Thyroid Awareness Month
Hormonal Disorders and Uterine Bleeding: A Review of Research
By: Liz McAuliff
Director’s Note: January is Thyroid Awareness Month, and this week we feature research about the impact of thyroid disorders on patients with abnormal uterine bleeding (AUB). Liz McAuliff, a former FACTS elective participant, summarized the study titled, “Prevalence of hyperprolactinemia and thyroid disorders among patients with abnormal uterine bleeding.”  Published in the International Journal of Gynecology & Obstetrics in 2015 by Abdel et al, the study discusses implications of abnormal thyroid and prolactin levels and the prevalence of hyperprolactinemia among women with AUB. In her summary, McAuliff mentions charting as a cost-effective means to gain insight into the possible etiology of AUB in an individual patient. Earlier identification of AUB with the use of fertility awareness-based methods (FABMs) may help women receive earlier, more targeted treatment to improve overall health.
Between menarche and menopause, 9-14% of women will experience abnormal uterine bleeding (AUB), which may have significant implications for quality of life and financial health. Prolactin is a hormone produced in the lactotroph cells of the anterior pituitary gland. Hyperprolactinemia can disturb ovarian follicle maturation and corpus luteum function and lead to inhibition of the normal pulsatile secretions of gonadotropin releasing hormone (GnRH) in the hypothalamus. It can also prevent adequate release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) to insufficient levels to induce a proper ovarian response. 
“Hyperprolactinemia can disturb ovarian follicle maturation and corpus luteum function and lead to inhibition of the normal pulsatile secretions of gonadotropin releasing hormone (GnRH) in the hypothalamus.”
Thyroid disorders are prevalent in the female population with ~ 0.8 per 1000 women per year developing spontaneous hyperthyroidism and 3.5 per 1000 per year developing spontaneous hypothyroidism. Thyroid hormones affect the menstrual pattern directly through an effect on ovarian specific thyroid hormone receptors and indirectly via effects on sex hormone binding globulin (SHBG), prolactin, GnRH, and coagulation factors. Several studies have shown 15-26% of menstrual cycle disorders result from thyroid dysfunction. Moragianni and Somkuti  highlighted the importance of thyroid function tests in patients with menorrhagia and concluded that medical treatment provided in an appropriate time frame can resolve the symptoms and preserve fertility potential.
“Thyroid hormones affect the menstrual pattern directly through an effect on ovarian specific thyroid hormone receptors and indirectly via effects on sex hormone binding globulin (SHBG), prolactin, GnRH, and coagulation factors.”
As of the time of publication of the study by Abdel et al,  no consensus existed on screening for hyperprolactinemia and thyroid disorders in patients with menstrual irregularities including oligomenorrhea and amenorrhea. To assess the usefulness of screening, their study measured prolactin and thyroid hormone levels among patients presenting with abnormal menstrual pattern (defined as any change in duration, amount or frequency of menstrual flow excluding oligomenorrhea and amenorrhea) and compared them to the hormone levels in patients with regular menstruation. 
This was a cross-sectional observational study conducted to evaluate the relationship between AUB and abnormal thyroid hormone and prolactin levels. Patients were recruited from outpatient gynecology and infertility clinics in Cairo Egypt and Abu Dhabi, United Arab Emirates. Of the people included in the study, 105 patients met criteria for AUB and 125 patients served as the control population. Eligible women were 20 to 35 years old with a body mass index (BMI) < 30.
Patients in the AUB group had menorrhagia (bleeding for 7+ days with same heaviness throughout), polymenorrhea (frequent cycles of < 21 days), intermenstrual bleeding or mixed patterns. Exclusion criteria included other forms of AUB (oligomenorrhea, primary or secondary amenorrhea), endocrine disorders leading to AUB (adrenal disorder, PCOS), organic causes of AUB (fibroids, polyps or ovarian cysts), hormonal treatment or medications that could affect menstrual flow or prolactin level, suspected malignancy, pregnancy, coagulation disorders, and anticoagulation therapy. The control group consisted of age- and BMI-matched healthy women with regular menstruation.
Patients underwent a thorough clinical evaluation to detect the presence of any organic pathology. The comprehensive exam included inspection for hyperandrogenic manifestations, a breast assessment for galactorrhea, and a vaginal speculum exam. All patients had a vaginal ultrasound. Labs were collected from each patient on days 1-3 of menstruation, including FSH, LH, prolactin, TSH, free T4 and free T3. If uterine lesions were suspected, hysterosonography or diagnostic hysteroscopy was performed. Hyperprolactinemia was defined as a prolactin level > 1.13 nmol/L. Abnormal TSH was defined as a level < 0.5 or > 5.5. Abnormal free T3 and free T4 were defined as levels outside the ranges of 3.6 to 6.5 and 10 to 23, respectively. 
