update: women’s health issuesupdate: women’s health issues objectives update the new definition...

UPDATE: Women’s Health Issues

Renee B. Alexis, MD, MBA, MPH, FACOG

Associate Professor Department of OBGYN

Kiran C. Patel College of Osteopathic Medicine

Disclosure of Conflicts of

Interest

I have no financial relationships

to disclose

UPDATE: Women’s Health

Issues

Focus: Hormone Replacement Therapy

Today

Polycystic Ovarian Disease –

Diagnosis and management

UPDATE: Women’s Health

Issues

Objectives

Update the new definition of PCOS

Review options for treatment of

patients with PCOS

Review the findings of long term

follow-up of the WHI study from 2002

Discuss new management options in

treating menopausal symptoms

Polycystic Ovarian Disease

Definition:

Traditional NIH (1990)

Clinical or biochemical hyperandrogenism

Ovulatory dysfunction

Exclusion of other androgen excess disorders

Rotterdam Consensus (2003): 2 of the following

Clinical or biochemical hyperandrogenism

Ovulatory dysfunction

Polycystic ovaries on ultrasonography

Exclusion of other androgen excess disorders

Different for adolescents


Androgen Excess and PCOS Society

Required androgen excess Plus

Ovulatory dysfunction or PCOS ovaries or both


UPDATE: Defining and diagnosing PCOS

In 2012 NIH sponsored evidence based workshop

Outcome:

Use the Rotterdam 2003 criteria for diagnosing PCOS

Specify Phenotype

Recommended renaming the disease given PCO are not a necessary finding for diagnosis

Prevalence of PCOS increased up to 20.9%

PCOS Phenotypes


UPDATE : Phenotypes and Disease Risk

Women with ovulatory dysfunction and PCO without excess

androgens have the lowest risk for diabetes mellitus

Therefore important to record phenotype for clinical care

UPDATE: Insulin resistance/Diabetes and PCOS

Measuring insulin levels not necessary for diagnosing or

management of PCOS

Fasting blood glucose inadequate for diagnosing diabetes in

women with PCOS; 2hrOGTT recommended in all women with

PCOS


UPDATE

Unlike metabolic syndrome, it is uncertain if PCOS is an

independent risk factor for CV disease

Large scale prospective trials needed to further elucidate of

CV development

Similar to diabetes risk of CV disease may be phenotype

specific


Management

Depends on clinical manifestations and desires of the patient


UPDATE: Management

Modest weight reduction 5-10% improves insulin resistance and improves reproductive features

No specific diet is better over another

Reduce caloric intake

150 min of exercise (aerobic) per week

Even prevention of additional weight gain is important

Target women with BMI >25


UPDATE: Management

Oral estrogen-progestin pills (OEP)

Reduces LH which decreases ovarian androgen production

Increased SHBG which decreases free testosterone levels

Reduced endometrial hyperplasia

Best OEP for those with acne are those with less androgenic

progestin (FDA approved: Drospirenone, desogestrel,

norgestimate and norethindrone acetate)

Contraindications to OEP

Oral progestin (norethindrone acetate 5 mg daily)

Levonorgestrel IUD


UPDATE: Management

Problem with OEP:

OEP does not improve insulin resistance or reduce fat

secretion of adipokines

OEP does not block androgen at the level of the skin

Recommendation for dual therapy

Metformin

Spironolactone


UPDATE: Management

OEP plus Metformin in women with insulin resistance

In some trials OEP and metformin 1,500mg daily led to greater increase in SHBG than OEP alone

Also weight loss and reduction of waist to hip ratio occurred only in patients with OEP plus metformin group

Consider OEP plus metformin in patients that have

BMI >30 kg/m2

Waist-to-hip ration > 0.85

Acanthosis Nigrans

History of gestational diabetes, family history

Diagnosis of metabolic syndrome


UPDATE: Management

Spironolactone with OEP for women with

hirsutism

Spironolactone adds to the effect of reduced LH

from OEP

A few small trials have demonstrated better

treatment of hirsutism with OEP plus

spironolactone vs. OEP mono-therapy


Ovulation Induction Management

Clomiphene citrate

SERM

FDA approved for ovulation induction

Resistance can be observed

Letrozole

aromatase inhibitor

not FDA approved for ovulation induction


UPDATE: Management Ovulation Induction

Progestin withdrawal not necessary before increasing clomid does; may actually reduce live births

Stepwise increase in clomid dose can reduce time to ovulation

Clomid with metformin and clomid alone have similar live birth rates but better than metformin alone

When compared to clomid, letrozole had significantly more live births

Letrozole may be the preferred ovulation induction therapy in patients with PCOS especially in those women who display resistance to clomid


UPDATE

Evaluate for emotional well being and refer for

appropriate treatment

Recognition of anxiety and depression remains

low and prevalence is high (30%)

Mood disorders may affect women with PCOS

and treatment of disease.

