestins, the occurrence of hyperplasia was 6% , In comparing length, progestogen therapy reduced the occurrence of hyperplasia to: 7 days = 4%, 10 days = 2%, 12 days eliminated hyperplasia.

HRT RECAP Benefits

Reduce sexual dysfunction Improve sleep problems Improve hot flushes and night sweats Reduce aching joints/muscles Improve vaginal dryness Prevents bone loss and osteoporotic fractures HRT may reduce colorectal cancer risk other potential benefits possible reduction in total mortality in women < 60 years old may reduce risk of diabetes may reduce risk of osteoarthritis may reduce risk of cataracts

3 menopause physical changes?

Reproductive Tract Urinary Tract Regression of breast size

HRT Complications of breast cancer?

Risk Factors Early age menarch Older age at menopause Protective Factor Early oophorectomy Many studies have been published since 1974 re HRT and breast cancer. Results vary. The recent prospective, randomized WHI trial estrogen/progestin arm - ↑ risk of invasive breast cancer estrogen-alone arm - breast cancer risk was not increased Long-term use (4-10 years) = ↑risk Addition of Progesetin may actually ↑ risk Risk does not vary dependent on family hx of breast cancer or benign breast dz.

United States Preventive Services Task Force (USPSTF) recommendations for HRT?

Routine use of combined estrogen and progestin not recommended for prevention of chronic conditions in postmenopausal women (USPSTF Grade D) Routine use of estrogen alone not recommended for prevention of chronic conditions in postmenopausal women who have had a hysterectomy (USPSTF Grade D) Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman

What pathogenesis causes atrophic vaginitis?

Smooth, shiny, pale epithelial surface due to increasingly sparse capillary bed. ↑in vaginal PH due to reduced glycogen in the vaginal epithelium ↑bacterial invasion due to disappearance of lactobacilli.

Estrogen HRT Therapy - Indications

Some findings suggest estrogens prevent many common conditions of aging, such as: Alzheimer's disease and Congestive Heart Disease. Estrogen therapy has only been proven to be effective in: The prevention of osteoporosis, Treatment of vasomotor symptoms Treatment of vulvovaginal atrophy

Premature Menopause/Premature Ovarian Failure

Spontaneous amenorrhea before age 40 Prevalence - 0.9% Cessation of menstruation and the development of climacteric (period of decrease of reproductive capacity in women, culminating in menopause) symptoms (hot flushes) and complaints can occur as early as a few years after menarche. *Etiology is unknown. FSH >30 mlU/ml*

Hot Flushes guidelines for HRT are what?

Standard dosage of Oral estrogen, such as 0.3-0.625 mg of conjugated equine estrogens 0.5 mg oral estradiol 0.025 mg transdermal estradiol, Higher doses may be necessary to relieve hot flashes. *** Progressive reduction of dosage should be attempted as soon as feasible *** Additional formulations containing estradiol, synthetic estrogens, and estrogens plus progestins are also available

What is osteoporosis?

Systemic skeletal disorder characterized by: Low bone mass Microarchitectural deterioration of bone tissue, Increase in fragility of bone Susceptibility to risk of fracture. Although gradual bone loss occurs in all humans with aging, this loss is accelerated in women after cessation of ovarian function. After attainment of peak bone mass by age 25-30 years, bone loss begins, accelerates in women at menopause, and then slows again but continues into advanced years at a rate of 1-2% per year Women can lose up to 20% of their bone mass in the 5-7 years after menopause.

Diagnosis & Monitoring for osteoporosis involves what?

TOC - DEXA scan Bone mineral density (BMD) results are reported using T and Z scores. T score = number of standard deviations (SD) above or below the mean bone mineral density for sex-matched young normal controls. Z score = compares the patient with an age- and sex-matched population. Normal bone density is defined as a T score > -1.0 SD at the spine, hip or forearm. Osteopenic = T scores -1.0 to -2.5, osteoporotic = T scores < -2.5.

The FDA has declared that claims of compounding pharmacies; stating ?

That BHT drugs avoid the risks of FDA-approved treatments and these drugs reduce the risk of serious illness such as heart disease, stroke, or breast cancer are not supported by credible scientific evidence. They further state that safety and efficacy of estriol in these formulations has not been proven.

Decades of mature reproductive life are characterized by a generally regular menses and a slow, steady decrease in cycle length that looks like what?

The decrease noted at 35 years+ is a result of shortening or the follicular phase of the cycle, with the luteal phase length remaining constant

What is Postmenopausal Period (stage +1)

The first 6 years following the final menstrual period (FMP) 12 months following the FMP marks the end of the menopausal transition FSH continues to increase

Bio-identical Hormone Therapy

These hormones do not approximate your hormones; they have the same exact chemical structure as the hormones made by ovaries. Supporters argue that, d/t same structure the body should be better equipped to work with them. The argument, typically, is that we can more easily metabolize them and break them down so our livers and kidneys can excrete them once they've done their work. Cenestin is a conjugated estrogen. It's natural in that it's made from plant sources, but it's not bio-identical to human estrogens. It's the plant-based copy of Premarin. Natural estrogens include: Estrace, Estratab, Ogen, the estradiol patches such as Climara, Alora, Vivelle,Estraderm, Esclim, FemPatch, etc, Tri-Est

Hormone Replacement Therapy contraindications?

