Kembara Xtra - Medicine - Menopause
Natural menopause is defined as 12 consecutive months of amenorrhea in a non-pregnant woman under the age of 40, with a mean age of 51. Perimenopause/menopausal transition (MT) is the time between the start of irregular menstruation and the last monthly cycle. starts at a mean age of 47 years, 4 years before menopause, on average. Primary ovarian insufficiency is the irregularity or cessation of ovulatory cycles before the age of 40 years. Surgical menopause is the removal of functioning ovaries, which causes rapid menopause. Menopause typically occurs between the ages of 51 and 55 for women, with another 5% of women going through it between the ages of 40 and 45. In comparison to Caucasians, menopause strikes Hispanic women earlier and Japanese American women later. Incidence Every year, 1.3 million women in the US experience menopause. Pathophysiology and Etiology Ovarian estrogen production fluctuates and then declines as women age, resulting in a reduction in the number of ovarian follicles. The production of follicle-stimulating hormone (FSH) fluctuates before increasing. Anovulation is brought on by insufficient estradiol synthesis, which prevents the luteinizing hormone (LH) spike from occurring. Progesterone production is reduced as a result of anovulatory failure, which also causes the endometrial lining to shrink and finally stop producing estradiol. During menopause, adipose tissue-produced estrogen becomes the predominant type of the hormone. Risk factors include smoking (earlier age of onset by two years), aging, oophorectomy/hysterectomy, and sex chromosomal abnormalities (such as Turner syndrome and fragile X syndrome). Low body mass index, pelvic radiotherapy, and/or chemotherapy Basic Prevention Menopause is a natural occurrence that cannot be avoided. It is linked to a higher risk of long-term health problems, such as osteoporosis and cardiovascular disease (CVD). Reduce CVD risk by: - Increasing exercise - Preserving a healthy weight and diet - Refraining from smoking - Treating diabetes mellitus, hypertension, and hyperlipidemia - Weight-bearing activity and fall prevention - Avoiding smoking and drinking too much alcohol - Dietary calcium of 1,200 mg/day - Adequate vitamin D intake (800 to 1,200 IU daily) - Reduce risk of osteoporotic fractures Clinical diagnosis: 12-month amenorrhea in a woman who is not pregnant and is under 40 years old. History - Usually preceded by a period of irregular periods with excessive vaginal bleeding, followed by reduced vaginal flow. - 80% of people report having vasomotor symptoms. - A sudden, uncomfortable sensation of heat and sweating that usually affects the face, neck, and chest and lasts for one to five minutes at random intervals. - In general, they start 2 years before the last menstrual cycle, peak one year after, and then decline. - Flushes occur on average every day for 87% of women who report them, with 33% reporting more than ten per day. The average length of the symptoms is 4 to 10.2 years, and they can start during MT and remain well past menopause. - largest in African American and Hispanic women, and least common in Asian women; more prevalent in fat women Menopausal genitourinary syndrome: 50% of women experience vulvovaginal atrophy. Dryness/itching of the vulvar area, dyspareunia, and potential sexual dysfunction Atrophy and an alkaline vaginal pH enhance the incidence of UTIs and vaginal infections. With aging, persists or gets worse Anxiety/depression: Some studies demonstrate a new diagnosis of depression is 2.5 times more likely to occur during the MT as compared to premenopause. Urologic symptoms (urgency, frequency, dysuria, incontinence) are not clearly connected with MT. Changes in migraine strength and severity, skin thinning, minor hirsutism, and brittle nails are all associated with menopause. Sleep disturbances include waking from sleep, persistent sleep disruption, and chronic insomnia. Considerations for the Elderly Because postmenopausal women's vaginal bleeding is atypical, endometrial cancer and endometrioid adenocarcinoma (EAC) must be ruled out. Clinical examination reveals a reduction in breast size and a change in the texture of the breasts. A genitourinary exam reveals an atrophic vulva and mucosa, which increases the risk of uterine prolapse. Multiple Diagnoses Anorexia nervosa, Asherman syndrome, thyroid disorders, pituitary adenoma, Sheehan syndrome, hypothalamic dysfunction, pregnancy, and obstruction of the uterine outflow tract Laboratory Results Initial examinations (lab, imaging) The diagnosis of menopause is made based on the patient's age and symptoms, not on laboratory tests. If premature/early menopause is suspected or to rule out alternative reasons of oligo-/amenorrhea, lab tests should be performed by age 45: - Symptoms may occur before lab changes; elevated blood FSH level >30 mIU/mL implies ovarian failure. ● Infertility evaluation: may employ elevated day 3 FSH, decreased