In part 1 of this 3-part series on amenorrhea, I covered the causes of primary amenorrhea, which occurs when a girl never starts having periods. Here, I’ll cover the reasons a girl or woman might experience secondary amenorrhea, meaning that she had periods for a time and then they stopped. Be sure to check out part 3 to learn what to do if you or your daughter experience primary or secondary amenorrhea.
Secondary Amenorrhea
The American College of Obstetricians and Gynecologists (ACOG) defines secondary amenorrhea as the absence of menstruation for three months or more after periods have already begun. The most common reasons that women of reproductive age stop having periods (other than pregnancy and breastfeeding) are hypothalamus malfunction, polycystic ovary syndrome (PCOS), early menopause, pituitary or thyroid gland malfunction, certain medications, illicit drug use, and obesity.
Problems with the hypothalamus
Problems with the hypothalamus can cause secondary amenorrhea. Functional hypothalamic amenorrhea (FHA) occurs when physical or emotional stress causes periods to stop, even with no other underlying health issues [1]. Common contributors to FHA include excessive exercise, undereating, eating disorders, and intense mental or emotional distress.
Stress: the great enemy of healthy ovulation
Stress alone can wreak havoc on our cycles, and in various ways—it can delay ovulation and cause longer periods, it can shorten the luteal phase and make menstruation happen sooner, or it could suppress ovulation entirely, leading to secondary amenorrhea. Unfortunately, health conditions and circumstances that prevent healthy ovulatory cycles often bring a load of stress with them, resulting in a vicious cycle: stress contributes to a hormonal imbalance, which a woman may only realize she has because the imbalance causes other health problems, and the symptoms of those issues then exacerbate her feelings of stress. It’s no wonder that functional hypothalamic amenorrhea is linked to depression and anxiety [2]!
When stress arises from another medical condition, it’s possible that treating the underlying disease can relieve the symptoms and stress, to restore missing periods. To be sure, nonmedical issues can also generate a great deal of stress, but in one small study, cognitive behavioral therapy (CBT) alone was successful in restoring periods for women with hypothalamic amenorrhea [3]. More research in this area is undoubtedly needed, but the interconnectivity of the reproductive system’s cyclical hormonal activity and the daily functioning of our bodies and brains suggest that caring for ourselves mentally and emotionally can have a powerful impact on our physiological health as well.
Exercise-induced amenorrhea
It is a well-known occurrence for women who are athletes or who regularly perform intense physical activity to lose their periods. While it may be common, it should not be considered normal. Some athletes, acting under the belief that they can only perform better and faster by being as lean and light as possible, restrict their food intake by calories, food groups, or types of macronutrients. In other cases, many female athletes simply aren’t eating enough to replenish the energy they’re expending through rigorous training and competition.
Whether it’s a conscious choice to under-eat or not, when the body experiences a regular calorie deficit, it tries to conserve energy every way it can. One can easily imagine: a malnourished athlete feels fatigued and achy as her body tries to signal her to conserve more energy, but pushes through, training just as hard or even harder to achieve her goals. Her body, going into survival mode, will stop ovulating to conserve energy, maintain basic functions, and prevent pregnancy, which would require even more of the nutrients she’s already lacking.
Low body weight or undereating
Even without intense physical activity, undereating can trigger the reproductive system to pause ovulation. Low body weight is often linked to functional hypothalamic amenorrhea which is accompanied by low estrogen and a low ratio of luteinizing hormone (LH) to follicle stimulating hormone (FSH) [4]. Because some of the symptoms of hypothalamic amenorrhea are similar to that of PCOS (including ovarian cysts), women who experience it may be misdiagnosed with PCOS, even though the treatments are reverse: restoring ovulation and periods by eating more as opposed to managing the symptoms of PCOS by eating less.
Eating disorders
Losing a period is one of the most common side effects of eating disorders, regardless of what type of eating disorder one has or of one’s prior weight [5][6]. Anorexia and bulimia often involve several factors in combination—rapid weight loss, a sustained period of low body weight, and psychological distress—that cause the body to stop menstruating [7]. Women with binge eating disorder, while they may not be underweight, are still more likely to stop having periods than women without eating disorders [8]. Furthermore, research suggests that women with PCOS may be more prone to binge eating [9]. Tellingly, doctors who treat female patients with eating disorders look for menstruation as a marker of recovery, a signal that the body is returning to a more stable state of health and is no longer in survival mode.
Mental health issues
As previously discussed, what happens in our brains has a lot to do with our fertility, and vice versa. You’re not crazy for feeling different depending on where you are in your cycle—as estrogen and progesterone levels rise and fall, they stimulate neurological growth and repair in the brain, prompting changes in mood (although regularly experiencing extreme mood swings, sadness, or anxiety could be signs of premenstrual dysphoric disorder (PMDD), a prevalent neuroendocrine disease).
