Primary ovarian failure requires long-term treatment

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Primary ovarian failure Laurie McKenzie, MD, told attendees at the 2021 annual meeting of the American College of Obstetricians and Gynecologists.

Formerly known as primary ovarian failure, primary ovarian failure syndrome (POI) no longer refers to failure in part because of the negative connotations of the term, but mostly because it is not precisely accurate, said McKenzie, a reproductive endocrinologist. and associate professor of ob gynecologist. at the MD Anderson Cancer Center at the University of Texas with a joint appointment at Baylor College of Medicine, both in Houston.

“Many of these women, especially at the beginning of the diagnosis, may experience some intermittent ovarian function, so it may not be a complete failure of the ovaries,” McKenzie said.

Although the disease is not common, as it affects approximately 1% of the female population, “it’s the kind of thing that when a gynecologist has someone who has this visit in their office, you really need to know how to address it because these women are understandably very distressed. ” Lauren Streicher, MD, clinical professor of obstetrics and gynecology at Northwestern University, Chicago, said in an interview after attending the talk.

Women who develop PDI lose ovarian activity before the age of 40, characterized by menstrual disorders with high and low gonadotropins estradiol. Symptoms include hot flashes and night sweats characteristic of estrogen deficiency, as well as vaginal symptoms, including dyspareunia and dryness. Other symptoms may include sleep disorders, mood swings, poor concentration, stiffness, dry eyes, altered urinary frequency, low libido and lack of energy.

McKenzie urged doctors to ask women about their symptoms if they have amenorrhea due to young women primary amenorrhea they rarely experience symptoms on presentation, “implying that these symptoms are due to estrogen withdrawal rather than estrogen deficiency,” he said. The diagnosis involves confirmation of 4-6 months of amenorrhea or oligomenorrhea and two measures of elevation follicle stimulating hormone (FSH). After this work, doctors should look for the cause of the condition.

Etiology of PDI and associated conditions

McKenzie said a wide range of conditions or genetic factors can cause PDI or be more likely in patients with PDI. Many women diagnosed with PDI have chromosomal abnormalities and there is no limit to genetic testing, she said. Most of these genetic causes (94%) are X chromosome abnormalities, including Turners-associated dysmorphic features, gonadal dysgenesis, and FMR1 abnormalities. Autosomal gene mutations could also play a role in PDI.

Although women with the complete FMR1 mutation (fragile X syndrome) do not have an increased risk of PDI, people with premutation (55-200 repetitions) have a 13% -26% higher risk of developing PDI, despite that there is no increased risk of disability. Approximately 0.8% -7.5% of women with sporadic PDI and up to 13% of women with a family history of PDI have this genetic abnormality.

McKenzie said autoimmune conditions can also develop or be related to PDI, including hypothyroidism and adrenal insufficiency. Approximately 20% of adults with PDI will develop hypothyroidism, so it is reasonable to test every 1-2 years, although there are no formal guidelines for detection. In women who do not know the cause of PDI or in whom you suspect there is an immune disorder, doctors may consider detecting 21OH-Ab antibodies or adrenocorticals. Patients with a positive 21OH-Ab test or adrenocortical antibodies should be referred to an endocrinologist to test for adrenal function and rule out Addison’s disease.

Although diabetes mellitus has been linked to PDI, there is insufficient evidence to recommend the detection of diabetes in women with PDI. There are also no indications for infection screening, but infections can cause PDI. Mumps oporitis, for example, accounts for 3% to 7% of PD cases. Cancer therapy, including radiation and chemotherapy, and surgical treatment for cancer can cause PDI.

“Smoking, alcohol, nutrition, and exposure to endocrine disruptors are implicated in the influence of menopausal age, but they are not easily diagnosed causes of PDI,” McKenzie said. “Although it has not been shown to cause PDI, cigarette smoking is toxic to the ovaries and has been linked to earlier menopause.” There are many women who are unaware of the cause of PDI.