anti-müllerian hormone levels, and decreased antral follicle count to suggest decreased ovarian reservOral contraceptive pills (OCPs), androgens, and estrogens can all affect lab findings.. Tests in the Future & Special Considerations Test for pregnancy TSH and prolactin levels should be checked if pituitary dysfunction is suspected. TVUS and/or EMB testing should be done on any abnormal uterine bleeding, including postmenopausal hemorrhage. EAC is unlikely if the endometrial stripe is less than 5 mm on TVUS. The U.S. Preventive Services Task Force (USPSTF) advises women aged 50 to 74 to get a mammogram every two years. Using the FRAX tool to determine fracture risk, available at https://www.sheffield.ac.uk/FRAX/, the USPSTF advises postmenopausal women >65 years of age should have bone mineral density (BMD) screening with a dual energy x-ray absorptiometry (DEXA) scan. Fractures in the past, being underweight, smoking, and having a family history of osteoporotic fractures are all risk factors. Interpretation of Tests Results of abnormal BMD and DEXA scans: - A DEXA T-score of 1 to 2.5 indicates osteopenia; a T-score of 2.5 indicates osteoporosis; defer to the femoral neck Score T over the spine T-score. Age-matched mean bone density is measured using the Z-score (not clinically relevant). management in the lead The most effective treatment for genitourinary and vasomotor symptoms of menopause is hormone therapy (HT), which has also been proved to stop bone loss and fractures. It is crucial to create a personal risk-benefit profile. The purpose of treatment is to reduce menopausal symptoms and enhance quality of life. The dangers of long-term hormone replacement therapy (HRT) use outweigh the advantages in terms of endometrial, breast, and ovarian cancers as well as venous thromboembolism, cardiovascular disease (CVD), and gallbladder disease. ● Benefits are more likely to exceed risks in women under the age of 60 or those who are within 10 years of the beginning of menopause if shared decision-making results in the introduction of HRT following a discussion of risks and benefits. ● The treatment of moderate to severe vasomotor symptoms is the main indication for HT. - Oral estrogen or an estrogen-progestin combination can cut back on hot flushes by 75% on a weekly basis. HT decreases the risk of osteoporotic fractures, urogenital atrophy, and interrupted sleep. Because unopposed estrogen carries a higher risk of EAC, progestin should be given to women who still have their uterus intact. Among the treatment plans are, but are not restricted to: Low dose: CEE 0.30 to 0.45 mg/day OR micronized estradiol 17 0.5 mg/day OR transdermal estradiol 17 0.025 mg/day - Ultra-low dose: micronized estradiol 17 0.025 mg/day OR transdermal estradiol 17 0.014 mg/day - Micronized progesterone 100 mg/day can be used as progestin. Medroxyprogesterone acetate (MPA), 2.5 mg/day, is an alternative. Levonorgestrel or norethindrone are the two progestin sources used in transdermal combination estradiol/progestin therapy. The intrauterine system (IUS) containing levonorgestrel has been utilized, despite not being approved for postmenopausal women. - Tissue-selective estrogen complex, which consists of bazedoxifene (selective estrogen receptor modulator [SERM])+ conjugated estrogens, protects the endometrium without the need for progesterone to treat vasomotor symptoms and prevent bone loss. Breast soreness, vaginal bleeding, bloating, and headaches are less concerning side effects. ● The North American Menopause Society (NAMS) offers the MenoPro software for free for iPhone and iPad users. To support collaborative decision-making, it offers two modes: one for physicians and one for patients. Users can advance through the questions to assess the risk of cardiovascular and reproductive organ cancer. The American College of Obstetricians and Gynecologists (ACOG) advises that HT be administered on an individual basis, using the lowest effective dose for the shortest amount of time necessary to treat vasomotor symptoms. For many patients, symptom reduction profiles at lower doses are comparable. Ultra-low-dose regimens have a mixed record of success. Safety measures: Women who took CEE with MPA compared to placebo had higher rates of coronary heart disease (CHD), invasive breast cancer, stroke, pulmonary embolism, dementia, gallbladder disease, and urinary incontinence; benefits included lower rates of diabetes, hip fractures, and vasomotor symptoms. Breast cancer risk was not noticed until five years after starting treatment. Women taking estrogen alone had no increased risk of invasive breast cancer, but they did have an increase in abnormal mammograms necessitating further research. - Since the risks outweigh the benefits, HRT should not be taken for cardioprotective purposes. - Higher estrogen doses have been linked to hypercoagulability, gallbladder disease, and hypertension. - Contraindications to HT include: Cancers that depend on