Undiagnosed abnormal Vaginal bleeding Known, suspected, or hx of breast cancer Active DVT, PE or hx of these conditions Arterial thromboembolic disease (MI, Stroke) Liver dysfunction/dz

What are atrophic vaginitis S&S?

Vaginal Complaints Pruritus, burning, soreness, dyspareunia, Leukorrhea, thin watery or serosanguineous discharge. Minimal trauma with examinations or coitus may result in slight vaginal bleeding. Urinary complaints: Urinary frequency, urgency, dysuria, and urge incontinence,

Atrophic guidelines for HRT are what?

Vaginal preparations are preferred over systemic estrogens These preparations are available in the form of: Creams (ie, CEEs or estradiol 0.25-2 g PM for 2 weeks, followed by twice weekly), Tablets (10 μg estradiol given nightly for 2 weeks, followed by twice weekly) Rings (estradiol releasing rings, which remain in place for 3 months at a time) *** With the tablets, rings, and lowest dose creams, endometrial proliferation is RARE.***

Short term vs. Long term Risk of HRT includes?

Women who have been receiving long-term estrogen-progestin hormone replacement therapy, even in the absence of complications, should be encouraged to stop, especially if they do not have menopausal symptoms.

Hot flushes are a greater annoyance than most physicians recognize. Patients frequently complain of night sweats and insomnia. There is a close relationship between hot flushes occurrence and nighttime awakening. What might this lead to?

Women with frequent flushes may experience flushes and awakenings hourly, which may cause profound sleep disturbance that may in turn, cause cognitive (memory) and affective (anxiety) disorders.

A 52-year-old female presents with a primary complaint of amenorrhea for the past 6 months. She also reports dyspareunia, recurrent headache, and infrequent episodes of night sweats. Diagnostic work-up reveals increased serum FSH levels. Which additional laboratory findings would most likely be seen in this patient?

a. Increased estradiol & decreased LH b. Increased progesterone & increased LH *c. Decreased estrogen & Increased LH* d. Decreased Progesterone & Increased testosterone

How is Progestin-Estrogen Therapy administered?

administer a progestogen 12-14 days each month If this is accomplished, 80-90% of women will experience some vaginal bleeding Administer a lower dosage, 2.5 mg, continuously. Many newer formulations of hormone therapy contain both estrogen and progestin The combined, continuous administration of estrogen plus progestogen is the most common mode of administration today.

This regimen promotes endometrial atrophy results in what?

amenorrhea in 70-90% if used for more than 1 year. The remaining 30-10% will bleed occasionally, bleeding usually being less frequent, shorter, and lighter than with sequential therapy. Other SE's" fatigue, depression, breast tenderness, bloating, cramps, HA's, Inc risk of breast cancer!

Atrophic and Recurrent Cystitis characterized by what?

characterized by urinary urgency, frequency, incontinence, and dysuria.

What is menopasue?

diagnosed after 12 months of amenorrhea with no obvious pathologic cause

Menopause =

final menstruation

What is sexual dysfunction?

hypo-estrogenic state leads to atrophy of the internal genitalia. Symptoms of vaginal atrophy include: Dyspareunia (painful intercourse) suboptimal sexual functioning Diminished genital sensation (and therefore decreased sensory output in the arousal phase) Lessened glandular secretions, Decreased vaginal expansion

Many women express a preference for bioidentical hormones (BHT), with the expectation that they are safer, with comparable efficacy Varying formulations which are not used consistently amongst patients or practitioners Bioidentical hormones are plant-derived compounds that have the same chemical and molecular structure as those of hormones produced by the human body. Pharmacists can custom prepare and package (compound) bioidentical hormones according to a physician's specifications. After results of the WHI were reported in 2002, interest in bioidentical hormones does what

increased b/c they have been promoted as a safer alternative to traditional hormone therapy, with the ability to tailor dosages of various estrogens. Although the existing studies on bioidentical hormones have not shown an increase in breast cancer, these studies have been too short in duration or methodologically flawed to show changes. These findings have unfortunately been interpreted as proof of safety rather than as inconclusive. This may be misleading to the public.

Premature menopause =

menopause reached at or before age 40 and can be natural or induced

Perimenopause/menopause =

menstrual cycle and hormonal changes that occur a few years before and 12 months after the final menstrual period resulting from natural menopause. the menstrual cycle is likely to be irregular and when other symptoms or complaints may be experienced.

Induced menopause =

permanent cessation of menstruation after bilateral oophorectomy or ablation of ovarian function (ie, by chemotherapy or radiation)

Postmenopause =

phase of life that comes after the menopause.

Bone loss produces minimal symptoms, but leads to reduced skeletal strength. Thus osteoporotic bones are more susceptible to fractures. Most common site of fractures are?

vertebral body, proximal femur, distal forearm/wrist.

According to the 2010 US census, of the 155 million women in this country, 41 million were 55 years of age or older. Most of these women had or shortly would have their last menstrual period, thus becoming postmenopausal. how long will a women on average live after menopause?

woman at age 55 years can expect to live another 28 years, a large portion of the female population is without ovarian function and lives about one-third of their lives after this function ceases. "Consequently, physicians caring for women must understand the hormonal and metabolic changes associated with the menopause, or "change of life," and the potential benefits and risks of hormone therapy (HT)."