Reduce morbidity, mortality with hormone therapy for premature menopause

Key takeaways:

• Any hormone therapy risks seen with natural menopause do not apply to women with premature menopause.
• Treat women with estrogen even if they do not have symptoms of hypoestrogenism.

PHILADELPHIA — Hormone therapy for women with premature menopause is underutilized due to fear of adverse effects; however, any risks observed with HT after natural menopause are not applicable to young women, according to a speaker.

Premature menopause, defined as occurrence before age 40 years, can have a profound psychological impact in young women, particularly if fertility is desired, Ekta Kapoor, MBBS, FACP, MSCP, associate professor of medicine at Mayo Clinic in Rochester, Minnesota, said during a plenary presentation at the Annual Meeting of The Menopause Society.

Premature estrogen loss, which is estimated to occur in about 3% of women, increases risk for osteoporosis, cardiovascular disease and cognitive decline. Women may also present with menopause symptoms such as hot flashes, sleep disturbances, mood changes and anxiety. In addition to spontaneous premature menopause, iatrogenic causes include pelvic surgeries such as bilateral oophorectomy, or radiation and chemotherapy.

Unless there is a true contraindication, estrogen replacement is recommended for restoration of the hormonal milieu to that of a premenopausal woman, even in the absence of symptoms of estrogen deficiency, Kapoor said.

“If a woman is done with childbearing, do we have to worry about loss of estrogen in this young person?” Kapoor said. “The answer is a resounding ‘Yes.’ This represents the loss of a female hormone that should be flowing through her veins at that age and she has lost it prior to when she should have if things followed their natural course. This is an endocrine deficiency state, and that is how it has to be treated.”

Importance of estrogen therapy

For women with such an endocrine deficiency, estrogen is truly hormone replacement therapy, akin to thyroid hormone replacement in hypothyroidism, Kapoor said. Additionally, risk-benefit discussions related to CVD also do not apply to women with premature menopause.

“I like to repeat this, because patients will often be told by their clinicians, ‘Your risk for breast cancer goes up by being on HT; you’re not having menopause symptoms so maybe we can get you off HT.’ Not true. The goal here is not just symptom management. The goal is to reduce the morbidity and mortality associated with premature estrogen deprivation.”

Randomized controlled trial data informing HT decision-making in premature menopause are sparse, and specific consensus guidelines are lacking, Kapoor said. Experts recommend use of HT at least until the age of natural menopause, with the possibility of longer use as dictated by symptoms and risk-benefit considerations, as well as use of higher doses of estrogen to approximate premenopause hormone levels. This can include an estradiol patch delivering 100 µg per day or oral estradiol 2 mg per day or equivalent doses of other forms of estrogen.

“Our goal is to treat these women with high doses because the goal is replacement,” Kapoor said. “Remember, you want to be creating a premenopausal hormonal milieu.”

Long-term studies on the appropriate progestogen regimen for endometrial protection in women on high doses of estrogen are not available, but the general principle is to use higher doses of progestogens, Kapoor said.

Establishing a diagnosis

Women with spontaneous premature menopause require a thorough history and physical examination and laboratory evaluation for establishing the diagnosis and ascertaining the etiology of menopause. Initial laboratory testing includes a serum pregnancy test, follicle-stimulating hormone (FSH), thyroid-stimulating hormone and prolactin levels. If FSH level is elevated, testing should be repeated in 4 to 6 weeks. A persistently elevated FSH of greater than 40 IU/L confirms the diagnosis of ovarian insufficiency, although some guidelines use lower thresholds, Kapoor said.

“For a lot of women experiencing spontaneous premature ovarian insufficiency, these symptoms can be intermittent [and] fluctuating a great deal,” Kapoor said. “This causes a delay in diagnosis. Many times, what these patients will tell you is they have gone months or years and seen multiple providers before they received a diagnosis.”

Kapoor said genetic testing should be offered to all women, particularly those with a family history of ovarian insufficiency and those aged younger than 30 years at the time of symptom onset.

“It is important to recognize that a lot of the women who we think have idiopathic [premature menopause] in fact have unidentified genetic conditions that we don’t yet know about,” Kapoor said.

Kapoor recommended screening for common autoimmune associations, particularly adrenal insufficiency, Hashimoto’s thyroiditis and type 1 diabetes. Ovarian antibody testing is not indicated because of poor sensitivity and specificity. Kapoor also recommended a baseline bone density analysis.

In addition to HT, management goals should include counseling and psychological support; symptom control; assistance with fertility, if desired; and reduction in long-term health risks by optimizing CV risk factors. Patients who desire childbearing should be referred to a reproductive endocrinologist.

Testosterone therapy may be a consideration in those with hypoactive sexual desire disorder, particularly after bilateral oophorectomy, Kapoor said.

“You have two goals of treatment. One is to prevent the morbidity and mortality associated with estrogen deprivation and [the other is] symptom control,” Kapoor said.