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GYN Clinical update. Cervical Cancer Screening and Pap Management Update Abnormal Uterine Bleeding Management of Menopausal Symptoms. Cervical Cancer Screening and Pap Management Update. US Cervical CA prevalence has decreased by > 50% in past 30 years 14.8/100,000 patients in 1975
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GYN Clinical update Cervical Cancer Screening and Pap Management Update Abnormal Uterine Bleeding Management of Menopausal Symptoms
Cervical Cancer Screening and Pap Management Update • US Cervical CA prevalence has decreased by > 50% in past 30 years • 14.8/100,000 patients in 1975 • 6.6/100,000 in 2008 • Mortality has been reduced from 5.6/100,000 in 1975 to 2.4/100,000 in 2008 • 60% of new Cervical CA cases estimated to be as a result of inadequate screening • 50% with no screening • 10% without screening for 5 years • Highest risk in immigrants, low income, uninsured
HPV • Oncogenic vs non-oncogenic • Oncogenic usually associated with CIN 2+ • Transient vs persistent. Most HPV infection is transient • HPV-16 most oncogenic – 60% of CA cases • HPV-18 is next – 15% • Approximately 10 other HR subtypes • Risk Factors for persistence: • Cigarette smoking • Immunocompromised • HIV infection
HOW to test? • Conventional vs Liquid both acceptable
When to begin Testing?16? Sexual Activity? 19? 21? • Begin screening at age 21, regardless of previous sexual activity • Cervical CA risks <0.1% at ages ≤ 20
When to Test?Ages 21-29 • Every 3 years with Pap only: no co-testing with HPV • High prevalence of HR HPV < age 30 with low CA risk • 80% lifetime cumulative risk of HPV infection • High clearance rates in this age group • Average time to HPV clearance of new infection for age group – 8 months • 90% reduction in viral loads within 2 years • No significant difference between 1 and 3 yr. intervals with outcome • Past? – yearly testing by 19/21 or with sexual activity, more aggressive testing via colposcopy and biopsy, higher interventions via LEEP/cryo for mild-moderate dysplasia at younger ages with morbidity in a condition likely to resolve
When to Test?Ages 30-65 • Option 1: Every 3 years with Pap alone - no co-testing with HPV • Option 2: Every 5 years with pap and HR HPV co-testing • Pooled European Data: • 0.28% risk of CIN 3 within 6 years with (-) Pap and (-) HPV • 0.51% risk of CIN 3 within 3 years with (-) Pap alone
When to Test?Ages >65 • 14% of Cervical CA occurs at > 65 – majority in unscreened women • Average time from persistent HR HPV to CA 15-25 years • Screening q 3yrs until age 90 results in the lifetime prevention of 16 cancers per 10,000 women screened with significant cost and morbidity • Therefore, current recommendations are to stop Pap screening at age 65 for low-risk patients
Other screening tips • Total Hysterectomy (no residual cervix) • Primary vaginal cancer is the rarest of GYN malignancies • No prior history of ≥ CIN 2: • stop routine cytology screening and HPV testing and don’t restart for any reason. • Prior history of ≥ CIN 2: • Continue vaginal screening with cytology alone (no HPV) every 3 years for 20 years after the initial post-treatment surveillance time interval, even if > age 65
Other screening tips • Encourage HPV vaccination for all males ages 9-21 and females ages 9-26. • Utilize more rigid screening criteria for HIV (+), In-utero DES exposure, previous history of ≥ CIN 2, and immunocompromised patients • Unsatisfactory Pap result with no, unknown, or negative HR HPV testing: • Repeat in 2-4 months. Triage with HPV testing is not recommended • Treat atrophy or vaginal infection, if present, prior to rescreening • Unsatisfactory Pap with (+) HR HPV and age ≥ 30: • Repeat in 2-4 months as listed above • Colposcopy acceptable • Colposcopy recommended if two consecutive “unsatisfactory” pap tests • HPV screening, in lieu of cytology, not currently recommended due to lack of outcome data
Practical pearls • Encourage HPV vaccination, if age appropriate • Educate to overcome “traditional” Pap screening biases • Educate on full women’s Health review rather than “follow-up in one year for your Pap” mentality • Counsel with and listen to your patients. More frequent Pap exams (and other testing) may be appropriate
AUB – Abnormal uterine bleeding • Reproductive-Aged (Premenopausal) • Old but common terminology • Menorrhagia – heavy menstrual bleeding, regular • Metrorrhagia – bleeding at irregular intervals • Menometrorrhagia - irregular and heavy bleeding • Polymenorrhea – Bleeding at ≤ 21 day intervals • Oligomenorrhea – Bleeding at ≥ 35 day intervals • Amenorrhea – extended absent bleeding • PCB – post coital bleeding • New classification system introduced in 2011
Palm-coein • Classifies uterine bleeding abnormalities by bleeding pattern as well as by etiology • AUB is paired with descriptive terms such as “heavy menstrual bleeding (instead of menorrhagia), and intermenstrual or irregular bleeding - (instead of metrorrhagia) • AUB is further classified by one or more letter-qualifiers that indicate etiology • Term dysfunctional uterine bleeding (DUB) should be discontinued, per recommendations
Fig. 1 Basic classification system. The basic system comprises 4 categories that are defined by visually objective structural criteria (PALM: polyp; adenomyosis; leiomyoma; and malignancy and hyperplasia), 4 that are unrelated to structural... FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age International Journal of Gynecology & Obstetrics Volume 113, Issue 1 2011 3 - 13
Evaluation - History • Mean Volume – 40 ml (95% CI <60cc) • > 80 ml whole blood defined as abnormal • Subjective Assessment Accuracy? • How accurate are patients in estimating blood loss? • 1/3 patients reported “light” bleeding - >80cc • ½ patients reported “heavy” bleeding < 80cc (Chimbira TH et al: Br J Obstet Gynaecol 87:603, 1980.)