This also means that when things are off with our mental health, the reproductive cycle suffers too. Secondary amenorrhea is a common side effect of depression, which leads to increased levels of the stress hormone cortisol. This can stop the hypothalamus from producing gonadotropin-releasing hormone (GnRH), thereby preventing ovulation. Depression can also indirectly cause periods to stop because of other factors like increased or decreased appetite leading to either weight gain or loss.
Many other mental health issues cause hormone levels to become imbalanced and therefore can be an underlying cause of amenorrhea, including anxiety, bipolar disorder, and obsessive-compulsive disorder (OCD). Unfortunately, in some cases, pharmacological treatment for mental health disorders can have an adverse effect on menstrual cycles.
Medications and secondary amenorrhea
Many medications, both prescription and over-the-counter, interfere with the ovulatory cycle and fertility because they raise the levels of prolactin in the body. This is true of antipsychotic medications like risperidone (Risperdal) and quetiapine (Seroquel) used to treat mood and anxiety, bipolar, and obsessive-compulsive disorders. Antidepressants have also been shown to negatively impact hormonal regulation and pregnancy outcomes [10].
Do you know what doctor-prescribed treatment negatively impacts both fertility and mental health? Hormonal birth control (HBC). A study of over 1 million women showed that using either a combination or progestin-only Pill, patch, ring, or IUD increases the likelihood of being subsequently diagnosed with depression [11]. Many women are prescribed the Pill by their doctors to “treat” irregular periods, hormonal imbalances, or the symptoms of reproductive health issues like PCOS, even though HBC simply masks symptoms rather than addressing the underlying condition.
While HBC mimics a period by producing a monthly withdrawal bleed, the reality is that while taking birth control, ovulation is suppressed and menstruation does not occur. Rather than actually balancing hormone levels, birth control introduces artificially high levels of synthetic progesterone to trick the body into thinking it has already ovulated. When a woman stops taking the pill, whatever was causing her hormones to fluctuate improperly before is likely to return. And for many women, it can take months for periods to return after quitting hormonal birth control.
Illicit drug use
In some cases, women may self-medicate for cramps and other period symptoms with drugs and alcohol; it was also found in a study that women’s drug usage followed a pattern based on where they were in their menstrual cycles [12][13]! Along with a host of other issues, use of illicit drugs, including methamphetamine, cocaine, heroin, and methadone is also associated with secondary amenorrhea.
PCOS and secondary amenorrhea
Polycystic ovary syndrome (PCOS), the most common cause of infertility in women, occurs because of an excess of testosterone (which all women naturally have small amounts of). PCOS is characterized by a number of symptoms including heavy bleeding, acne, fatigue, Type 2 diabetes, and ovarian cysts. Because of the hormonal imbalance at the root of PCOS, irregular menstrual cycles and missing periods nearly always accompany the condition.
Early menopause and secondary amenorrhea
Premature ovarian failure, or primary ovarian insufficiency, is when menopause begins before the age of 40 [14]. Although it is usually accompanied by estrogen deficiency, no singular cause of premature menopause has been determined. It is known to occur more commonly among women who previously experienced primary or secondary amenorrhea. The many potential causes of early menopause include genetic disorders such as Fragile X syndrome, autoimmune disorders, metabolic disorders such as enzyme deficiencies, viral infections such as mumps; chemotherapy or radiation therapy for cancer; surgical removal of the ovaries or uterus; or exposure to toxins like drugs or tobacco.
Thyroid malfunction
How can thyroid issues cause secondary amenorrhea? Together, the thyroid and pituitary glands regulate the body’s hormone levels, so thyroid health is crucial for ovulation and menstruation. While more research is needed to understand how thyroid issues impact ovulation, menstruation, and fertility, studies have shown that menstrual irregularities are far more common for women with hyperthyroidism than those without thyroid issues [15]. Symptoms like mid-cycle spotting and short cycles are most likely to show up as a result of an overactive thyroid, but lack of menstruation altogether is also possible. An underactive thyroid gland (hypothyroidism) results in lower-than-normal levels of thyroid hormones in the body, which can cause menstrual irregularities, including amenorrhea. Check out the three-part series previously published by Natural Womanhood that dives deep into the physiology of hypothyroidism and explains why the usual treatments fall short in addressing both the underlying causes and symptoms.
Pituitary tumor or brain injury
Another, less common underlying cause of secondary amenorrhea is a pituitary tumor. Located in the brain and about the size of a pea, the pituitary gland acts as the command center for hormone regulation, signaling to the ovaries, thyroid, and adrenal glands which and how much hormones to produce. Tumors on (or near) the pituitary gland are rare and most are noncancerous; when present, they disrupt hormonal regulation around the entire body, including ovulation and menstruation.
As mentioned previously in part 1 of this series, brain damage can also be a cause of missing periods; even a mild concussion can lead to a drop in circulating hormone levels, and a severe head injury can cause periods to stop entirely.
