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  • Nathan Riley, MD

Obgyno Wino Podcast Episode 78 - Management of Menopausal Symptoms

“A nation that destroys its soils destroys itself. Forests are the lungs of our land, purifying the air and giving fresh strength to our people.” - Franklin Delano Roosevelt


2015 Blaye Côtes de Bordeaux from Château Cantinot



PB#141 - Published January 2014 (Reaffirmed 2018)


Five Pearls

  1. Vasomotor symptoms are most effectively managed through estrogen alone or estrogen-progesterone preparations.

  2. As with anything, treatment of menopausal symptoms should be approach through the lowest effective dose for as short a duration as possible.

  3. Paroxetine is the only non-hormone therapy approved by FDA for management of menopausal symptoms.

  4. Vulvovaginal changes that occur with menopause include loss of subcutaneous fat of the labia majora, narrowing and shortening of the vagina, and a thinning of the epithelium, all of which can cause discomfort, dryness, and fissures.

  5. Risks of HRT probably outweigh the benefits, especially in women under age 60 or less than 10 years into menopause with severe symptoms


Review of the menstrual cycle

- pre-menopause the ovaries have a large reserve of ova, which reside in follicles until it's their time to be released in hopes of meeting a sperm --> conception

- the hypothalamus secrets GnRH, which stimulates the release of FSH and LH from the anterior pituitary

- FSH stimulates the ovarian follicles to grow; as they grow, they secrete estrogen

- increasing levels of estrogen during the follicular phase of the menstrual cycle; estrogen also thickens the endometrial lining

- eventually, one follicle (or more in the case of multi-zygotic pregnancy!) dominates and the rest fall by the wayside

- this dominant follicle ruptures in response to an LH surge, which triggers the beginning of the luteal phase of the menstrual cycle

- the ovum is released in order to meet a sperm (ovulation), and the remnants of the follicle, the "corpus collosum" begins producing high levels of progesterone to support implantation of the embryo; progesterone does this by "gluing" the thickened endometrium together, supporting vascularization, and changes in the endometrial architecture

- if conception happens, the corpus collosum fades away, and trophoblasts take on the role of pregnancy-supporting progesterone production

- if conception doesn't happen, the corpus collosum fades away and progesterone levels decline abruptly --> prompting a shedding of the endometrium (menstruation), almost universally 14 days after ovulation


How this process changes at a women approach menopause

- as a women ages, her ovarian reserve diminishes, meaning less estrogen-producing follicles

- normally, this estrogen feeds back to the brain to say "hey! we are good with FSH! follicles are looking good!"

- the brain gets this feedback, and LH causes the ovary to release an egg, and the cycle continues

- but if there aren't enough follicles to release estrogen to communicate with the brain, then FSH keeps coming, LH doesn't surge, the ovary never releases an egg, and there isn't sufficient progesterone to keep the endometrium glued together

- this results in irregular bleeding patterns and even an increased risk of endometrial cancer because progesterone protects the endometrium against hyperplasia/atypia, and remember that its abrupt decrease if conception of an ovum doesn't happen results in menstruation!

- these hormonal changes in the hypothalamic-pituitary-ovarian axis result in the menstrual irregularity and eventually complete cessation of bleeding characteristic of menopause

- average age for menopause in the U.S. is 51.4


Note: Super high serum FSH levels can reflect diminishing ovarian reserve and oncoming menopause


But hormones are important for far more than menstruation!

- menstrual irregularities can begin long before menopause

- the years preceding menopause - the "start" of the menopausal change - are referred to as peri-menopause, the climacteric, or, more recently, the menopausal transition

- vasomotor symptoms ("hot flushes") and vulvar/vaginal symptoms are also common during this time


Vasomotor symptoms

- periods of 1-5 minutes of feeling "hot", especially in the neck/face/chest regions

- may also be associated with clamminess, sweating, anxiety, and sleep disruption

- 87% of women experience these symptoms daily while transitioning

- 33% experience flushes >10x daily

- years may pass before these episodes stop

- administration of estrogen seems to decrease the frequency and intensity of symptoms

- apart from hormonal changes, there also seems to relationships with serotonergic, noradrenergic, opioid, adrenal, and autonomic systems

- black women report worst symptoms; Asian women report milder symptoms

- more common in obese women

- no known associations with serious health conditions like cardiovascular health; just really annoying!