estrogen Undiagnosed endometrial hyperplasia or abnormal uterine bleeding, as well as a history of thrombosis or stroke ○ CAD Active liver illness Uncontrolled high blood pressure Breast cancer, present or former ● For osteoporosis, it is advised to utilize pharmacologic therapy since the advantages outweigh the dangers in treating postmenopausal women who are at high risk for fractures, particularly those who have recently fractured. Women who have experienced a hip fracture, a vertebral fracture, or who have a personal history of osteoporosis should be given one of the following treatments: - Bisphosphonates to prevent bone resorption and osteoclast activity: Risedronate: 35 mg once a week or 5 mg daily; Alendronate: 70 mg once a week or 10 mg daily Ibandronate: 150 mg/month PO or 3 mg IV every three months Zoledronic acid: 5 mg IV annually - SERMs specifically block or promote estrogen-like activity when osteoblasts are stimulated: Reduces the incidence of vertebral fracture: Raloxifene, 60 mg/day Denosumab (60 mg SC every 6 months) is a monoclonal antibody that prevents receptor activator of nuclear factor-B ligand (RANKL) from accelerating osteoclast generation, which lowers the incidence of vertebral and hip fractures in postmenopausal women. Bazedoxifene + conjugated estrogens (0.45 mg/20 mg) is a combination FDA-approved for moderate to severe vasomotor symptoms and osteoporosis. - Parathyroid hormone, which is infrequently used since it has a negative impact on bones but has been found to lower the incidence of fracture in menopausal women with osteoporosis. Topical estrogen therapy (ET) for vulvar/vaginal atrophy reverses vaginal atrophy, improves blood flow, and lowers UTI. Continue for however long the uncomfortable symptoms last. Start with daily treatment for the first one to two weeks, then cut back to twice weekly. estradiol is available as a cream, pill, or ring. There is no proof that the various intravaginal estrogenic formulations differ in their effectiveness. Utilize vaginally: Vaginal ring (7.5 g daily for three months), vaginal pill (10 g), conjugated estrogen 0.625 mg/g, and estradiol cream (0.01%, 1 g). Ospemifene: 60 mg PO daily; SERM for moderate to severe dyspareunia related to vaginal atrophy. For some people, nonestrogen vaginal lubricant may be just as helpful as topical estrogen. Next Line Treatments other than hormones may be effective for vasomotor symptoms: It is legal to use paroxetine (10 to 25 mg/day) to treat vasomotor symptoms. This SSRI showed a slight reduction in hot flushes. In comparison to placebo, venlafaxine (37.5 to 100.0 mg/day), fluoxetine (20 mg/day), and citalopram (20 mg/day) have been demonstrated to lessen hot flashes. When compared to a placebo, gabapentin (300 to 900 mg/day) has been demonstrated to have an impact in reducing hot flushes. Less effective than SSRI/SRNIs, clonidine (0.05 mg BID) may be used to treat moderate hot flashes. Be aware that the majority of second-line therapy trials have been short-lived (a few months). Alternative Therapies In comparison to a placebo, phytoestrogens, herbs, and other supplements don't seem to help with menopause symptoms. Some should be used with caution since they may interact with anticoagulants like warfarin. For some people, hypnotherapy and mindfulness meditation may be helpful. Yoga has not been proved to treat hot flashes but may be helpful for other menopause-related symptoms. Acupuncture has not been shown to be more effective than simulated acupuncture for reducing hot flashes. Given safety issues, including the likelihood of overdosing or underdosing, a lack of efficacy and safety trials, and a lack of a label indicating dangers, compounded bioidentical HT should be avoided (1). Overall, the majority of data come from short-term trials, therefore there is little information on their long-term safety. However, mind-body techniques like hypnosis, yoga, meditation, and acupuncture generally have strong safety records. Patient Follow-Up Monitoring If HRT is started, consider reducing or stopping after 3 to 5 years to minimize risks. A DEXA scan in women at age 65 with risk equivalent to age 65. Based on the patient's symptoms and medical history, ACOG advises that the choice to stop or continue HT be made individually. A diet high in calcium and vitamin D supplements (800–1,200 IU/day). The risk of kidney stones and cardiac problems may rise with taking calcium supplements. Changes in lifestyle include quitting smoking and drinking less alcohol, increasing exercise to at least 30 minutes three times a week, maintaining a healthy diet, and addressing changes in cardiovascular risk factors. The prognosis is: if left untreated, vasomotor symptoms will eventually go away; vaginal/vulvar atrophy will worsen; and osteoporosis will develop. Complications Osteoporosis: Accelerated bone loss during 5 to 7 years, up to 3-5% every year. Increased CVD risk after menopause
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