Top 10ish Women’s Health Articles of 2015-16

Rebecca Jackson, MDObstetrics, Gynecology and Reproductive SciencesUCSF

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Articles that might change practice or topics in the news

Mostly gyn, a little obBread and butter: menopause,

dysplasia, contraception, miscarriage

Menopause: 3 studies

in the subgroup of younger women….

MHT (aka HRT) and CVD in younger menopausal women

Meta-analysis of RCTs looking at subgroup who started MHT less than 10 years after menopause

Oral only (transdermal not evaluated)5 trials and 9088 participants

Death (all cause): Decreased 30%, NNT 146

Coronary Heart Disease: Decreased 48%, NNT 133

Summary of benefits and harms in younger women

NNH: 214

NNH: 133

NNH: 146

Bottom Line: HRT in younger postmenopausal women appears to reduce mortality and CVD but with an increase in VTE and stroke.

Not recommended for prevention of heart disease due to risks

Caveat: The follow-up time is lumped (rather than year by year). Some evidence suggests an early increase in CVD in predisposed women.

80% of women experience vasomotor sx (VMS), most rate them moderate to severe

Older studies and guidelines reported VMS continue 6 mos to 2 yrs after LMP

2 outcomes: total duration of frequent VMS (perimenopause included) and duration after menopause.

Frequent VMS= 6 or more days in 2 wk period; hot flashes or night sweats

VMS=vasomotor symptoms

SWAN: Study of Women’s Health Across the Nation17yr cohort of 3300 multi-racial/ethnic women enrolled at 42-52 yo, excluding menopausal, on ocp or hrt, hysterectomy

Total VMS duration: 7.4 years, after LMP 4.5 years (ie 2 yrs VMS while perimenopausal, 5 more years after menopause)

Onset of VMS: If VMS start during pre or early perimenopause—longer overall duration (>11.8 yrs!); if start after menopause, shorter duration (3.4 yrs)

Race/Ethnicity: AA women had longest duration (10 yrs); Japanese and Chinese women had the shortest 4.8 and 5.4 years, respectively). Non-Hispanic White=6.5; Hispanic=8.9

Duration increased with stress, depression/anxiety, younger age, lower educ

VMS=vasomotor symptoms

SWAN: Study of Women’s Health Across the Nation: 17yr cohort of multi-racial& ethnic women enrolled at 42-52 yo

How often do your patients complain that menopause is causing moodiness, depression, irritability or decreased ability to concentrate or perform?

Is HRT the answer?For Cognition: No. (no sig diff in any

cognitive outcome)For Mood: Maybe, modest improvement

in some sx, for oral E+P only (improved sxof anxiety, depression, anger)

KEEPS: Kronos Early Estrogen Prevention StudyRCT of oral or transdermal E+P vs placebo in recently menopausal women, n=693, 4 yrs f/u

Ala Kahakai TrailAncient Hawaiian TrailAccess it at left side of

beach—walk inland along rocks and you will see it

Goes to Beach 69 (25 min) and beyond to Puako (1 hr)

Hot, rocky, look for cairns to find trail in places

~20% of those infected become ill. Incubation few days to 2 wks. (4-10 days)Common Sx: acute onset of fever, maculopapular

rash, arthralgia, conjunctivitis (50%); Less common: myalgia, headache, retroorbital pain, pruritus, and vomiting

Typically mild and lasts several days to 1 week.Guillain-Barre-possible but rare. (<<1% of infected)

Other modes of transmission= maternal-fetal, blood transfusion, sexual (male to female only)Remains alive in semen up to 62 days

Detection: RT-PCR for viral RNA, antigen or antibodiesTest within 1 wk of sx (viral clearance can occur in 7

days)Tests performed at CDC and limited state DPH’s. Up to date info at CDC website

