by Dr. Sarah King ND
Upper Beach Health & Wellness
1937 Gerrard St E
Toronto, ON, M4L2C2
Your period is late—really late. You’re not pregnant, and you’re not menopausal. You may have missed one cycle or several. Of course, it’s worrisome: Many women who have missed one or more periods often take several pregnancy tests just to be certain. But the causes of a missed period go well beyond the possibility of pregnancy.
“Secondary amenorrhea” is a term used to describe absent menstruation, unrelated to pregnancy, breast-feeding, or menopause, in a woman who previously had regular menstrual periods. Several disorders affecting hormonal regulation can cause secondary amenorrhea; however, 30–35% of cases are due to a condition called hypothalamic amenorrhea (HA).
HA occurs in the absence of structural abnormalities or other organic diseases, and with a higher incidence in athletic women. Acute or chronic energy deficits (via weight loss or body-fat loss), or other physical or psychoemotional stress can disturb the neuroendocrine system, causing a hormonal imbalance.
Each of these conditions—weight loss, overexercising, and perceived stress—all negatively affect the regulation of the hypothalamic-pituitary-ovarian (HPO) axis, resulting in cessation of ovulation (anovulation).
Missing a few periods may not seem like a big deal. In fact, some women may welcome a break from their flow, but the long-term consequences of hormone dysfunction can be severe. If left untreated, these disruptions can lead to impaired lipid and glucose metabolism, abnormal cortisol levels, and increased anxiety and depression. Estrogen on its own is crucial for bone accretion (until the age of about 24–30) and bone maintenance, as well as for cardiovascular protection. Therefore, on the long term, there is an increased risk of osteopenia and osteoporosis, and for those women younger than 30, a challenge in trying to achieve a healthy peak bone mass.
The HPO Axis and Causes of Dysfunction
The HPO axis is a regulated hormonal relationship between the hypothalamus and pituitary gland in the brain and the ovaries, acting as a chain of signals. Genazzani et al have called the hypothalamus the “hormone control centre.” This particular area of the brain is sensitive to adrenal hormone levels, and to other hormones by means of feedback loops.
These signals can impair secretion of gonadotropin-releasing hormone (GnRH), a messenger hormone that affects the ovaries and estradiol secretion. Low estrogen levels, especially in the follicular phase of the menstrual cycle, can prevent ovulation or lead to sporadic ovulation and irregular cycles.
Disordered eating and female triad syndrome have both been associated with low levels of luteinizing hormone (LH). LH, secreted by the pituitary gland, pulses with the menstrual cycle and triggers ovulation. The combination of both low estrogen and low or abnormal pulses of LH increase the likelihood of an anovulatory menstrual cycle and a thin uterine lining.
Mental and Emotional Stress
Stress in general acts as a signal (or multiple signals) to our body and brain. Stress can be described in many ways. Physiologically, it’s an adaptive response to external or internal stimuli that activate different pathways in the body. How stress is experienced and interpreted will differ from person to person, though. Psychosocial or perceived stressors are often challenges in our lives that push us further than we’re able to cope. They can be mentally and emotionally draining, and may or may not be in one’s control.
Stressful situations that affect hormonal systems may include going away to school, starting a new job, uprooting your family to a new living situation, a death in the family, an end to a relationship, and so much more, all of which can cause amenorrhea.
When something is interpreted as stressful, a cascade of pathways are activated in the body to increase survival. The body is programmed to reallocate resources in times of need. When a person begins to feel overwhelmed, stretched too thin, dealing with internal turmoil, the body responds to this stress as if survival depends on it. Some reactions include increased glucose in the blood, increased heart rate, inhibition of digestion, and decreased thyroid hormones to help prevent energy depletion.
Meanwhile, cortisol levels increase, affecting multiple systems including interruption of thyroid function. One study showed that women with HA had elevated serum cortisol, whereas those with amenorrhea from other causes (e.g. polycystic ovarian syndrome) did not have the same elevations. Additionally, once women with HA recovered ovarian function, their serum cortisol levels decreased compared to those who had not regained ovulation.
These changes and the perception of stress leads to increased levels of beta-endorphin in the hypothalamus. This impairs GnRH, therefore disrupting the HPO axis, resulting in low-functioning ovaries. Without enough estrogen and LH, ovarian follicles are no longer encouraged to develop, meaning no mature egg, and certainly not one to send out toward the uterus. The uterus itself, without enough estrogen, will be unable to obtain proper thickness, and therefore has nothing to shed (no “bleeding” of menstruation).
One study that tracked women’s daily perceived stress and their sex-hormone levels reported that women with high perceived daily stress had lower estrogen and LH levels as well as lower luteal progesterone and an increased chance of anovulation.
