Perimenopause, menopause, and primary ovarian insufficiency: Clinical sciences

Chapters:

Watch video only

Introduction0:00–0:45

Menopause is defined as the cessation of menses due to loss of ovarian function. The diagnosis is made once menses have been absent for twelve months and, on average, occurs around age fifty-one.
However, it can occur as early as between 40 and 45 years, in which case it’s called early menopause. Moreover, if menopausal symptoms and cessation of menses occur prior to the age of 40, that’s called premature ovarian insufficiency.
Finally, perimenopause, or the menopause transition, defines the period of time between the onset of menopausal symptoms and one year after cessation of menses, regardless of age.

Focused H&P0:45–2:05

When a patient presents with a chief concern suggesting perimenopause menopause, or primary ovarian insufficiency… your first step should be a focused history and physical examination.
The history might include abnormal uterine bleeding, amenorrhea, vasomotor symptoms such as hot flashes or night sweats, vaginal or vulvar dryness and itching and dyspareunia; as well as sleep disturbances.
Other reported symptoms might include changes in mood, weight gain, headaches, decreased libido, and cognitive changes. Of note, there’s high individual variability as to how long these symptoms last, for some women lasting up to 12 years!
Now, on the physical exam, you might find evidence of vaginal and vulvar atrophy. If you see these findings, your next step is to assess the patient’s menstrual status.
Here’s a high-yield fact! Genitourinary syndrome of menopause, or GSM, refers to a group of symptoms that are related to decreased estrogen levels at the genital epithelium.
These symptoms include vaginal and vulvar dryness, burning, and irritation; dyspareunia; urinary urgency and frequency; and frequent urinary tract infections.
Let’s begin with patients who have had menstrual bleeding within the past twelve months. They might report fluctuations in bleeding patterns such as shortened cycle length, oligomenorrhea, or heavy bleeding.

Menstrual bleeding in the last 12 months2:05–3:12

Bear in mind that bleeding patterns can also be affected by hormonal medications such as oral contraceptive pills, as well as intrauterine devices, endometrial ablation procedures, and hysterectomy.
So if your patient is on hormone based medication, menopause assessment can be inconclusive. Now, in the presence of menopausal symptoms, the first step is ruling out other causes of abnormal bleeding.
So you should obtain thyroid stimulating hormone, or TSH; prolactin; human chorionic gonadotropin, or hCG;levels; and order a pelvic ultrasound.
If TSH and prolactin levels are abnormal, if hCG is positive, or if the pelvic ultrasound demonstrates abnormal findings, consider an alternative diagnosis for abnormal bleeding.

Perimenopause3:12–4:36

On the other hand, if TSH and prolactin are normal, the hCG is negative, and the ultrasound is normal, you can diagnose perimenopause.
When treating perimenopause, remember that symptoms vary in type and severity. Therefore, management is tailored to individual needs.
Counsel all patients regarding lifestyle modifications such as exercise, sleep hygiene, and stress management. Discuss expectations for future symptoms, the timeline of the menopausal transition, and the final menstrual period.
Consider hormonal management with systemic therapy such as combined oral contraceptives or progestins, which can regulate bleeding patterns and improve vasomotor symptoms.
A progestin containing IUD, on the other hand, can manage abnormal bleeding, but doesn’t address systemic symptoms. Topical vaginal estrogen therapy can be used to treat symptoms of genitourinary syndrome of menopause.
Also consider non-hormonal therapy, including selective serotonin uptake inhibitors, SSRIs, which treat hot flashes as well as symptoms of anxiety or depression.
Gabapentin can also help manage hot flashes. Finally, endometrial ablation is a surgical option to manage abnormal uterine bleeding, but it also won’t help with systemic symptoms.

Menses absent - under age 404:36–5:16

Let’s switch gears and talk about patients whose menses have been absent for more than 12 months. First, if the patient is under the age of 40, suspect primary ovarian insufficiency.
Then, obtain labs including an FSH, estradiol, TSH, prolactin, and hCG. If the FSH is less than or equal to 20 and serum estradiol levels are normal, it’s unlikely that the patient has primary ovarian insufficiency.
Your other labs might be normal, but any abnormal value can point you to an alternative diagnosis for secondary amenorrhea.
On the other hand, if FSH is greater than 20, estradiol is low, TSH and prolactin are normal, and hCG is negative, the diagnosis is primary ovarian insufficiency, or POI.

