Index
It is the result of a maturation process that occurs in the hypothalamic-pituitary-ovarian (HPO) axis.
It is orchestrated by a neuroendocrine cascade that ends in the ovaries.
Anovulation is the absence of ovulation produced when the ovum is not expelled by the ovary due to lack of maturation of the oocyte.
Any alteration results in a failure to release a mature egg, leading to anovulatory cycles. Anovulation can manifest in a variety of clinical presentations, from luteal insufficiency to oligomenorrhea.
Education for these patients should focus on an understanding of the underlying disorders to ensure compliance with both medical therapy and lifestyle modifications.
What Causes Anovulation?
Anovulation can be caused by a number of hormonal imbalances, although assumptions are often made that they have to do with hyperandrogenism. That’s the case with PCOS, but not all anovulation is caused by excess male hormones.
Here are some common causes of anovulation:
Age
In peri-menopause, the ovaries are shrinking and egg production decreases in frequency, but still occurs in some cycles.
Once your period has been absent for a full year and you are officially in menopause, ovulation usually stops, however some women are still able to ovulate even after menopause.
While I can’t reverse her age, I can help older ovaries function better through mitochondrial support. Once you are in full menopause, however, conception through natural methods is unlikely.
PCOS polycystic ovary syndrome
PCOS is one of the most common reasons for anovulatory cycles. In classic PCOS, higher levels of androgens or male hormones are interfering with normal development and egg release.
Restoring ovulation means correcting high levels of testosterone or DHEA by reducing insulin. I can advise on the proper diet for PCOS and how to restore normal ovulation through natural treatment.
Hypothyroid or underactive thyroid
Think of your thyroid as the accelerator for your body. A malfunctioning thyroid means that the ovaries are not receiving adequate stimulation to develop eggs.
Low thyroid function can be helped with the right nutrients (copper, zinc, selenium, tyrosine, and iodine) and, in the case of Hashimoto’s disease, moderating the immune system. I can help your thyroid work better.
High prolactin or hyperprolactinemia
High prolactin levels can inhibit ovulation. Prolactin increases during breastfeeding, which can inhibit fertility during breastfeeding. Prolactin does not always inhibit ovulation, so breastfeeding is not a reliable means of birth control.
Prolactin blood levels also rise due to stress. Stress reduction can help lower prolactin levels and allow normal ovulation. Herbs and vitamin B6 can also help reduce excessive prolactin levels.
Low estrogen (estradiol)
The estrogen is necessary to mature follicles and produce healthy eggs. Low levels of estrogen cause the eggs not to mature enough to be released.
Supporting my endocrine system can help the ovaries, adrenal glands, pituitary, and thyroid perform optimally for healthy estrogen production.
What are the symptoms of not ovulating?
How to know if you are not ovulating:
Irregular periods
The normal cycle of rising and falling estrogen and progesterone that accompanies ovulation is what signals your body when it’s time to have your period. If an egg is not released, your body will not receive the proper signals to menstruate.
Lack of a biphasic pattern on your basal body temperature graph
If you don’t see 2 weeks of well-defined lower temperatures, followed by 2 weeks of higher temperatures of about 0.5 degrees Celsius on the BBT log, you may not be ovulating.
Excessive or prolonged menstrual bleeding
Progesterone production after ovulation helps prevent a thick uterine lining. A thicker lining means more menstrual bleeding.
Severe menstrual cramps
If you don’t ovulate and release progesterone, you may have worse menstrual cramps. Progesterone acts as a muscle relaxant to prevent cramps.
Sterility
If you don’t ovulate, you obviously can’t conceive.
Pathophysiology
To understand anovulation, you must first understand what happens during a normal ovulation cycle. In normal physiology, ovulation depends on the presence of a functioning hypothalamic-pituitary-ovarian (HPO) axis.
The arcuate nucleus within the hypothalamus is made up of a collection of neurons and, when stimulated, releases GnRH into the portal vessels of the pituitary stalk in a pulsatile fashion. GnRH stimulates receptors in the anterior pituitary gland to produce and secrete both LH and FSH.
In women, FSH induces the maturation of ovarian follicles and the eventual production of estrogen, while LH modulates androgen secretion from ovarian theca cells. Estrogen, in turn, produces negative feedback on the pituitary gland.
As the follicle grows through the accumulation of follicular fluid, the granulosa cell cohort acquires the receptors necessary to respond to LH with increased formation of cyclic adenosine monophosphate (cAMP).
During the middle cycle, circulating estrogen levels reach a concentration that causes a positive feedback action on LH secretion.
This is called the LH surge. Generally speaking, approximately 16-24 hours after the LH surge, ovulation occurs with the extrusion of a mature oocyte from the follicle of Graaf and the formation of the corpus luteum.
These events are the culmination of a well-coordinated interaction between hormones and their appropriate receptors and proteolytic enzymes and prostaglandins that act in concert with each other, all directed by the HPO axis.
The system is so sensitive that even the slightest alteration in any of these factors can disrupt its fluidity and lead to anovulation.
When problems arise at any of the many different levels involved in the normal menstrual cycle, it is sometimes helpful to separate the levels by organ system.
The hypothalamus and anterior pituitary can be considered neuroendocrine components due to their proximity to each other, while the ovaries are a separate compartment. The third aspect that can be faulty is the signaling process that occurs between these 2 areas.
The initial stimulus should come from the hypothalamus in the form of gonadotropin-releasing hormone (GnRH); this decapeptide must be secreted in a pulsatile manner within a critical range.
