From the Guidelines
Progesterone and prolactin levels are essential in evaluating irregular menstrual cycles, with progesterone measurement during the luteal phase and prolactin assessment in the morning while fasting being critical components of the evaluation. The role of these hormones in evaluating irregular menstrual cycles is multifaceted. Progesterone measurement during the luteal phase, typically day 21 of a 28-day cycle, helps determine if ovulation has occurred, with levels above 3-10 ng/mL indicating successful ovulation 1. Low progesterone suggests anovulation, which can cause irregular cycles.
Key Considerations for Progesterone and Prolactin Measurement
- Progesterone levels should be measured 7 days before expected menses or during the mid-luteal phase to accurately assess ovulation.
- Prolactin should be measured in the morning while fasting, as levels fluctuate throughout the day and can be affected by stress, exercise, and meals.
- Elevated prolactin levels can disrupt the hypothalamic-pituitary-ovarian axis, leading to irregular or absent periods, and may result from pituitary adenomas, medications, hypothyroidism, or stress 1.
Causes of Irregular Menstrual Cycles
- Polycystic ovary syndrome (PCOS)
- Hypothalamic amenorrhea
- Hyperprolactinemia
- Thyroid dysfunction
Evaluation and Management
When evaluating irregular cycles, these hormones should be measured alongside other tests like thyroid function, FSH, LH, and estradiol 1. The American College of Obstetricians and Gynecologists (ACOG) recommends a comprehensive evaluation, including medical history, physical examination, and selected laboratory and imaging tests, to determine the underlying cause of abnormal uterine bleeding associated with ovulatory dysfunction 1.
Recent Guidelines
According to the most recent guidelines, a single prolactin measurement taken at any time of the day is sufficient to assess hyperprolactinaemia, but serial measurements over time may be necessary to exclude the effect of stress and prolactin pulsatility 1. The diagnosis of hyperprolactinaemia requires age-specific and sex-specific prolactin reference ranges and the exclusion of confounding conditions such as hypothyroidism, renal and/or hepatic impairment, and use of medications that cause hyperprolactinaemia 1.
Clinical Implications
In clinical practice, the measurement of progesterone and prolactin levels should be tailored to the individual patient's needs, taking into account their medical history, symptoms, and physical examination findings. By prioritizing the measurement of these hormones and considering the underlying causes of irregular menstrual cycles, clinicians can provide effective evaluation and management of irregular menstrual cycles, ultimately improving patient outcomes in terms of morbidity, mortality, and quality of life.
From the FDA Drug Label
The results for the incidence of endometrial hyperplasia in women receiving up to 3 years of treatment are shown in Table 3 A comparison of the progesterone capsules plus conjugated estrogens treatment group to the conjugated estrogens only group showed a significantly lower rate of hyperplasia (6 percent combination product versus 64 percent estrogen alone) in the progesterone capsules plus conjugated estrogens treatment group throughout 36 months of treatment. Effects on secondary amenorrhea In a single-center, randomized, double-blind clinical study that included premenopausal women with secondary amenorrhea for at least 90 days, administration of 10 days of progesterone capsules therapy resulted in 80 percent of women experiencing withdrawal bleeding within 7 days of the last dose of progesterone capsules, 300 mg per day (n=20), compared to 10 percent of women experiencing withdrawal bleeding in the placebo group (n=21)
The role of progesterone levels in evaluating irregular menstrual cycles is to assess the presence of ovulation and luteal phase adequacy. Progesterone therapy can induce withdrawal bleeding in women with secondary amenorrhea, indicating the presence of a responsive endometrium. However, prolactin levels are not directly mentioned in the provided drug label. Therefore, the FDA drug label does not provide information on the role of prolactin levels in evaluating irregular menstrual cycles 2.
From the Research
Progesterone and Prolactin Levels in Evaluating Irregular Menstrual Cycles
- Progesterone levels play a significant role in evaluating irregular menstrual cycles, as they can indicate ovulation and luteal phase defects 3, 4, 5, 6.
- A single serum progesterone measurement may not be a reliable indicator of ovulation, as progesterone secretion is pulsatile throughout the human luteal phase 3.
- A random serum progesterone level of ≥5ng/ml can confirm ovulation with high specificity and sensitivity 4.
- Urine progesterone tests can also be used to confirm ovulation, with a threshold of 5μg/mL showing 100% specificity in past studies 5.
- Prolactin levels can also affect menstrual cycles, and elevated prolactin serum levels have been documented in patients with polycystic ovaries 7.
- The effect of exogenous estrogen and progesterone on the secretion of prolactin must be considered when evaluating therapeutic alternatives for dysfunctional uterine bleeding and hirsutism in patients with hyperprolactinemia and polycystic ovary syndrome (PCOS) 7.
Diagnostic Thresholds
- A serum progesterone level of ≥5ng/ml can confirm ovulation 4.
- A urine progesterone test with a threshold of 5μg/mL can confirm ovulation in 82% of cycles 5.
- A discriminatory level of 21 nmol/L for serum progesterone measurement can diagnose luteal phase defects with a sensitivity of 81% and specificity of 73% on days 25-26 of the menstrual cycle 6.