American Diabetes Awareness Month
Endocrine Disorders and Menstrual Disturbances: A Review
By: Erin Kelleher, MD, MS
Editor’s Note: To mark American Diabetes Awareness Month, we are featuring research that compares varying presentations of menstrual disturbances across several common endocrine disorders, including diabetes, polycystic ovary syndrome (PCOS), hyperprolactinemia, and thyroid disorders. Erin Kelleher, a former FACTS elective participant, summarized a 2020 review published in the International Journal of Endocrinology and Metabolism. The summary highlights: the implications of irregular menstrual cycles for endocrine and overall health; the prevalence of oligomenorrhea among women with endocrine disorders; and charting as a cost-effective means of gaining insight into a woman’s menstrual cycle and thus her overall health.
The endocrine system plays a key role in the menstrual cycle. The hypothalamus, pituitary, and ovaries form the HPO axis to regulate a woman’s cycle. The endocrine system interacts and influences the ovarian and endometrial cycles, which ends in either a pregnancy or shedding of the endometrial lining. There is a delicate balance between the HPO axis and the reproductive system — any abnormalities may adversely affect fertility and menstruation.
“There is a delicate balance between the hypothalamic-pituitary-ovarian axis and the reproductive system — any abnormalities may adversely affect fertility and menstruation.”
Menstrual cycle irregularities are one of the most common complaints across all stages of a woman’s reproductive life, although prevalence of menstrual disorders varies from 14.2% to 26% of women depending on the region of the world. Recognizing the importance of the menstrual cycle as a fifth vital sign, researchers Naz et al.  aimed to summarize the menstrual disturbances in different endocrine disorders. The researchers noted that irregular menstrual cycles may be indicative of an underlying chronic condition, such as diabetes or polycystic ovarian syndrome (PCOS).
Researchers conducted a literature search using Google Scholar, PubMed, Web of Science, and Scopus to identify studies, published before December 2019, on menstrual disturbances and endocrine disorders. Reference lists from those studies were also used to find additional studies. This review article summarizes menstrual disturbances in endocrine diseases, such as PCOS, diabetes, hyperprolactinemia, hypothyroidism, thyrotoxicosis, and Cushing’s syndrome  .
Menstrual cycle disturbances in women with PCOS
PCOS has been identified as the most common problem in endocrine practice, and yet, the exact cause of PCOS is still unknown. PCOS causes small cysts to develop, resulting in enlarged ovaries. Symptoms include hirsutism, alopecia, and acne, as well as irregular menstrual cycles. Most women with PCOS present with infrequent menstruation associated with anovulation. In PCOS, prolonged estrogen exposure due to the enlarged ovaries leads to a thickened endometrial lining, which neither responds to the typical inhibitory effect of progesterone nor sheds causing the common experience of amenorrhea. The disturbed HPO axis also causes an increase in LH:FSH, changing the pulsatile secretion of GnRH, which subsequently increases testosterone production.
Obesity is a common clinical manifestation of PCOS and is a risk factor implicated in insulin resistance and symptoms, such as acanthosis nigricans. Current treatment recommendations for PCOS include lifestyle modifications, such as diet and exercise, metformin, anti-androgen medications, and combined oral contraceptive pills, which itself may increase insulin resistance. 
Menstrual cycle disturbances in women with diabetes
Many adolescent and adult women with Type 1 or 2 diabetes mellitus (DM) suffer from menstrual irregularities. DM is a chronic condition that affects 219.3 million women across the globe. Women with Type 1 DM are more likely to suffer from menstrual problems such as heavy menstruation, menstrual irregularities, menstruation lasting longer than six days, and cycle lengths over 31 days. Women with diabetes experience hormonal imbalances similar to those common in PCOS, including increased LH:FSH and androgens, decreased gonadotropin levels, and hyperinsulinemia. These hormonal imbalances share many similarities with PCOS. Minimal research has been conducted on the effect of diabetes management on the menstrual cycle. However, current literature suggests a relationship between LH and serum glucose, with tighter glucose control correlating with better menstrual function.
“Women with Type 1 DM are more likely to suffer from menstrual problems such as heavy menstruation, menstrual irregularities, menstruation lasting longer than six days, and cycle lengths over 31 days.”
Menstrual cycle disturbances in women with hyperprolactinemia
During a healthy woman’s cycle, prolactin levels are low during the follicular phase and rise during the luteal phase. Abnormally elevated prolactin levels, or hyperprolactinemia, can occur due to medications, pathology or normal physiological adaptation (e.g. breastfeeding). Hormones such as thyrotropin releasing hormone and serotonin, opioids, and other neurotransmitters can increase prolactin production. Prolactin suppresses pulsatile GnRH and can also suppress LH secretion, which inhibits ovulation. Women with hyperprolactinemia may therefore experience anovulatory cycles, amenorrhea or abnormal bleeding. Treatment includes dopamine agonist therapy, such as cabergoline or bromocriptine, because dopamine inhibits prolactin secretion.
