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Evidence-based answers

These statements are intended only to provide information, not medical advice. Medical issues should be discussed with the responsible clinician who is prescribing the treatment. Treatment must be evaluated in the context of each individual’s specific situation. Following is information and evidence in medical literature. Anything read here should be discussed with an individual’s own health care team to determine if this evidence applies to your situation.

  • Published scientific evidence has demonstrated the most common problem preventing normal ovarian follicle function and ovulation in women with POI is inappropriate luteinization of growing follicles.
  • Published evidence has demonstrated the NIH P-HRT regimen suppresses serum LH levels to normal in women with POI. Published evidence has demonstrated you should be on the NIH P-HRT regimen to keep your bones healthy.
  • Theoretically, lowering the LH level in your blood should improve the chances of you ovulating by reducing the chances of the follicles becoming luteinized. This has not yet been proven by prospective study, however. As a group, women with POI should be advocating for more studies about how to improve their natural fertility.

Frequently Asked Questions

How do I prepare for a healthy pregnancy based on the best evidence?

Preconception health care focuses on the parts of health that have been shown to increase the chance of having a healthy baby. Because it differs from person to person depending on unique individual needs, it’s best to ask your healthcare provider about your unique preconception care, however you can find general CDC guidelines to get you started here.

How do women with POI who are trying to conceive (TTC) handle hormone replacement therapy (HRT)?

Here is a helpful set of steps to take:

1. Discuss getting on the National Institutes of Health physiologic HRT regimen (NIH P-HRT). This will give you regular menstrual cycles so you will know to get a pregnancy test if a cycle is late. The best evidence suggests you should not take birth control pills for your HRT. These change your cervical mucus and lining of your womb to be hostile to fertilization and implantation.

2.Because your chances to conceive are less than normal, it’s important to remember that if you do conceive, you want to maximize your chances of a healthy pregnancy. Discuss your general health with your provider and attend to the necessary recommendations for preconception health.

3.Plan to make intercourse fun, and have intercourse two or three times a week. This will assure there will always be sperm present for the occasional ovulation women with POI experience. (Published evidence suggests on average women with POI have a 50 percent chance of ovulating sometime during the next year, but you cannot tell when the ovulation will occur.)

4.Keep a menstrual calendar, and get a pregnancy test if your period is late. Set a reasonable time to try to conceive before moving on to other solutions. This is a personal decision; many women and their partners are comfortable trying to conceive for several years before looking into egg donation, adoption, or other solutions to help them expand their family.

How is P-HRT safer than the standard traditional HRT? And, what are the risks?

Women with POI are missing the main hormone messenger estradiol, which has the main function of maturing and then maintaining the reproductive system. During the menstrual cycle, increased estradiol levels permit the maturation and release of the egg, as well as the thickening of the uterus lining to allow a fertilized egg to implant.

P-HRT restores the natural levels of estradiol using the exact same hormone — that is, estradiol itself. The term “physiologic” means the estradiol is administered directly into your bloodstream, typically via a skin patch or vaginal ring, rather than through the mouth and past the liver. Estrogens taken by mouth (as in traditional HRT) expose the liver to extremely high levels of estrogen and change normal liver function in adverse ways. In short, P-HRT averts this risk. Here is the good news based on the best evidence:

• Blood clots: With P-HRT the estradiol is given by skin patch or vaginal ring, which does not increase the risk of blood clots. In contrast, taking estrogens by mouth in the form of a pill increases the risk for developing blood clots, which can be fatal if they travel to the lungs. The risk of this complication is greater for people who smoke or are obese and take traditional HRT.

Breast cancer: For women with POI, the P-HRT is not expected to increase the risk of breast cancer above normal. POI is unique in that young women are replacing the hormones their ovaries would normally be providing, which is dramatically different than older women who have normal menopause and are beyond the age of their body making the estradiol amounts found in younger women. In short, women with POI take physiologic “hormone replacement” when they use the estradiol patch or vaginal ring. Menopausal women who take estrogen and progestin replacement by mouth are not taking “hormone replacement;” indeed, these women are extending estrogen exposure beyond what takes place naturally. As such, estrogen and progestin replacement taken by mouth in menopausal women has been associated with a higher risk of breast cancer due to the longer exposure to estrogen.

• Uterine or Endometrial cancer: When taken alone, estradiol increases the risk for uterine cancer, which is why a progestogen is recommended in addition to estradiol replacement in POI. However, for women who have had their uterus removed, it is not necessary to take a progestogen.

What are treatments for POI and/or associated estradiol deficiency?

Although there’s currently no known cure for POI, there are ways to reduce symptoms and stabilize a woman’s overall health. One way to do this is through physiologic hormone replacement therapy, or P-HRT. This treatment is important for women with POI since it aims to restore the estradiol deficiency, which not only helps the ovaries function properly but also contributes to bone health, cardiovascular health, and brain health.

Other treatment recommendations include the assurance of adequate calcium and vitamin D intake to further support skeletal health, as well as regular exercise and good dietary habits to maintain a healthy weight.

How do I find a provider willing to help me with POI?

At My 28 Days, we believe women with POI need accurate, credible information so they can take a proactive, preventive approach to menstrual health. It’s important to note the goal of preventive medicine is the absence of disease — either by preventing the occurrence of a disease or by halting it at its onset and thereby reducing complications. As part of this proactive approach — and more so because POI is a rare and often misunderstood condition — we recommend women with POI symptoms both educate and advocate for themselves and share the evidence-based research we present here with their practitioners. Because research has demonstrated POI is associated with a shorter life expectancy if not managed appropriately (a result of the long-term effects of estradiol deficiency), it’s important to seek the necessary care with some urgency.

All things considered, fertility specialists are generally not adept at a preventative medicine approach, as this is not the focus of their training and experience. Most medical schools, however, have a department of family and preventive medicine, which is a good place for women with POI to find a qualified clinician. At My 28 Days, it’s our goal to make resources regarding POI more available to women so they can better understand their treatment options. Still, women need to be prepared to educate the clinician about their needs and about the disorder in general. Preventive medicine clinicians are generally very open to learning about new evidence in their field. Our resources section may help offer some guidance as you explain your concerns with your clinician.

What are some symptoms of primary ovarian insufficiency and estradiol deficiency?

One of the early symptoms of the onset of POI is irregular or missed periods. As the disorder progresses and the hormonal deficiency worsens, other symptoms that resemble menopause may appear, including:

• Hot flashes
• Night sweats
• Mood instability and irritability
• Poor concentration and/or “brain fog”
• Decreased libido
• Painful intercourse
• Vaginal dryness
• Infertility

In addition, the hormonal deficiency caused by POI can upset other normal operations and processes within the body, which can often result in other conditions, such as:

Osteoporosis. Although the hormone message estradiol is associated with reproductive organs, it also affects skeletal health and bone density. Without sufficient levels of estradiol, bones can become weak, brittle, and less dense, increasing risk for fracture.

Heart disease. The lower levels of estradiol in the body are associated with increased risk of hardened arteries, also called atherosclerosis.

Anxiety and depression. Rather than just short-term irritability or moodiness, POI can be associated with more longer-term mental health issues, even triggering the onset of depression and anxiety where there was no major problem before.

Dry eye syndrome. and other issues with the surface of the eye. Without treatment, severe dry eye can cause permanent vision damage.

Menstrual and Ovarian Health

Follow the Evidence

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