As of july 6

Get update at CDC: http://www.cdc.gov/zika/geo/active-countries.html

Rapidly changing recommendations: go to CDC for latest info

Pregnant women and ZikaNot at increased risk or severity when pregnantMaternal-fetal transmission can occur any timeFetal effects: microcephaly, brain atrophy,

ventricular enlargement, intracranial calcifications. (Possible: ocular defects, scalp rugae, joint contractures.) Usually cannot diagnose until after late 2nd Tri

DEET & picaridin safe throughout pregnancy If male partner potentially exposed condoms

throughout pregnancy (and 6 months prior to conception)

NEJM July 7Risk of microcephaly greatest with infx at <18wks, Risk of microcephaly 1-13%

What’s missing in the CDC advice?……Role of abortion

“How would the results of amniotic fluid testing for Zikavirus inform clinical management of pregnant women?

A positive Zika virus RT-PCR result from amniotic fluid would be suggestive of intrauterine infection. This information would be useful for pregnant women and their health care providers to assist in determining clinical management (e.g., antepartum testing, scheduling serial ultrasounds, delivery planning).“

What’s missing in the CDC advice?……Role of abortion

Sonographic evidence of fetal transmission occurs late in 2nd trimester, early 3rd trimester. Too late for legal abortion in most states

No std definition of microcephaly, unclear neurocognitive outcome based on head size

Therefore, difficult to counsel women or recommend abortion

Nonetheless, in US, abortion should be discussed as an option (not recommended, just discussed) after suspected Zika exposure even without confirmatory testing or waiting to have sono evidence of fetus being affected

Why isn’t anyone talking about abortion?

Just this week… A link on ACOG’s website (but its about abortion in other countries). Still nothing about it in their algorithms

Zika virus outbreak: reproductive health and rights in Latin America. Latin American health ministers recommended postponing pregnancy for 6 months to 2 years 56% of pregnancies in the region are unintended Large groups of women do not have control over their

sexual and reproductive lives due to…“Poor quality of sex education, poor access to contraception, high prevalence of rape, and cultural barriers that make it difficult for women to negotiate the use of contraception with their partners.”

…”and their housing and local environments disproportionately expose them to areas that are breeding grounds for mosquitoes.

“If governments do not take this opportunity [to improve access to contraception], the Zika virus will not only be a public health issue, but also exacerbate existing gender inequalities and social injustice.

Monica Roa, Lancet, 2016

NELHA: Natural Energy Lab of Hawaii

Just past airport

Research and incubator facility

Tours: 10:00am M-F

Buy tix online

New pathologic and limited epidemiologic evidence suggests epithelial ovarian cancer arises from the Fallopian tube, not the ovaryObservational studies show decreased ovarian

cancer in women who’ve had prior tubal ligation

This is a very large, population-based study in Sweden from 1973-2009 to evaluate gyn surgery for benign reasons and risk of ovarian cancer

Linkages of Swedish nationwide health registers of all residents between hospital admissions, operations, cancer registry, death registry

Surgery from1973 to 1997251,500 women with surgery, 5.5M without

81,658 sterilization34,400 with salpingectomy, only 3051 bilateral Numbers don’t add up: “3051 women were identified with

two-sided salpingectomy and 19552 with one-sided salpingectomy”

Any salpingectomy assoc with 33% decreased risk of ovarian cancer. Unilateral 27% decrease; bilateral 54% decrease

Sterilization similar with a 31% decrease

Mounting epidemiologic evidence that tubal ligation or salpingectomy decrease risk of ovarian cancer

Caution Should we recommend this without prospective studies or better yet, clinical trials?What is risk of salpingectomy? (eg instead of a tubal

ligation or at the time of a hysterectomy)Does adding a salpingectomy to a hysterectomy

change the route of hyst to a riskier one (eg from vaghyst to laparoscopic one)

Miscarriage Prevention/Managment

PROMISE: Progesterone in Recurrent Miscarriages

Miscarriage is common: 15-25% of recognized pregnancies and associated with grief—more so than we often realize Recurrent miscarriage, 3 or more, much less common at 1-2%.