Primary ovarian insufficiency5:16–7:31

To confirm this diagnosis, repeat FSH and estradiol 4 weeks later. Management begins with counseling.
Discuss lifestyle modifications like exercise, sleep hygiene, and stress management. Depending upon the age at diagnosis, patients may need psychosocial support as they navigate issues of fertility and self-image.
Of note, some patients may ovulate after the diagnosis is made, and a small percentage of them can conceive spontaneously.
If pregnancy is undesired, contraceptive counseling is indicated.Also, when diagnosed before age 30, genetic counseling should be offered, since POI can be a feature of genetic conditions like Turner syndrome or Fragile X syndrome.
Review the increased risks of osteoporosis and cardiovascular disease caused by decreased estrogen levels. Finally, discuss the increased risk of hypothyroidism among patients with POI and recommend periodic thyroid testing.
Medical management includes systemic hormone therapy that may be given in the form of combined oral contraceptives or menopausal hormone therapy.
Systemic hormonal therapy preserves bone density, reduces the risk of cardiovascular disease, and treats vasomotor symptoms and GSM.
Topical vaginal estrogen therapy can be added for patients with persistent GSM. Finally, consider non-hormonal therapy options, such as SSRIs for vasomotor and mood symptoms, or gabapentin for vasomotor symptoms.Here’s a clinical pearl!
The three main causes of POI are genetic, like Turner syndrome or Fragile X syndrome; autoimmune, in which case it can be associated with other autoimmune conditions, like type I diabetes mellitus or autoimmune thyroid disease; and iatrogenic, such as chemotherapy-induced ovarian insufficiency.

Menses absent - 40 to 45 (Early menopause)7:31–8:23

Now let’s look at patients between the ages of 40 and 45 with no menses for 12 months. If you suspect early menopause, consider obtaining an FSH and estradiol, but note that levels fluctuate significantly in this age group, so results may be misleading or inconclusive.
Check TSH, prolactin, and hCG levels to rule out other causes of amenorrhea. If FSH is less than or equal to 20, it’s unlikely that the patient is menopausal, so consider alternative diagnoses for secondary amenorrhea.On the other hand, if FSH is greater than 20 and estradiol is low; TSH and prolactin are normal; and hCG is negative, this suggests early menopause.
Remember to repeat FSH and estradiol levels in four weeks to confirm the diagnosis. Now, let’s quickly look at how we diagnose patients over the age 45 with 12 months of amenorrhea.

Menses absent - over 45 (Menopause)8:23–9:12

In this case, suspect menopause first. You might establish a diagnosis by history and physical examination alone.
Consider a laboratory assessment if the diagnosis is unclear, or if you suspect thyroid dysfunction or pregnancy. Labs include FSH, estradiol, TSH, prolactin and hCG.
As before, with FSH less than or equal to 20 and other labs are variable, consider an alternative diagnosis for secondary amenorrhea.
However, if FSH is greater than 20, estradiol is low, TSH and prolactin are normal and hCG is negative, that confirms menopause.
Management of both menopause and early menopause requires an individualized approach that addresses the type and severity of symptoms, the patient’s desire for intervention, and the risks and benefits of treatment.

Management of early menopause and menopause9:12–11:04

Counsel all patients about lifestyle modifications and stress management. Review the risks of osteoporosis and discuss vitamin D supplementation, as well as guidelines for bone mineral density testing.
Finally, discuss the risks and benefits of systemic menopausal hormone therapy, which can be given orally or transdermally.
Remember that patients with an intact uterus should not get unopposed systemic estrogen, so include a progestin to prevent endometrial hyperplasia.
Also, consider topical vaginal estrogen therapy for the treatment of GSM. Non-hormonal treatments, such as SSRIs, gabapentin, and clonidine, can also provide symptomatic relief for many patients.
Finally, vaginal lubricants can be recommended for dryness and dyspareunia, and some patients benefit from alternative therapies such as acupuncture, reflexology, and supplements.And one last high-yield fact!
Menopausal hormone therapy is associated with an increased risk of thromboembolic disease and breast cancer. Perform a risk assessment for patients with consideration of their personal and family history.
The patient’s age is also an important factor. Younger patients are at lower risk for thromboembolic disease and breast cancer but at higher risk for the long-term effects of estrogen deficiency, such as osteoporosis and cardiovascular disease.
Of note, the route of administration also matters, with transdermal estrogen having a lower thromboembolic risk than oral regimens.Alright, as a quick recap… Menopause typically occurs around age 51; while early menopause occurs between 40 and 45; and premature ovarian failure refers to cessation of menses prior to age 40.

Review11:04–11:47

Perimenopause is the period of time between the onset of menopausal symptoms and one year after cessation of menses, regardless of age.
Now, diagnosis and management depend on the age and severity of symptoms. Treatment options include lifestyle modifications, counseling, hormone therapy, management of abnormal uterine bleeding, and non-hormonal medications such as SSRIs,