Hormone Replacement Therapy

The importance

31.3 million postmenopausal women by 2010

consensus

2million women per year enter menopause

Life expectancy is increasing currently 81 years

Hormone Therapy prescribed since the

1960s

Initially for menopausal symptoms

Shifted to menopause and a preventable disease


UPDATE: Terminology

Ovaries age at different rates in different women

In 2012 updated Stages of Reproductive Aging

Workshop (STRAW+10)

Divides reproductive aging into 4 stages

Reproductive stage

Menopausal transition

Early postmenopausal period

Late postmenopausal period

Characterized by menstrual cycle


1997 Postmenopausal estrogen/Progestin

Intervention Trial

Evaluated HRT and CV disease markers

Favorable effects o lipids

1998 the Heart and Estrogen/Progestin

Replacement Study

No favorable benefit of HRT in prevention of CV

disease


In 2002 Women's Health Initiative (WHI)

Estrogen plus Progestin Trial results

Stopped early 5.2 years of follow up

Increased risk of CV disease

Increased breast cancer risk

Decreased risk of colon cancer

Decreased risk of hip fracture


Women's Health Initiative (WHI) (con’t)

Estrogen alone therapy

Increased stroke and thromboembolic

events

No increase in CV disease risk

No increase in breast cancer risk

Decreased risk of hip fracture


Given that the increase in breast cancer was

seen in the EPT arm of the study there is

concern that it may very well be the type of

progestin that increase the risk of breast

cancer with systemic HT


WHI long term follow up

2013 report from WHI

Systemic HT safe to initiate women younger than

60 years of age and less than 10 year since onset

of menopause

Cumulative 18 year follow-up (both ET and EPT)

Systemic HT did not increase all cause mortality

(even with stratifying bay age)

Systemic HT did not increase cause specific

mortality

All cancer mortality

CV mortality


WHI long term follow-up (con’t)

Breast cancer mortality

EPT risk was 1.44

ET risk was 0.55


WHI in review

Generalizability is limited with use of other HT preparations

Different routes were not assessed

Different types of progestational agents were not evaluated

Many subgroups and many outcomes were evaluated in this

one study which limits interpretation of HT and cause specific

mortality.


UPDATE

The cumulative follow up of the WHI study and no

increase in all cause mortality is important for

assessing safety of systemic HT 5-7 years

North American Menopause Society (NAMS) and the

Endocrine Society agree that HT is a viable option for

treating menopausal women with moderates to

severe symptoms


UPDATE

Novel Preparations of systemic HT

FDA approved SERM Bazodoxifene with

conjugated estrogen

Reduce vasomotor symptoms of menopause

without increasing risk of endometrial cancer

No increase in myocardial infarction

thromboembolic disease


Bio identical hormones

Estrogen and progesterone that is chemicals that are compounded and is identical to those produce in the body )E2 and progesterone)

Often reported to be safer and more effective than commercial preparations

Claims of slowing the aging process

Claims that they deliver customized dose

Saliva testing is performed to evaluate circulating hormone level


UPDATE Bio Identical hormones

No research has shown that they are superior to

commercially available preparations

Has not been shown to be safer than other available

systemic HT preparations

Customized compounding may have limited quality

control untested purity and may vary from batch to

batch

Difficult to customized dose because a woman's

hormone levels vary from day to day


UPDATE Bio Identical hormones (con’t)

Saliva testing is expensive and not needed for starting

hormonal therapy

Compounded progesterone products may not result in

sufficient amount to protect the uterine lining


Determining reproductive aging is

important since it helps to make the

diagnosis of conditions and guide

treatment options


UPDATE

HT is safe to give to postmenopausal women for

moderate to severe vasomotor symptoms or

vulvo-vaginal symptoms

2012 Cochrane review of randomized double blind

placebo controlled trials of HT

Supports HT not for use to prevent CV disease or

dementia

Similar findings of WHI study including increase risk of GB

disease

Over 65 had increased risk of dementia


UPDATE (Con’t)

Characteristics to start systemic HT

Younger than 60

Less than 10 years since last menstrual period

No history of major risk factors such as CV disease, stroke, DVT/PE, breast

cancer abnormal vaginal bleeding

Lowest dose shortest amount of time

Recommended those in early or premature menopause would likely

benefit from HT until at least natural menopause age

Symptom relief

Maintain BMD

Possible reduction in risk of CV disease


Routes of administration

Oral

Transdermal

intravaginal

Options include

Systemic HT

Bazodoxifene plus estrogen therapy

Vaginal/local estrogen

Low dose paroxetine

Updates: Women's Health Issues

Conclusion

PCOS

PCOS is a dynamic disease not only in its phenotypes but also in its definition and management

PCOS impacts the health of women significantly and has a high disease burden

Define PCOS based on it phenotypes to direct appropriate treatment

Consider adding metformin and spironolactone or both to OEP to better manage patient symptoms

Letrozole is better at ovulation induction than clomid

Updates: Womens Health Issues

HRT

Systemic HT is still a safe and viable option for treatment of women who have moderate to severe menopausal symptoms

HT is should not be prescribed as a preventative medication

Evidence has shown that for women with premature menopause or menopause before age 45 y/o, systemic HT may reduce the risk of CV disease and associated morbidity and mortality

Bioidentical hormones can be expensive and have no better efficacy or safety than commercial preparations. In addition, compounded progesterone may be substandard in protecting the uterine lining

Transdermal preparations may offer lower risk of thromboembolic disease

References

1, Hoger MD, Kathleen and Vitek, Wendy. Polycystic ovarian disease. Clinical Updates in Women’s Healthcare. Volume XV, Number 4, July, 2016.

2. Shifren MD, Jan L. and Schlam Eldelman, MD, Julia. Hormone therapy and alternative therapies for menopause. Clinical Updates in Women’s Heathcare. Volume XIV, Number 4, October, 2015.

3. Barbieri, Robert. Treating Polycystic ovary syndrome: Start using dual medical therapy. OBG Management. April 2017;29(4);8-10, 12-13.

4. Kaunitz MD, Andrew. Did long term follow-up of WHI participants reveal mortality increase among women who received HT?

update: women’s health issuesupdate: women’s health issues objectives update the new definition...

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