Obesity
Finally, being overweight can lead to amenorrhea because adipose tissue (fat cells) produce estrogen. It may seem backwards that high amounts of estrogen, the dominant hormone in ovulation, would cause periods to stop, but when it comes to healthy ovulation, having the right balance between hormone levels is key. Too much or too little of anything can send the cycle awry.
The bottom line about secondary amenorrhea
You might have read all of the above and thought “yikes! I could have one or more of these causes! How can I know what’s causing my amenorrhea?” We’ve got you covered. In part 3 of this series on amenorrhea, we cover what to do when you are experiencing amenorrhea, whether primary or secondary. We specifically emphasize the importance of working with a healthcare provider (or whole team!) trained in restorative reproductive medicine (RRM).
References:
[1] Podfigurna A, Meczekalski B. Functional Hypothalamic Amenorrhea: A Stress-Based Disease. Endocrines. 2021; 2(3):203-211. https://doi.org/10.3390/endocrines2030020 [2] Meczekalski, B., Katulski, K., Czyzyk, A. et al. Functional hypothalamic amenorrhea and its influence on women’s health. J Endocrinol Invest 37, 1049–1056 (2014). https://doi.org/10.1007/s40618-014-0169-3 [3] Berga, Sarah L et al. “Recovery of ovarian activity in women with functional hypothalamic amenorrhea who were treated with cognitive behavior therapy.” Fertility and sterility vol. 80,4 (2003): 976-81. doi:10.1016/s0015-0282(03)01124-5 [4] Abou Sherif, Sara et al. “Investigating the potential of clinical and biochemical markers to differentiate between functional hypothalamic amenorrhoea and polycystic ovarian syndrome: A retrospective observational study.” Clinical endocrinology vol. 95,4 (2021): 618-627. doi:10.1111/cen.14571 [5] Poyastro Pinheiro, Andréa et al. “Patterns of menstrual disturbance in eating disorders.” The International journal of eating disorders vol. 40,5 (2007): 424-34. doi:10.1002/eat.20388 [6] Rastogi, Radhika & Sieke, Erin & Nahra, Alexa & Sabik, Julia & Rome, Ellen. (2019). Return of Menses in Previously Overweight Patients with Eating Disorders. Journal of Pediatric and Adolescent Gynecology. 33. 10.1016/j.jpag.2019.11.002. [7] Gendall, Kelly A et al. “The psychobiology and diagnostic significance of amenorrhea in patients with anorexia nervosa.” Fertility and sterility vol. 85,5 (2006): 1531-5. doi:10.1016/j.fertnstert.2005.10.048 [8] Algars M, Huang L, Von Holle AF, Peat CM, Thornton LM, Lichtenstein P, Bulik CM. Binge eating and menstrual dysfunction. J Psychosom Res. 2014 Jan;76(1):19-22. doi: 10.1016/j.jpsychores.2013.11.011. Epub 2013 Nov 28. PMID: 24360136; PMCID: PMC3909535. [9] Krug I, Giles S, Paganini C. Binge eating in patients with polycystic ovary syndrome: prevalence, causes, and management strategies. Neuropsychiatr Dis Treat. 2019 May 16;15:1273-1285. doi: 10.2147/NDT.S168944. PMID: 31190833; PMCID: PMC6529622. [10] Domar, A D et al. “The risks of selective serotonin reuptake inhibitor use in infertile women: a review of the impact on fertility, pregnancy, neonatal health and beyond.” Human reproduction (Oxford, England) vol. 28,1 (2013): 160-71. doi:10.1093/humrep/des383 [11] Skovlund CW, Mørch LS, Kessing LV, Lidegaard Ø. Association of Hormonal Contraception With Depression. JAMA Psychiatry. 2016;73(11):1154–1162. doi:10.1001/jamapsychiatry.2016.238 [12] Substance Abuse Treatment: Addressing the Specific Needs of Women [Internet]. Rockville (MD): Substance Abuse and Mental Health Services Administration (US); 2009. (Treatment Improvement Protocol (TIP) Series, No. 51.) 3 Physiological Effects of Alcohol, Drugs, and Tobacco on Women. Available from: https://www.ncbi.nlm.nih.gov/books/NBK83244/ [13] Stevens, Sally J et al. “Women and substance abuse: gender, age, and cultural considerations.” Journal of ethnicity in substance abuse vol. 8,3 (2009): 341-58. doi:10.1080/15332640903110542 [14] Okeke T, Anyaehie U, Ezenyeaku C. Premature menopause. Ann Med Health Sci Res. 2013 Jan;3(1):90-5. doi: 10.4103/2141-9248.109458. PMID: 23634337; PMCID: PMC3634232.[14] Poppe, Kris et al. “Thyroid disease and female reproduction.” Clinical endocrinology vol. 66,3 (2007): 309-21. doi:10.1111/j.1365-2265.2007.02752.x [15] Poppe, Kris et al. “Thyroid disease and female reproduction.” Clinical endocrinology vol. 66,3 (2007): 309-21. doi:10.1111/j.1365-2265.2007.02752.x.
