Dr. Holly L. Thacker Featured in Latest Menopause e-Consult Issue

Posted on November 26, 2018

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Source: The North American Menopause Society Menopause e-Consult

The North American Menopause Society's November 2018 issue of Menopause e-Consult features expert commentary by Speaking of Women's Health Executive Director Dr. Holly L. Thacker on midlife-related clinical issues.

Case

A 44-year-old woman presents to the clinic and reports that she has been having severe hot flashes and a diminished sex drive since undergoing endometrial ablation at age 36 for abnormal uterine bleeding. The hot flashes interfere with her daytime chores and cause nighttime awakenings. She had been using testosterone pellets, prescribed elsewhere 10 months ago, for a period of 3 months with minimal relief. She also reports associated thinning of hair, vaginal discharge, and vaginal dryness but denies any vaginal bleeding or spotting. She reports dyspareunia as well and uses a nonspecific vaginal lubricant during intercourse.

Her past medical history is uneventful. She has had a benign breast lump removed and cholecystectomy in the past. She has hypertension and diabetes on her maternal and paternal sides. She is obese but normotensive, and her physical exam is otherwise unremarkable.

Given the history of endometrial ablation, it would be difficult to rule out hyperplasia without hysteroscopy-guided endometrial sampling. How and when would you determine the “start” or age of menopause, since she became amenorrheic after ablation and started having menopause symptoms at about the same time? This question becomes crucial, especially 8 to 10 years from presumed menopause, when offering these women hormone therapy (HT) versus nonhormone options.

Submitted by Pallavi Khanna, MD, NCMP, Germantown, Tennessee

Commentary by Holly L. Thacker, MD, FACP, CCD, NCMP

This case illustrates several excellent teaching points:

1. Not all women with hot flashes and amenorrhea are postmenopausal.
2. Not all dyspareunia is vulvovaginal atrophy (VVA) or the genitourinary syndrome of menopause. Conditions such as lichen sclerosis, lichen planus, vaginal intraepithelial neoplasia, infection, and vaginismus have to be considered.
3. Testosterone pellets are not FDA approved for use in women. Systemic testosterone is aromatized to estradiol, and unopposed estrogen increases the risk for endometrial hyperplasia and cancer.
4. Women who have had endometrial ablation may have amenorrhea for several years before actual menopause or the last ovulation.
5. The Study of Women’ Health Across the Nation (SWAN) has taught us that vasomotor symptoms (VMS) can start in perimenopause long before the final menstrual period, and VMS can last a long time.

I would start off by not presuming that this women became menopausal at the time her VMS started at age 36. In fact, women at early onset of perimenopause tend to have the longest duration of perimenopause, which averages 8.57 years in the youngest age-at-onset quartile.

Thus, in women with endometrial ablations and amenorrhea, I usually obtain yearly follicle-stimulating hormone (FSH) and estradiol levels in order to “date” the onset of menopause, because we know that there are critical windows that affect the risk-benefit equation of HT.

Furthermore, in SWAN, we learned that women who were premenopausal or early perimenopausal when they first reported frequent VMS had the longest total duration of symptoms (median, 11.8 y) and postmenopausal persistence in contrast with women who were postmenopausal at the onset of VMS who had the shortest duration of VMS duration.2

In addition, black women, who reported the longest duration of VMS and additional factors related to longer duration of VMS, were a younger age (such as in this case), had a lower educational level, had greater perceived stress levels, and had high levels of depression and anxiety, highlighting the need to assess for mental health issues in women suffering with VMS.

We are told that this woman’s physical exam, save for obesity, is unremarkable. If she doesn’t have VVA or lichen sclerosis or other vulvovaginal abnormalities, it is possible she is still premenopausal or has received enough systemic testosterone that aromatized to estradiol to treat her atrophy.

I would first obtain FSH, estradiol, free testosterone, and DHEA levels. If indeed she is still premenopausal or perimenopausal, I would prescribe continuous contraceptive doses of hormones with a drospirenone-based therapy for the hair thinning. It is important to note that endometrial ablation is not a contraceptive therapy.

If she is menopausal, I would offer her HT. If mood and hair thinning were major concerns and/or her androgens are elevated, I would offer oral therapy unless there is a risk for venous thromboembolism.

We know that standard estrogen-progesterone therapy is not always ideal because of adverse events such as uterine bleeding and breast tenderness. Given her history of endometrial ablation, I would favor a so-called “designer estrogen” such as Duavee, a combination of 0.45 mg oral estrogen with 20 mg bazedoxifene.

I would not cycle her or separate the estrogen and progesterone/progestin component. If she preferred a nonoral option or she was at a higher risk for thrombosis or had elevated triglycerides, a combination estrogenprogestin patch (weekly ClimaraPro 0.045 mg estradiol plus 0.015 mg levonorgestrel or twice weekly Combipatch 0.05 mg estradiol with norethindrone acetate 0.14 mg or 0.25 mg) could be used. Oral HT will elevate sexbinding globulin hormone levels, thus lowering free testosterone levels, which will likely help her skin and hair.

As far as the reduced libido, I would assess for secondary causes versus primary hypoactive sexual desire disorder (HSDD) before considering the pros and cons of prescribing flibanserin. I would first treat her symptoms of vaginal dryness with vaginal dehydroepiandrosterone (DHEA).

Since the seminal publication of Labrie and colleagues in 2009, I have prescribed compounded vaginal DHEA until it became commercially available in 2016 in the form of Intrarosa (prasterone) 0.05%. Because there are no aromatase enzymes in the endometrium, vaginal DHEA will not stimulate the endometrium in women as higher doses of vaginal estrogen could.

Given her obesity, her endometrial ablation, and her prior unregulated, unapproved testosterone pellets, avoiding extra estrogenic stimulation to her endometrium is very important, especially given assessing postmenopause bleeding, if it occurs, will be more challenging given the scarring from the endometrial ablation.

I also would provide her with easy-to-read information on menopause, perimenopause, female sexual function, and other common midlife concerns and monitor her blood pressure, weight, and symptom response within 3 months.

References

1. Paramsothy P, Harlow SD, Nan B, et al. Duration of the menopausal transition is longer in women with young age at onset: the multiethnic Study of Women’s Health Across the Nation. Menopause. 2017;24(2): 142-149.
2. Avis NE, Crawford SL, Greendale G, et al; Study of Women’s Health Across the Nation. Duration of menopausal vasomotor symptoms over the menopause transition. JAMA Intern Med. 2015;175(4):531-539.
3. Hirsch HD, Shih E, Thacker HL. ERAAs for menopause treatment: welcome the “designer estrogens.” Cleve Clin J Med. 2017;84(6):463-470.
4. Thacker HL. Taking sides: should ob/gyns prescribe flibanserin for their patients? Contemporary OB/GYN. August 2016:24-36.
5. Labrie F, Archer D, Bouchard C, et al. Effect of intravaginal dehydroepiandrosterone (Prasterone) on libido and sexual dysfunction in postmenopausal women. Menopause. 2009;16(5):923-931.

Read the issue now to gain clinical insight