Sport, Exercise, and Weight Loss
HA is more commonly found in athletic women, but more so in those who maintain a lower body weight and undergo intensive training. This doesn’t mean it only affects Olympic athletes; long-distance runners, gymnasts, dancers, and swimmers all are at risk, and the prevalence of HA is up to 69% of all female athletes in these categories.
One study reported a positive association between the incidence of amenorrhea in runners and the number of miles run per week, independent of body-fat percentage, which can also be a factor leading to amenorrhea.
Low bone density is a known sequelae of chronically low estrogen levels. It is incurred by a caloric imbalance: Insufficient caloric intake from the diet with an excess of calories burned during exercise/training. The resulting low estrogen and disrupted hormonal systems lead to amenorrhea and low bone density. The combination of low energy availability with amenorrhea and low bone density is known as “female athlete triad” or “female triad syndrome.”
Similar outcomes occur in women with disordered eating, as the body attempts to function with insufficient calories and energy, reallocating resources to only the most vital processes. Rapid weight loss or the maintenance of a low body weight, even from one-time “diet programs,” can also cause HA. When a woman’s body-fat percentage falls below about 18% (or if body mass index [BMI] falls below 19), the same pathways are triggered to halt ovulation and menses.
Treatment: Getting Your Period Back
To restore ovulation and menstruation, the primary cause of the dysfunction must be eliminated. First, the physical obstacles must be addressed. This includes increasing caloric intake and decreasing physical activity, which may necessitate counselling for healthy lifestyle habits.
It’s important to work with a licensed practitioner to develop a safe plan for optimizing the BMI and body-fat percentage. Major changes in diet and lifestyle can have positive effects in the long run, but on the short term need to be managed appropriately. In other cases, women may need extra support to help modify their attitudes towards food and exercise and to change their habits in these areas.
Cognitive behavioural therapy (CBT) is an evidence-based treatment aimed to modify attitudes and habits by reflecting on an individual’s automatic thoughts, feelings, and actions.
One study gave women with HA one of two sets of treatments: 16 sessions of CBT over 20 weeks, or observation only for 20 weeks. The first six sessions focused on evaluating nutrition and exercise habits and the attitudes towards each, whereas the remaining sessions focused on stress management techniques and tools for adopting healthier attitudes. Of the women who received CBT, 75% resumed ovulating. Meanwhile, of those who received observation only, 33% were able to obtain partial ovarian recovery, but 67% remained amenorrhoeic and anovulatory. Researchers also noted a significant decrease in nighttime cortisol levels following CBT compared to baseline and to those women who had observation only.
Managing and lowering psychoemotional stress is essential in recovering from HA. There are many therapeutic options available depending on the source of stress and the circumstances in which an individual woman finds herself. In some cases, simply working on stress management via counselling, journaling, yoga, and meditation may help. For others, intensive therapy or botanical preparations may be necessary.
One area of botanical medicine focuses on plants with “adaptogenic” properties. These plants, known as adaptogens, are used to enhance resistance to stress. Botanicals such as Chinese ginseng (Panax ginseng) and rhodiola (Rhodiola rosea) have been used to increase energy and improve mental and physical stamina. Others, like ashwagandha (Withania somnifera) can assist in the conversion of thyroid hormones. Each herb has its own mechanisms based on numerous constituents. For example, ginsengs primarily act on the hypothalamic-pituitary-adrenal (HPA) axis, while rhodiola seems to act on neurotransmitter systems and endorphins. Both can help reduce anxiety and help improve mental performance. More studies are needed to test individual preparations in women with HA.
Acetyl L-carnitine has demonstrated effectiveness in modulating hypothalamic secretion of GnRH. Two studies have now shown that in women with HA and low LH levels, treatment with acetyl L-carnitine significantly increased LH plasma levels and the LH pulse amplitude. The first used a dose of 1 g per day for 16 weeks, while the second used a combination of 500 mg L-carnitine and 250 mg acetyl L-carnitine for 12 weeks, and also found a decrease in plasma cortisol levels in women with baseline low LH.
If a woman is physically or mentally stressed, including from insufficient caloric intake, overexercising, and is faced with challenging and overwhelming life situations, her body will try to conserve energy and reallocate its focus to surviving this stress. Ovulation temporarily shuts down due to inadequate hormone levels; however, these pathways can be restored. In summary, treatment options for HA include:
- Optimizing BMI and body-fat percentage with changes in dietary and athletic habits;
- Seek counselling or therapy such as CBT;
- Use of adaptogenic herbs and acetyl L carnitine;
- Other stress management tools such as journaling, yoga, and tai chi.