To account for all these possibilities, McKenzie described the whole diagnosis recommended by ACOG:

  • Menstrual irregularity for at least 3-4 months

  • FSH and estradiol test

  • Try hCG, TSH and prolactin

  • If the diagnosis is confirmed, test the karyotype, premutation by FMR1, adrenal antibodies, and a pelvic sonogram.

However, she added during the questions and answers after her talk, she is not sure why a sonogram is recommended or what additional information she could provide.

Long-term consequences of the PDI

McKenzie noted that one study found a 2-year reduction in life expectancy among women who developed menopause before age 40. The reduction in life expectancy related to untreated PDI is mainly due to cardiovascular disease, he said. Women who suffer from menopause between the ages of 35 and 40 have a 50% higher risk of death ischemic cardiopathy that between the ages of 49 and 51, after adjusting to other comorbidities and confusions.

“Women with primary ovarian failure should be advised on how to reduce them cardiovascular risk factors by not smoking, exercising regularly and maintaining a healthy weight, ”McKenzie said.

No intervention has been shown to increase ovarian activity

Although fertility is substantially reduced in women with PDI, it may not disappear completely. Several studies have found pregnancy rates ranging from 1.5% to 4.8%, and one study found that 25% of women with idiopathic PDI had some evidence of ovarian function. Therefore, doctors should recommend to women with PDI the use of contraceptives if they do not want to conceive. Egg donation is an option to preserve the fertility of women with PDI, but only before it is firmly established.

“No intervention has been shown to increase ovarian activity and natural conception rates,” McKenzie said.

For women who survive childhood or adolescent cancer and become pregnant, no evidence has shown an increased risk of congenital anomalies, but yes low birth weight it is elevated in infants whose mothers received anthracyclines. Treatment with anthracyclines and mediastinal radiotherapy has also been linked to cardiomyopathy and heart failure, so an echocardiogram is indicated before pregnancy in women exposed to or at high doses. cyclophosphamide.

Abdominopelvic radiotherapy, however, has been linked to poor uterine function with an increased risk of late miscarriage, prematurity, low birth weight, stillbirth, neonatal hemorrhage, and postpartum hemorrhage.

“Pregnancy in women with Turner syndrome they have a very high risk and can have a maternal mortality of up to 3.5%, ”McKenzie said, so these pregnancies require the involvement of a cardiologist.

Other sequelae of POI may include increased bone resorption, net bone loss (2% -3% per annum shortly after menopause), and reduced bone mineral density. Women should receive 1,000 mg / day of calcium and 800 IU / day of calcium vitamin D., but bone screening remains controversial in the field. Finally, providers should not ignore the psychosocial effects of IDPs, including pain, decreased self-esteem, and sadness, even more so, potentially among adolescents.

PDI treatment

PDI management involves a two-axis strategy: providing sufficient estrogen (estradiol, ethinylestradiol, or equine conjugated estrogen) to mimic normal physiology and sufficient progestogen (synthetic or progesterone) to protect the endometrium from the mitogenic effect of estrogen.

The two main options are hormone therapy and combined oral contraceptives. Hormone therapy may allow ovulation and pregnancy in some women, but combined oral contraceptives may feel less stigmatized in those who are still young, although with a potential risk of venous thromboembolism.

Continuous treatment tends to be easier and may involve advanced bleeding in younger patients; in postmenopausal women, the risk of breast cancer is higher endometrial cancer the risk is lower. Cyclic treatment mimics the normal function of the endometrium, leading to bleeding that can help some women feel more “normal” and help them know about a pregnancy. Those who want to avoid bleeding and use contraceptives can use the levonorgestrel IUD.

Streicher said in an interview: “It’s not just very important to acknowledge that [long-term consequences] in this small group of women, but the lessons learned from young women going through menopause can be absolutely extrapolated to women going through menopause at an appropriate time. “

McKenzie had no disclosures. Streicher has consulted for Astellas Pharma and Church & Dwight and has investments in InControl Medical and Sermonix Pharmaceutical.

This article originally appeared on MDedge.com, which is part of the Medscape professional network.





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