Higher Education Presentation

Perimenpause also known as the menopause transition, it is the transitional time between reproductive years and the onset of full menopause defined by the 12 months of cessation of menses. Symptoms and ages vary greatly during the menopause transition making it challenging for both diaganosis and treatment.

What is Perimenopause?

Transition to menopause

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Stages of menopause and how to treat it

Take a guess? What's the average of age of menopause? And how long is the perimenopause transition?

Objectives

Stages of the Menopause Tranistion

Symptoms of menopause

Treatment of menopause

Stages of the menopause transition

STage -3-"Late reproductive Stage"

• Late reproductive stage is when declines in ovarian reserves begins prior to overt changes in the menstrual cycle. Hormonal changes compensate for diminishing follicle counts to maintain regular ovulatory cycling.
• The earliest hormonal changes are a decrease in the ovarian production of inhibin which is responsible for restraining pituitary follicle stimulating (FSH) secretion.
• Decreased inhibin B leading to increased FSH, variable estrodial levels and decreased lutial phase progesterone.

• Changes are suble and inconsistent at this stage varying cycle to cycle, likely related to size of the follicle pool each month.
• Menstraul cycles may be normal or slightly irregular
• Symptoms can vary

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• 7 day difference in cycle length of consecutive menstrual cycles-however if not tracking a missed cycle is often one of the first signs.

• Continued depletion of ovarian folicles
• Increased cycle irregularities.
• Continued decrease in inhibin B, increase in FSH, estrodiol levels maintain or sometimes in increased due to elevated FSH stimulating the remaining follicles. But estrodiol becomes more variable as the transition progresses.
• Decreased luteal phase progesterone-Due to reduced luteal function, leading to more frequent anovulatory cycles.

The early menopausal transition

Interactivity

Creativity

Animation

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Stage -2

Anovulatory cycles having a varying underlying hormonal patterns, classified as:a. Normal rise in follicular phase estrogen and normal surge of LH, but lack of rise in luteal Pdg indicating ovulatory failureb.Normal rise in follicular phase estrogen estrolgen bur failure of LH surge, indicating hypythalamic-pituitary inssensivty ot estronen positive feedbackc. No rise in estrogen and no LH surge, though LH is elevated above basal levels despite premenopausal estrogen levels, believed to be due to hypothalamic-pituitary insensitivity to estogen negative feedback. Note: There are substantial variability of these cycle types across women with little predictibilty. And that ovulatory cycles can still occur in the late menopausal transition and fertility windows still can occur!

Stage -1, The late menopause transition

• Interval of amenorrhea ≥60 days.
• At this stage compensatory mechanisms start to fail
• FSH levels are more consistently elevated
• Estrogen levels fluctuate but are more consistently low.
• Prenanediol glucuronide (Pdg) continues to decline and cycles are less likely to demonstrate evidence of luteal activity (ELA) (i.e. anovulatory) and become longer in length.

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Early post menopause

• Now officially entering the early postmenopausal stage.
• When 12 months have passed since your last menses often termed final menstrual period (FNP)
• Ovarian reserve undetectable
• FSH contues to rise wile estrogen continues to fall until they stabilize about 2 years after FNP.

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symptoms of menopause

Now that we know about the wild hormonal changes what does this due to a woman's body during the menopausal tranistion????

Common symptoms

Some of the most common symtoms experienced during perimenopause!

Depression and anxiety.

Vasomotor symptoms

Sleep disturbances

Sexual distrubances and decreased libido

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Other SYMPTOMS

The symptoms of the menopause transition can vary greatly some things are....

• Cognitive Changes-Women often report "brain fog"
• Fatigue
• Joint pain and stiffness
• Headaches
• Weight gain including changes in body composisition including increase in central fat accumulation.
• Bone loss-Estrogen is a potent antiresportive agent at bone level thus making the hypoestrogenism of menpause an increased period increased rate of bone resortion. Estrogen promotes osteoblasts and increases calcium absorption from the instestines. Rates of bone loss increase dramatically starting one year before the FMP and persists up to 3 years with rates of bones loss as high as 5% per year, then slows again.

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A little clip from one of the menopause pioneers!

• Vasomotor symptoms can be disruptive and

affect quality of life and accounts for 1.5 million outpatient visits per year and $330 million in annual US health care costs wehn left untreated.

• Genitourinary syndrome of menopause affects up to 50% of women worldwide and unlike VSM symptoms it is progressive without treatment.

Goals of Treatment?

Treat the symptoms! But why???

Non-Hormonal Medications

Diagnosis and treatment...

Treatment of the menopausal transition is symptoms management. However, it is not a one size fits all approach. After a good history, physical exam, only sometimes laboratory studies, and bone density assessment, engage in a shared descision making discussion about treatment options including hormonal and non-hormonal treatment options considering personalized risk vs benefits for the patient.

Hormone Therapy

Lifestyle and Behavioral interventions

Management of Genitourinary symptoms

Vaginal estrogen Non-hormonal Vaginal moisterizers

SSRI Gabapentin Clonidine

• Estrogen Therapy
• Combined Therapy

Cognitive Behavioral Therapy Clinical Hypnosis

https://www-aafp-org.ucsf.idm.oclc.org/pubs/afp/issues/2023/0700/menopausal-symptoms.html

A great algorithm from the AAFP.