Vaginal/vulvar symptoms

- hypoestrogenic state leads to anatomic and physiologic changes to genitourinary tract

- loss of superficial epithelial cells leads to thinning of the tissue (more easily tears, bleeds, and fissures)

- vagina shortens and narrows; loss of rugae and elasticity

- loss of subcutaneous fat in the labia majora

- labia minora may fuse together

- clitoral prepuce and urethra may shrink

- loss of estrogen also leads to decrease in vaginal flora and increase in pH

- presents as dryness, discharge, itching, and dyspareunia




Pharmacologic management of vasomotor symptoms


Hormonal therapy options

- systemic estrogen-progestin or estrogen-alone therapies are the most effective (75% reduction in weekly hot flushes along with severity)

- estrogen can be administered orally, transdermally, or topically through gels/sprays

- wide range of estradiol doses have been found effective, though higher doses likely more effective (low effective dose for shortest duration possible is recommended)

- progestin can be cyclical or continuous (outside the U.S. there are also intranasal and buccal systems that work just as well)

- treatment discontinuation should be a shared decision-making process with your patient (not necessary to stop automatically at age 65)

- progestin-only methods, testosterone, or compounded bioidentical hormones don't cut it according to the available literature

- tibolone is a synthetic steroid with specific estrogenic and progestogenic effects; limited safety and efficacy data



Risk of hormonal therapies

- there's a concern for breast cancer and VTE

- per the Women's Health Initiative (WHI): after an average of 5 years of combined HRT use, there is a slightly increased risk in breast cancer, VTE, coronary heart disease, and stroke (reduced risk of fracture and colon cancer)

-it's difficult to apply the results of the WHI to younger women earlier in their menopausal transition because many women in the WHI who suffered adverse effects were well into menopause

- a reanalysis of the WHI data actually found a cardioprotective effect from HRT in women under 60 years and w/in 10 years of menopause

- then the WHI changed their minds again...and overall risks are thought to outweigh benefits

- see my show notes on episode 71 (Management of Gynecologic Issues in Women With Breast Cancer) for a full rundown of the ridiculous selective hearing that was the WHI


Non-hormonal treatment options for vasomotor symptoms

- SSRI/SNRI: they do work but not as effective as the hormonal therapies above

- side effects: dry mouth, nausea, dizziness, constipation, nervousness, somnolence, sweating, and sexual dysfunction (low likelihood at lower dose or with longer duration of therapy)

- paroxetine is the only non-hormone therapy approved by FDA for management of menopausal symptoms

Non-pharmacologic management options for vasomotor symptoms

**none approved by FDA


Phytoestrogens

- isoflavones are common in soy products

- no studies with isoflavones in isolation have demonstrated efficacy

- no known long-term adverse effects


Herbal remedies

- Chinese herbs, gingko biloba, black cohosh, ginseng and St. John's wort have all shown promise anecdotally


Chinese herbs

- dong quai (Angelica sinensis) hasn't been found to effective for vasomotor symptoms per the limited data

- dang gui bu xue tang won out over placebo for mild symptoms in one RCT

- one study found that Chinese herbal medicine in combination with acupuncture was at least as good as HRT


Black cohosh

- aka Actaea racemosa or Cimicifuga racemosa

- limited data

- possibly toxic to the liver


**Gingko biloba, ginseng, and St. John's wort haven't outperformed placebo in any "quality" trials to date. Same goes for vitamins, reflexology.


Lifestyle modifications

- avoid alcohol and caffeine

- exercise may help (especially when combined with HRT)

Management of vulvovaginal symptoms


Estrogen

- oral or vaginal administration are effective

- vaginal is preferred if vasomotor symptoms absent

- estradiol or conjugated equine estrogen can be administered as cream, tablet, or ring --> all effective

- tablets or cream therapies are induced through daily use for 1-2 weeks, followed by maintenance therapy (weekly or twice weekly) for as long as she wishes to continue

- systemic absorption with vaginal estrogen is minimal, but there remains concern about its use in women with a history of breast cancer (lacking great data)

- the official recommendation is to try non-hormonal options first in these patients

- short course hormone therapy may still be reasonable for patients with severe symptoms, but you should consult with their oncologist



Estrogen agonist/antagonists

- Raloxifene and tamoxifen haven't been found to be helpful for vasomotor symptoms or vulvovaginal symptoms (plus they carry an increased risk of endometrial hyperplasia/malignancy)

- Ospemifene is a novel agent that shows promise (effective at 60 mg/day) and does not seem to influence the endometrium significantly

- downside of ospemifene is that is may cause hot flushes (doh!), vaginal discharge, and muscle spasms


**Non-pharm agents like lubricants should also be recommended

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