Evaluation - History • Is objective measurement important? • Four questions to easily assess AUB and to gauge how the patient perceives her menstrual bleeding: • How are your periods? • How many days do they last? • Do you think they are heavy? • Do you periods disrupt you life?
Evaluation - History • Documentation: • Types of protection used • frequency of protection changes • amount of soiling • # of heavy days • total bleeding days/month • amount of ADL dysfunction • associated symptoms (i.e. fatigue, pain, etc.) • previous treatments (successes and failures) • further childbearing desires • previous or desire for sterilization
Evaluation - Diagnosis • Careful History • Relationships with menses, stress, ROS? • Menstrual calendar/log • Laboratory Studies: CBC, Chem-12, TSH, Pregnancy test, bleeding disorders
Evaluation - Diagnosis • Studies • Ultrasound • Saline Infusion Sonography (SIS) • Hysteroscopy +/- D&C • Biopsy • Bleeding Log/calendar • MRI
TVUS Aub- algorithm
Aub – treatments • OCP’s • Monophasic OCP's frequently effective (high, mid, low, and very low dose) • Subjectively highly effective for mild AUB from a variety of etiologies • Typically need 3-4 months of use to assess efficacy • Progestins • Alternative to OCP’s for long-term treatment of anovulatory AUB • Mirena IUD for ovulatory bleeding (off label use) • Cyclic progestins are most effective with ovulatory dysfunction • Allows organized sloughing • Side effects related to dose – wt gain, edema, water retention, mood changes, etc.
Ablation • Highly effective: success defined as a reduction in blood loss or amenorrhea of over 90% • Reduction in flow~ 60+% • Amenorrhea ~ 30-40% • Indicated for treatment of AUB including menorrhagia and “patient perceived heavy menstrual bleeding” • Outpatient with fast recovery • Some in-office opportunities • Varying degrees and time of patient preparation
Hysterectomy • Generally a treatment of last resort for AUB • Definitive • Newer minimally invasive techniques have narrowed the gap in tolerance, recovery, and risk compared to ablation • Laparoscopic routes have allowed the shortening of recovery by 2-4 weeks compared to the traditional abdominal and vaginal routes
Aub – treatments My current VA practice utilizes these minimally hysterectomy invasive techniques in roughly 90-95% of non-malignant cases. Full recovery times, including return to work, exercise, intercourse, etc can be in as little as 7-10 days for laparoscopic supracervical hysterectomy procedures with an outpatient (<23-hour) hospital stay.
Menopause • Avg Age – 51 in Caucasian, non-smoking women • Climateric transition and associated fluctuations in ovarian function can last up to 5 years or more and is highly variable • Characterized by low estradiol and progesterone levels with elevated FSH concentrations • Other manifest symptoms often include some degree of mood alterations, altered sleep patterns, poor memory, “a brain fog”, changes in sexuality….
Treating Menopausal Symptoms The Big Two • Vasomotor Symptoms • Vaginal Irritation/Atrophy
vasomotor symptoms • Up to 80% of woman with Natural Menopause experience hot flushes or hot flashes • Generally peaks 1-yr after menopause begins (cessation of menstrual cycles for 1 full year) • Stereotypically manifests as a sudden sensation of extreme heat, with or without perspiration, typically in the upper chest, face, and neck lasting 1-5 minutes in length • 97% have daily manifestations • Median duration is 4 years
Vasomotor Treatments • Repeatedly, systemic estrogen has proven to be the most effective therapy (ERT/HRT) • Cochrane Meta-analysis: 75% reduction in weekly # of Hot Flash episodes, including reduced severity • Routes: oral, topical, injections • Forms: tabs/capsules, patches, gels, sprays
Vasomotor Treatments General Dosing Principles: Lowest Effective Dose to relieve symptoms - No proven benefit with chasing hormonal levels
Vasomotor Treatments • WHI: Women’s Health Initiative • Not cardioprotective • Small Increased breast CA (combined therapy), CAD, CVA, VTE with combination HRT • Decreased fracture risk and small decrease in colon CA • Mean age of study participants was well beyond menopause • (Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. Writing Group for the Women’s Health Initiative Investigators. JAMA 2002;288:321–33.)