Note: The decision to initiate HT is challenging. Careful shared decision making must weigh all benefits vs risks.

What are the known benefits and harms of hormone therapy

• Estrogen is effective in treating VMS symptoms
• Unopposed estrogen is known to increase risk of endometrial cancer and must be administered with progesterone
• Estrogen-only hormone therapy may reduce breast cancer risk in those with a uterus
• Estrogen-progesterone hormone therapy may increase the risk in those with a uterus.
• Consensus guidelines support hormone therapy to women younger than 60 years of age within 10 years of symptom onset, do not have contridiciations for HT, and desire it for treatment of VSM.
• HT in patients older than 60 may be initiated cautiously with risk-benefit analysis.

Hormone Therapy

• Dosing should always be individually adjusted to the losest effective dose for the shortest duration
• Add progestin for the final 10-14 days of cycle for 28-30 day cycle if patient has intact uterus
• Estrogen is available in oral, transdermal, and vaginal forms. See tables to the left for formulations and dosing from AAFP
• Levonorgesterel-releasing intrauterin systyme in used off-label for endometrial protection
• Observational studies suggest transdermal estrogen-containing HT does not increase the risk of VTE compared with oral estrogen.

Types of HOrmone Therapy

• For patients with contraindications to hormone therapy SSRIs, SNRIs are shown to be effective in VMS symptoms.
• New FDA approved med Fezolinetant a neurokin 3 receptor antagonist reduces VMS comparted to placebo
• Gabapentin reduces frequency of hot flashes however less effective that estrogen and adverse effects were significant.
• Clodinidne shown effectiveness however sdied effects of dry mouth, insomnia, and drowsiness were common adverse effects.

Nonhormonal pharmacologic treaments effective for vasomotor symptoms

Symptoms include vulvovaginal dryness, itching, irritation, dyspareunia, dysuria, urinary frequency and urgency, nocturia, and recurrent UTIs.

Management of Genitourinary syndrome of natural menopause

Conclusions

Shared Decision making with patient.Benefits vs risks!

Start treatment and monitor symptoms and adverse effects

Remember to use the lowest effective dose for the shortest duration of time when using HT

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JENNIFER G. CHANG, MD, MEGHAN N. LEWIS, MD, AND MAGGIE C. WERTZ, MD. (2024). Shibboleth Authentication Request. Oclc.org. https://www-aafp-org.ucsf.idm.oclc.org/pubs/afp/issues/2023/0700/menopausal-symptoms.html Panay, N., Ang, S. B., Cheshire, R., Goldstein, S. R., Maki, P., & Nappi, R. E. (2024). Menopause and MHT in 2024: addressing the key controversies – an International Menopause Society White Paper. Climacteric, 27(5), 441–457. https://doi.org/10.1080/13697137.2024.2394950 Santoro, N., Roeca, C., Peters, B. A., & Neal-Perry, G. (2020). The Menopause Transition: Signs, Symptoms, and Management Options. The Journal of Clinical Endocrinology & Metabolism, 106(1), 1–15. https://doi.org/10.1210/clinem/dgaa764 Susan Ruth Davis, Taylor, S. L., Chandima Hemachandra, Magraith, K., Ebeling, P. R., Jane, F., & Islam, R. M. (2023). The 2023 Practitioner’s Toolkit for Managing Menopause. Climacteric, 1–20. https://doi.org/10.1080/13697137.2023.2258783

References

• Nearly 40% of women report sleep disturbances during the menopause transition
• Might be related to noctural VSM (night sweats)
• Might be related to increased anxiety and depression
• Etiology unclear but still a common!

• Mood changes marked by increased anxiety and depression are common
• Women with preexisiting depression are at greater risk of developing depression, there is a 16% prevalence of new onset depression and/or anxiety.
• Hormone changes and neurosteroids are believed to contribute dysregulation of the gamma amino butyric acid (GABA) balance between GABA-A and GABA-B, increasing vulnerability to depression.

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Globally the average age of menopause is 49-52 years of age. But perimenpause or the menopause transisiton can last up to decade for some women!

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• Hot flashes/flushes and night sweats affect most women caused by rapid rise in temperature with vasodilation.
• On average lasts 4-5 years but for nearly 25% of women can go on for 10 years
• Due to narrowing of hypothalamic thermoregulatory system in response to estrogen deprivation

• Decreased sexual desire occurs in 10% of women
• Genitourinary symptoms of menopause (GSM) include changes to the lower genital tract that occur in response to estrogen deprovation
• Symtoms of GSM include: atrophy of vulva and vagina, vaginal dryness, vaginal narrowing and shortening uterine prolopse and urinary incontinence. These changes can cause dyspareunia.
• .Estrogen deprivation reduces blood flow to the vagina, reducing vaginal secretions, increasing pH, and decreasing surface epithelium.
• Estrogen replacement shown to alleviate most GSM symptoms except incontinence.

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