Only 50% have identifiable cause Luteal phase supplementation is beneficial for women

undergoing IVF or IUI with gonadotropic stimulation For years, patients have been given progesterone to

prevent miscarriage in spontaneous pregnancies despite a lack of evidence and no guidelines recommending this

One small meta-analysis of 4 small, methodologically challenged studies revealed a possible benefit in preventing recurrent miscarriage

PROMISE: Progesterone in Recurrent Miscarriages; 36 sites in UK and Netherlands; n=836; vaginal micronized progesterone vs placebo; <=6 wksthrough 12 wks, blinded;Outcome=live birth

All women had at least 3 prior SAbResults-Live birth rate:

66% progesterone group63% placebo groupRR 1.04 (0.94-1.15)

Bottom Line: Even in women with 3 prior sabs, chance of live birth is >60% AND progesterone doesn’t improve that

Secondary analysis of the Effects of Aspirin in Gestation and Reproduction trial

1,083 women aged 18–40 years with one to two prior early losses

Followed for up to six menstrual cycles and, for women achieving pregnancy, until pregnancy outcome.

EAGeR, Effects of Aspirin in Gestation and Reproduction

Couples with a shorter “inter-trying interval” ie 0–3-month interval (n=765 [76.7%]) vs greater than 3-month (n=233 [23.4%]) had:Higher live birth rate (53% vs 36%, p<0.001) Significantly shorter time to pregnancy leading to live

birth (median 5 cycles, range 3-8)Higher fecundability OR 1.71 (1.3-2.2)No difference in ob outcomes for women who

achieved pregnancyBottom Line: Ok to attempt pregnancy as soon as

emotionally ready

EAGeR, Effects of Aspirin in Gestation and Reproduction

Kalopa State Park

Short nature hike or up to 5 miles

Near Honoka’a, 15 miles past Waimea

Family Planning

Legislative History1. In 2011, legislature cut FP budget by 66% and

re-allocated to other programs82 FP clinics closed

2. In 2011, created 3 tiered priority system for allocating remaining funds such that specialized FP clinics were in lowest tier

3. In 2013, created state-funded program (to replace federally-funded programs) that excluded organizations affiliated with abortion providers thereby excluding all PP affiliates

Exclusion of Planned Parenthood in state administered, federally funded family planning programs has been adopted or proposed in 17 states and the US congress. Texas was the first to enact and enforce such a law.

The impact on FP services in Texas25% of state’s family planning programs closed,

31% reduced service hours Funding: Specialized FP clinics had 75%

decrease in state funds. Other clinics offering FP services also saw a 50% decrease in funding.

LARC access: In 2011, 71% of clinics offered LARC; in 2013: 46%

Confidential services for adolescents: 19% fewer clinics

Patients served: 54% fewer

Publically funded family planning clinics are a key component of the health care safety net for low-income women in the US.

Funding cuts affected both FP-only clinics (Tier 3) and DPH and FQHC primary care clinics (Tier 1/2)

The impact on women’s health in TexasContraception use

LARC : 36% decreaseDMPA : 31% decreaseOCP etc: no change

In women using DMPA:On-time re-injection 57% in 2011 to 38% in 2013 in

counties with PP (slight increase in control counties)Medicaid funded births within 18 months increased

1.9% (27% relative increase) in counties with PP; it decreased in control counties

Because of changes in funding of FP services, low income women’s choices of contraception are now constrained by the specific funding source for their care.

LARC (IUD, Nexplanon) are used less frequently in US than other countries (9% vs 23% in France)

OCP’s (failure rate of 9%) and condoms (failure rate 18%) are most commonly Rx’d methods

IUD’s generally offered to restricted subgroup (parous, married) rather than broadly to young women at risk (adolescent, nulliparous)

RCT of 40 PPFA clinics in US. Clinics randomized to receive or not receive ½ day training to integrate IUDs and implants into routine contraceptive care.Primary outcome: use of LARC, 2ndary: pregnancies within 12 months. N=1500 women

More counselling about LARC (71% vs 39%)and greater uptake of LARC (28% vs 17%; OR 1.9 (1.3-2.8)

