Menopause

Definition: Loss of ovarian follicular function. Recognized after 12 months of amenorrhea.

- Ave. age 52 years.

- Premature menopause - definitive cases of menopause before age 40 yrs.

- Elevations in Follicle-stimulating hormone (FSH).

*Diagnosis is best done by menstrual calendar, not hormone measurements.

*Use low dose OCPs in healthy nonsmokers for menstrual irregularities.

*Risk of endometrial pathology is increased at menopause transition, and heavy or irregular bleeding should be evaluated.

Premature Ovarian Insufficiency:

- Primary ovarian insufficiency - transient or permanent loss of ovarian function leading to amenorrhea in women <40 yrs.

- Eval for any women who misses 3 or more consecutive cycles.

    - hCG, FSH, estradiol, prolactin, TSH. *Diagnosis is confirmed by 2 elevated FSH levels at least 1 month apart.

    - Consider Karyotype, Fragile X premutation, thyroid peroxidase antibodies, adrenal antibodies, fasting glucose, serum calciun and phosphorus.

    - Treat with estrogen if not contraindicated.

Vulvovaginal Changes(VVC):

- Symptoms include: irritation, burning, itching, discharge, postcoital bleeding and dyspareunia (Genitourinary syndrome of menopause, GSM, encompasses VVC).

   - This occurs in any age woman with low estrogen.

   - Vulvar dystrophies (lichen sclerosis, lichen planus, squamous cell hyperplasia/lichen simplex chronicus) and vulvar dysplasia or cancer may present with VVC symptoms.

- Include VVC symptoms in ROS of all peri- and postmenopausal women.

- Any white, pigmented, or thickened vulvar or vaginal lesions should be biopsied to obtain an accurate diagnosis.

- Any postmenopausal bleeding, even postcoital, requires thorough evaluation.

- Atrophy Tx:

    - Estradiol cream 0.5g qday for 1 week, then twice weekly for maintenance.

    - 0.5mg estradiol tab placed vaginally twice weekly at bedtime (if cream is not covered by insurance)

WHI:

A set of two hormone therapy trials (unopposed estrogen and continuous combined estrogen-progestin therapy versus placebo) in approx. 27,000 postmenopausal women with ave. age 63, published in 2002.

Showed adverse outcomes such as risk of CHD, stroke, VTE and breast cancer with HT.

*USPSTF completed a more recent metanalysis in 2012. Recommend against HT for prevention of chronic disease, but HT still may be used for relief of menopausal symptoms.

- Limit combined HT to 5 years due to increased breast cancer risk. Unopposed estrogen may be used longer.

• • The number of women who were diagnosed with breast cancer was slightly higher in women taking estrogen plus progestin.

  • The number of women who developed heart attacks, strokes, or blood clots in the lungs and legs was higher in women taking estrogen plus progestin.

    • Esp. in the first year - increased CHD.

  • The number of women who had hip and other fractures or colorectal cancer was lower in women taking estrogen plus progestin.

  • There were no differences in the number of women who had endometrial cancer (cancer of the lining of the uterus) or in the number of total deaths.

  • There was no observed increase in the risk of breast cancer in women taking estrogen alone versus those taking a placebo. In fact, there was a slight decrease.

  • No improvement of overall mortality on combined estrogen plus progestin.

http://my.clevelandclinic.org/health/articles/the-womens-health-initiative.

Hormonal Therapy:

- Estrogen-progesterone have higher risk of VTE than estrogen alone.

- Transdermal and local estrogen have limited effect on risk of VTE.

    - Oral estrogen "may exert a prothrombotic effect through the hepatic first passage effect and therefore increased plasma levels of Factor IX, prothrombin fragment 1þ2 APC resistance, and C-reactive protein. It has been found that oral estrogen therapy decreases levels of tissue plasminogen activator antigen and plasminogen activator inhibitor activity."

(Risk of Venous Thromboembolism Associated With Local and Systemic Use of Hormone Therapy in Peri- and Postmenopausal Women and in Relation to Type and Route of Administration. Annica Bergendal, MD, PhD; et al. Menopause. 2016;23(6):593-599.)

- Estrogen - reduction in hot flashes by 75%.

- Cancer Risk:

    - Combined = increased breast ca risk

    - Estrogen only = increased endometrial ca risk

- 300mg prometrium every night to aid with sleep disturbance/night sweats, with or without estrogen

Hormone Alternatives:

- Veozah (neurokinin 3 receptor antagonist): 45mg daily - check liver enzymes

- SSRIs, SNRIs: paroxetine, effexor, sertraline, etc...

    - Paroxetine 7.5mg/day 

- Gabapentin: 300mg TID

- Clonidine: 0.1mg/day

Non-pharmacologic Hormone Alternatives:

- Soy, red clover, black cohosh

Hypoactive Sexual Desire Disorder/Testosterone Treatment