For example, sexual maturity is not reached until the start of regular ovulatory cycles, which can take months or years. This maturation process is orchestrated by a neuroendocrine cascade and modified by autocrine and paracrine events in the ovaries, in which GnRH is the main mediator.
How polycystic ovary syndrome (PCOS) is associated with anovulatory cycles has not been fully clarified. Two associations with this disease entity are theorized to be at least somewhat responsible for its development.
The first is the persistent elevation of LH levels in these patients; the second is the apparent arrest of antral follicle development at the 5–10 mm stage and the consequent failure to enter the preovulatory phase of the cycle.
This evidence indicates that the disturbance is primarily a central defect that initiates the cascade of events that lead to its appearance.
Similarly, any condition, whether primary or secondary, that results in persistent elevation or insufficient achievement of estrogen levels can inhibit ovulation through a disruption of the mechanisms that induce the LH surge.
To achieve the corresponding changes within the cycle, estradiol levels must rise and fall appropriately.
epidemiology
Frequency
Almost all women experience anovulatory cycles at some point in their reproductive lives. However, trying to determine the frequency of chronic anovulation in the general population is quite difficult due to lack of information.
Estimates of chronic anovulation rates range from 6% to 15% of women during the reproductive years.
Interestingly, one article presented a certain subset of the population that was at increased risk for anovulatory disorders.
This article states that reproductive endocrine disorders, such as PCOS, hypothalamic amenorrhea, premature menopause, and hyperprolactinemia, are more common in women with epilepsy than in the general female population.
The article explains in more detail the frequency of PCOS in patients suffering from epilepsy regardless of the use of antiepileptic therapy.
The risk of developing PCOS during treatment with valproate (VPA) appears to be higher in women with epilepsy than in women with bipolar disorders; this could be due to underlying neuroendocrine dysfunction.
Gynecologists should be aware of the possibility that PCOS may be related to the use of VPA in this patient population, and the risks and benefits of this treatment should be weighed in the presence of PCOS.
Mortality morbidity
The prognosis is generally favorable with adequate and timely treatment.
Morbidities associated with chronic anovulation include:
- Hyperinsulinemia .
- Insulin resistance
- Early onset of type 2 diabetes mellitus.
- Dislipidemia.
- Cardiovascular disease
- Hypertension.
- Infertility
- Hiperplasia endometrial.
- Endometrial cancer
Complications
Complications of anovulation include the following:
- Hiperplasia endometrial.
- Insulin resistance or type 2 diabetes mellitus.
- Cardiovascular disease
- Venous thromboembolism secondary to estrogen therapy.
- Electrolyte disorders (anorexia nervosa).
- Arrhythmias (anorexia nervosa).
- Complications of pregnancy.
Women with PCOS who conceive are at increased risk for gestational diabetes, preeclampsia, cesarean delivery, and preterm and postpartum delivery.
Their newborns are at increased risk of being large for gestational age, but they are not at increased risk of stillbirth or neonatal death.
Anovulation occurs only in women of reproductive age.
Anovulation is physiological at the extremes of reproductive age. During menarche, the absence of ovulation is due to the immaturity of the HPO axis, leading to uncoordinated GnRH secretion (pulsatility).
During perimenopause, ovarian factors and dysregulation of feedback mechanisms are responsible.
When anovulation occurs outside the perimenarchal or perimenopausal years, extrinsic and intrinsic causes must be excluded.
Diagnosis of anovulation
Your doctor will ask you about your menstrual cycles. If you report irregular or absent cycles, ovulatory dysfunction will be suspected. Your doctor may also ask you to track your basal body temperature at home for a few months.
Then your doctor will order a blood test to check hormone levels. One of those tests could include a progesterone blood test on day 21.
After ovulation, progesterone levels increase. If your progesterone levels are not increasing, you are probably not ovulating. Your doctor may also order an ultrasound. The ultrasound will check the shape and size of the uterus and ovaries, and will also look to see if your ovaries are polycystic, which is a symptom of PCOS.
Ultrasound can also be used to track follicle development and ovulation, although this is not commonly done. In this case, you may have multiple ultrasounds over a one to two week period.
Treatment of anovulation
Treatment will depend on the cause of the anovulation. Some cases of anovulation can be treated by lifestyle or diet changes.
If low body weight or extreme exercise is the cause of anovulation, gaining weight or decreasing your exercise routine may be enough to restart ovulation. The same goes for obesity. If you are overweight, losing even 10 percent of your current weight may be enough to restart ovulation.
The most common treatment for anovulation is fertility drugs. Clomid is generally the first proven fertility drug. If Clomid doesn’t work, there are other fertility treatments to try.
Clomid can trigger ovulation in 80 percent of anovulatory women, and help about 45 percent to get pregnant within six months of treatment.
For women with PCOS, insulin-sensitizing medications like metformin can help a woman start ovulating again. It takes six months of treatment before you know if metformin will work.
Afterward, try taking a pregnancy test. If metformin alone does not help, combined use of fertility drugs has been shown to increase the chance of success in women who do not ovulate with fertility drugs alone.
The cancer drug letrozole (Femara) may be more successful in triggering ovulation in women with PCOS.
If the cause of anovulation is premature ovarian failure or low ovarian reserve, fertility drugs are less likely to work.
But that doesn’t mean that you can’t get pregnant with your own eggs. Some women will not be able to conceive with their own eggs and may require IVF treatment with an egg donor.