Pregnancy rate: 15 per 100-py vs 18.5 in control group (not sig). But:

Pregnancy rate much higher in abortion clinics vs FP clinics. Stratify by type of clinic:FP clinics: 7.9 vs 15.4 per 100 person year (py); HR 0.54

(0.34-0.85)Ab clinics: 26.5 vs 22.3; HR 1.35 (0.9-2.0) NS

Bottom line: If we want to decrease unintended pregnancy, we need to be able to offer immediate access to full range of contraception, including LARC

99% of women in both groups reported autonomy in decision

LARC not as readily available in Ab clinics vs FP clinics b/c of lack of subsidized contraception. Of women choosing LARC, 44% could obtain at Ab clinic vs 73% at FP clinic

Plate lunch, loco moco, and malasadas

Honokaa, past Waimeaon the way to Hilo or Waipio Valley

Dysplasia: Primary HPV screening

3 screening strategies1. “Cytology”: Cytology w reflex HPV for ascus2. “Hybrid”: #1 for 25-29 yo and cotest for

>=30yo (current US strategy)3. “HPV primary” for >=25yo. Algorithm:

Neg HPVrescreen 3 yr

+16/18 colpo + other types cytology

Baseline: 10% HPV+; 6% positive cytology

ATHENA: Addressing the Need for Advanced HPV Diagnostics3 yr cohort study looking at various screening strategies. N=41K >25yo. Pap plus cobas HPV. Colpo if either abnormal. Colpo w/ biopsy at study end. Endpoints: CIN2+ detection, number screening tests and colpos

Cobas HPV: 3 separate results for hpv 16, 18 and 12 other high risk types

Primary HPV strategy had higher sensitivity than cytology and hybrid but lower specificity Increased sensitivity of primary HPV strategy due

to earlier initiation of HPV screening (25yo for primary HPV group, 30yo for hybrid group)

Primary HPV strategy had more colposcopies compared with cytology but similar to hybrid strategy

Cytology had the lowest number of screening tests followed by HPV primary then hybrid strategy

ATHENA: Addressing the Need for Advanced HPV Diagnostics3 yr cohort study looking at various screening strategies. N=41K >25yo. Pap plus cobas HPV. Colpo if either abnormal. Colpo w/ biopsy at study end. Endpoints: CIN2+ detection, number screening tests and colpos

Cobas HPV: 3 separate results for hpv 16, 18 and 12 other high risk types

A negative hrHPV test provides greater reassurance of low CIN3+ risk than a negative cytology result

Can primary hrHPV screening be considered as an alternative to current U.S. cervical cancer screening methods? Yes only for >=25yo and not yet recommended in major guidelines

How should one manage a positive hrHPV result? See algorithm

Use only the FDA approved Cobas test>=3 yrs

Not specified how, cotest?

Questions remain: primary HPV screeningAny strategy that includes HPV screening increases

the number of positive results and number of colposcopies performed. Need comparative effectiveness studies that consider

lifetime number of screening tests, colpos, follow-up visits and cost comparisons

Unclear why the recommendation to do primary HPV screening at >25yo when USPSTF recommends against any HPV testing in <30yo (“D” grade)

Long-term outcomes remain uncertain. (studies only 3-5 yrs. ATHENA only one screening round)

Given strong potential for bias due to study sponsorship by Roche, should we wait for more studies before adopting?

Role of the sponsorRoche Molecular Systems, Pleasanton, CA was involved in all aspectsof the design and conduct of the study; collection, management, analysis, and interpretation of the data. Catherine Behrens and Abha Sharma who are Roche employees were integral to the preparation of the manuscript and the sponsor reviewed the final manuscript.

snapshots

USPSTF—depression screening now recommended in all pregnant women

OCP not associated with birth defects Letrozole no better than clomid for ovulation

inductionCDC recommends test of cure for women with

Trichomonas infection Fertility drugs not associated with development of

borderline ovarian tumors but progesterone use was (RR 1.8 for any use, 2.6 for >4 cycles)

Questions?