There were no significant differences between groups in age, BMI, parity, or ethnic origin. The most frequent type of AUB was polymenorrhea, affecting 57.1% of patients. Frequency of elevated prolactin was found to be significantly higher in the abnormal uterine bleeding group vs. the control group, and mean prolactin levels differed significantly between the two groups (AUB: 29.5 ± 16.7 [7.4–67.4]; Control: 11.7 ± 6.9 [1.9–31.2]). Elevated TSH alongside low levels of free T3 and free T4 were found to be significantly more common in the AUB group than the control group. However, the frequency of low TSH level alongside elevated free T3 and free T4 levels did not differ significantly between the two groups. A sub-analysis of the AUB group showed galactorrhea was significantly more common among women with hyperprolactinemia. Another sub-analysis of this group showed TSH was elevated in a significantly higher proportion of patients with AUB who had hyperprolactinemia than those who had normal prolactin levels.
In this study, a higher prevalence of hyperprolactinemia was found among patients with AUB accompanied by a higher prevalence of hypothyroidism as indicated by an elevated TSH with decreased free T3 and free T4. It has been suggested that treatment of thyroid dysfunction can reverse menstrual abnormalities and preserve a patient’s fertility potential.  Furthermore, some investigators concluded it is worthwhile to screen for a thyroid disorder in any woman with abnormal menses. 
“In this study, a higher prevalence of hyperprolactinemia was found among patients with AUB accompanied by a higher prevalence of hypothyroidism as indicated by an elevated TSH with decreased free T3 and free T4.”
The study centers went on to implement screening for abnormal prolactin and thyroid hormone levels in all women of reproductive age who have AUB. An elevated prolactin level occurred in only 3.2% of women with normal menses. The study results confirmed a previous finding that galactorrhea was present in 30 to 80% of patients with a high serum prolactin level. 
Strengths of the study by Abdel et al include the use of clearly defined inclusion and exclusion criteria as well as its setting in two different countries with comparable patients, making the results reproducible. The study is limited by the fact that not all possible thyroid function tests were assessed, and different types of prolactin were not measured.
From a medical standpoint, assessing prolactin and thyroid hormone levels in 20 to 35-year-old women who present with abnormal bleeding patterns can be recommended even in the absence of galactorrhea or thyroid manifestations. Such screening could help identify the etiology of AUB and thus the best treatment approach. Additionally, the ability to identify AUB earlier by using fertility awareness-based methods (FABMs) and charting the female cycle may lead to earlier treatment and fewer implications on the quality of life and financial health of women.
 Abdel Hamid AM, Borg TF, Madkour WA. Prevalence of hyperprolactinemia and thyroid disorders among patients with abnormal uterine bleeding. Int J Gynaecol Obstet. 2015 Dec;131(3):273-6. doi: 10.1016/j.ijgo.2015.05.035. Epub 2015 Aug 24. PMID: 26372350.
 Moragianni VA, Somkuti SG. Profound hypothyroidism-induced acute menorrhagia resulting in life-threatening anemia. Obstet Gynecol. 2007 Aug;110(2 Pt 2):515-7. doi: 10.1097/01.AOG.0000275285.04825.07. PMID: 17666648.
 Shin SY, Lee YY, Yang SY, Yoon BK, Bae D, Choi D. Characteristics of menstruation-related problems for adolescents and premarital women in Korea. Eur J Obstet Gynecol Reprod Biol. 2005 Aug 1;121(2):236-42. doi: 10.1016/j.ejogrb.2004.12.017. PMID: 16054969.
 Speroff L, Fritz MA. Clinical Gynecologic Endocrinology and Infertility. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005.
 Poppe K, Velkeniers B, Glinoer D. Thyroid disease and female reproduction. Clin Endocrinol (Oxf) 2007;66(3):309–21.
 Moragianni VA, Somkuti SG. Profound hypothyroidism-induced acute menorrhagia resulting in life-threatening anemia. Obstet Gynecol 2007;110(2 Pt 2):515–7.
ABOUT THE AUTHOR
Liz McAuliff is a fourth-year medical student at the National University of Natural Medicine in Portland, OR. She completed her undergraduate degree at Virginia Tech in Blacksburg, VA, where she achieved dual degrees in human nutrition foods & exercise and Spanish. She enrolled in the FACTS elective to continue to learn about ways to empower and support future patients to engage in their reproductive health and longevity. She acknowledges the importance of identifying and addressing health issues early on. McAuliff plans to pursue residency in family medicine, and her future practice will focus on women’s health and complementary fertility care.