Menstrual cycle disturbances in women with thyroid disease
The HPO axis and the hypothalamic-pituitary-thyroid axis work together to regulate the menstrual cycle. Dysfunction of the thyroid can change serum sex steroid, sex hormone-binding globulin, GnRH, and prolactin levels and cause menstrual irregularities. Specifically, hypothyroidism may result in oligomenorrhea, while hyperthyroidism may result in polymenorrhagia. Hypothyroidism treatment includes levothyroxine, which mimics T4, and patients have observed improvements in menstrual cycle disturbances. Hyperthyroidism is commonly treated with radioactive iodine.
Menstrual cycle disturbances in women with Cushing’s syndrome
Cushing’s syndrome is an endocrine disorder caused by an excess in glucocorticoid production from the adrenal glands. Symptoms associated include obesity, hirsutism, hypertension, protein wasting, and menstrual irregularities. Menstrual irregularities, such as oligomenorrhea and amenorrhea, are the most common complaint (80%) in women with Cushing’s syndrome. Symptoms of Cushing’s syndrome are closely related to cortisol levels. Management of Cushing’s syndrome includes steroidogenesis inhibitors, glucocorticoid receptor antagonists, ACTH lowering drugs, radiation, and bilateral adrenalectomy. Despite well-documented menstrual disturbances, there remains little research on whether treating Cushing’s syndrome improves menstrual cycle irregularities.
Other endocrine causes of menstrual disturbances
Numerous other endocrine disorders may also affect the menstrual cycle, including primary hyperparathyroidism, non-classical congenital adrenal hyperplasia, acromegaly, and Addison’s disease. This shows the importance of the endocrine system and its role in regulating the menstrual cycle.
This article was the first comprehensive review summarizing the features of menstrual disturbances in several specific endocrine disorders: PCOS, Types 1 and 2 diabetes mellitus, hyperprolactinemia, thyroid disease, Cushing’s syndrome, as well as other less common disorders. This review highlights the delicate balance between the endocrine system, particularly the HPO axis, and the impact on menstrual cycles. Whether a woman presents with an endocrine disorder or a menstrual irregularity, medical professionals should look at the entire hormonal picture instead of focusing on one system. Oligomenorrhea was the most common presentation in women with menstrual cycle disturbances, and the study demonstrates a relationship between irregular cycles and endocrine disorders: a symptom observed in one system may be a useful tool in the diagnosis of the other. Teaching a woman with menstrual cycle abnormalities how to chart her cycle is a cost-effective method to monitor her hormonal health that may facilitate a diagnosis before beginning medications and invasive procedures.
A woman’s menstrual cycle is often a good indicator of her overall health, and cycle irregularities should be investigated and addressed. For example, a woman with PCOS will not only likely experience cycle abnormalities, but she is also at risk for developing insulin resistance, type 2 diabetes and heart disease. Giving a woman oral contraceptive pills and ignoring the risk of insulin resistance may be detrimental to her health in the long term. Therefore, it is important to consider underlying endocrine disorders in women with menstrual irregularities because correcting a disorder, such as hypothyroidism or insulin resistance, may fix these irregularities. Charting the menstrual cycle and timing blood work appropriately to check for hormone imbalances is important before starting treatment. Even a few months of documented cycles can give a clinician a lot of insight into a woman’s cycle and overall health.
“A woman’s menstrual cycle is often a good indicator of her overall health, and cycle irregularities should be investigated and addressed.”
Limitations of this study include its analysis of a combination of endocrine disorders, such as diabetes mellitus and thyroid disease, without concise comparison of the disorders. More research is needed to further understand the complex interactions of the endocrine and reproductive systems and the various disorders and symptoms associated with each. In particular, future studies are needed to determine the interaction of the endocrine system and its role in PCOS.
 Saei Ghare Naz M, Rostami Dovom M, Ramezani Tehrani F. The Menstrual Disturbances in Endocrine Disorders: A Narrative Review. Int J Endocrinol Metab. 2020;18(4):e106694. Published 2020 Oct 14. doi:10.5812/ijem.106694
 Cortés ME, Alfaro AA. The effects of hormonal contraceptives on glycemic regulation. Linacre Q. 2014;81(3):209-218. doi:10.1179/2050854914Y.0000000023
ABOUT THE AUTHOR
Erin Kelleher, MD, MS
Erin Kelleher, MD, MS, is a Pediatrics Intern at the University of Wisconsin-Madison. She completed her medical training at Chicago Medical School at Rosalind Franklin University of Medicine and Science. She plans to specialize in adolescent medicine or hospital medicine. She has a special interest in eating disorders, reproductive health, and high-risk behaviors.