Vasomotor Treatments • More Recent re-analysis of WHI for women <60 and within 10 years of menopause: suggested a mild cardioprotective effect with less calcified-plaque burden with ERT (Manson JE, Alli2007;356:2591–602son MA, Rossouw JE, Carr JJ, Langer RD, Hsia J, et al. Estrogen therapy and coronary-artery calcification. WHI and WHI-CACS Investigators. N Engl J Med. (Level I)) • A 2012 Cochrane review of HRT reaffirmed the recommendation that HRT should not be used for 1° or 2° prevention of CV disease or dementia as risks outweigh benefits(avg age in these 23 studies was >60)(Marjoribanks J, Farquhar C, Roberts H, Lethaby A. Long term hormone therapy for perimenopausal and post-menopausal women. Cochrane Database of Systematic Reviews 2012, Issue 7. Art. No.: CD004143. DOI: 10.1002/14651858.CD004143.pub4. (Meta-analysis)
when to stop? ACOG recommendation: “The decision to continue HT should be individualized and be based on a women’s symptoms and the risk-benefit ratio, regardless of age……and recommends against the routine discontinuation of systemic estrogen at age 65”(Practice Bulletin #141, Jan 2014)
HRT Options • Combined HRT (estrogen + progestin) • Estrogen • Oral Estrogen (conjugated vs micronized estradiol) • Transdermal estradiol (patch, gels, spray) • Progestin • MPA (provera) • Norethindrone (aygestin) • Micronized progesterone (prometrium) • Compounded • Combined vs individual dosing, transdermal vs oral, high vs standard vs low vs ultra-low dosing
HRT Options • ERT • Oral Estrogen (conjugated vs micronized estradiol) • Transdermal estradiol (patch, gels, spray) • Progestin alone • Multiple studies have shown a mild (+) effect of progestins on reduction of vasomotor sx’s • Unclear breast CA risks based on inference • Most studies have used MPA, not micronized progestin
HRT Options • Oral conjugated estrogen and Bazedoxifene (Estrogen agonist/antagonist) • FDA approved for relief of vasomotor sx’s and prevention of osteoporosis in postmenopausal women with a uterus • An alternative to adding progestin to an ERT regimen • Testosterone • Alone – no benefit with meta-analysis review on vasomotor sx’s with potential adverse effects on lipids, acne, hirsutism, etc • Combined with ERT – improvement in sexual function assessments • Not FDA approved as stand-alone therapy for women
hrt options • Compounded “Bioidentical” Hormones • “Because of a lack of FDA oversight, most compounded preparations have not undergone any rigorous clinical testing for either safety or efficacy, so the purity, potency, and quality of compounded preparations are a concern. In addition, both underdosage and overdosage are possible because of variable bioavailability and bioactivity. Evidence is lacking to support superiority claims of compounded bioidentical hormones over conventional menopausal HT (this is also discussed in Committee Opinion Number 532, Compounded Bioidentical Menopausal Therapy). ”
other Options • SSRI’s/SSNRI • Desvenlafaxine: 62% of women treated (100mg/day) had a reduction of 5 moderate-to-severe hot flashes/day compared to 41% of placebo users with >1-yr of treatment (Pinkerton JV, Archer DF, Guico-Pabia CJ, Hwang E, Cheng RF. Maintenance of the efficacy of desvenlafaxine in menopausal vasomotor symptoms: a 1-year randomized controlled trial. Menopause 2013;20:38–46.) • Paroxetine (7.5mg/day) is the only FDA approved non-hormonal therapy for vasomotor sx’s • Clonidine: limited data, 0.1mg/day, meta-analysis with small benefit
other Options • Gabapentin (600-900mg/day) • Mild reductions in frequency and severity of hot flushes • Phytoestrogens, Herbal and other remedies • Soy, red clover extract, ginseng, black cohosh, ginkgo biloba, vitamins, acupuncture, Saturday morning talk radio…………………………..????
Vaginal dryness and atrophy • Estrogen Works! • Localized vaginal tablet, cream, sustained release ring • Low dose effective (10mcg vs 25mcg tablets) • Dosing with tablet or creams: nightly for 5-7 days then 1-2 times/week • Progestin therapy not necessary • Use with a history of Breast CA…
Vaginal dryness and atrophy • Estrogen Agonist/Antagonist • Ospemifene is FDA approved for the treatment of moderate-to-severe dyspareunia in postmenopausal women at a dose of 60mg/day • Raloxifene and tamoxifen to proven to be effective • Lubricants and moisturizers have some measure of success