update: women’s health issuesupdate: women’s health issues objectives update the new definition...
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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
Polycystic Ovarian Disease
Androgen Excess and PCOS Society
Required androgen excess Plus
Ovulatory dysfunction or PCOS ovaries or both
Polycystic Ovarian Disease
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
Polycystic Ovarian Disease
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
Polycystic Ovarian Disease
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
Polycystic Ovarian Disease
Management
Depends on clinical manifestations and desires of the patient
Polycystic Ovarian Disease
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
Polycystic Ovarian Disease
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
Polycystic Ovarian Disease
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
Polycystic Ovarian Disease
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
Polycystic Ovarian Disease
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
Polycystic Ovarian Disease
Ovulation Induction Management
Clomiphene citrate
SERM
FDA approved for ovulation induction
Resistance can be observed
Letrozole
aromatase inhibitor
not FDA approved for ovulation induction
Polycystic Ovarian Disease
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
Polycystic Ovarian Disease
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
Hormone Replacement Therapy
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
Hormone Replacement Therapy
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
Hormone Replacement Therapy
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
Hormone Replacement Therapy
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
Hormone Replacement Therapy
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
Hormone Replacement Therapy
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
Hormone Replacement Therapy
WHI long term follow-up (con’t)
Breast cancer mortality
EPT risk was 1.44
ET risk was 0.55
Hormone Replacement Therapy
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.
Hormone Replacement Therapy
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
Hormone Replacement Therapy
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
Hormone Replacement Therapy
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
Hormone Replacement Therapy
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
Hormone Replacement Therapy
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
Hormone Replacement Therapy
Determining reproductive aging is
important since it helps to make the
diagnosis of conditions and guide
treatment options
Hormone Replacement Therapy
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
Hormone Replacement Therapy
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
Hormone Replacement Therapy
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?
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