Due to the hectic lifestyles that Singaporeans lead, many don’t settle down until they’re in their 30's. Most couples are usually in their early to mid 30's when they start family planning.
Many women are also on the contraceptive pill throughout most of their 20s, which may mask any underlying hormonal issues. This gives them a false sense of security.
I commonly see patients in my endocrine clinic who had no idea that they were having hormonal issues in the first place (until they started trying for a baby)!
In this article, I describe 5 conditions where hormones can affect fertility, as well as the corresponding treatments.
When should you get checked for infertility?
Most of us are well aware that infertility increases with age, especially for women. The effect of a woman’s age is more significant than that of a man’s, but advanced male age is a factor too.
If a woman is under the age of 35 and has difficulty conceiving for one year despite regular intercourse, this warrants further evaluation.
The same goes for older women who have been trying for 6 months or more.
What causes infertility?
The underlying cause for the infertility can be female or male causes, both, or neither (unexplained).
Most endocrine (hormonal) causes of infertility in women affect ovulation. Having regular menstrual cycles indicate that a woman is ovulating about 95% of the time.
There is a small proportion of women who have regular cycles but don’t ovulate.
If your cycles are irregular, then you are most likely not ovulating.
Apart from premature menopause, the other endocrine causes of infertility are treatable. However, the effectiveness of treatment may vary.
How do hormones affect fertility?
To understand how hormones can affect fertility, one must first understand how hormones are produced.
The Hypothalamic-pituitary gonadal axis
The pituitary gland is a pea-sized gland situated at the base of the brain (coloured purple in the gif above). It's responsible for producing all the hormones in your body.
It receives information from a higher centre called the hypothalamus (in the brain) and sends signals to various organs in your body.
The axis responsible for the female and male hormones is called the hypothalamic-pituitary gonadal axis (ovaries in females and testes in males).
In a nutshell, this is how it works:
- The hypothalamus secretes gonadotropin releasing hormone (GnRH)
- GnRH signals the pituitary gland to produce luteinizing hormone (LH) and follicle stimulating hormone (FSH).
LH is responsible for oestrogen production (in women) and testosterone production (in men).
FSH is responsible for follicle development (in women) and sperm production (in men).
Any problems along any part of this axis will affect the production of female and male hormones.
What hormonal conditions are associated with infertility?
1. Hypogonadism (low oestrogen levels)
One of the most common causes of low oestrogen levels that I see in my clinic is hypothalamic amenorrhoea - a problem in the hypothalamus that affects periods.
In this situation, the hypothalamus stops sending signals to the pituitary gland and results in low oestrogen production. I.e., low GnRH leads to low FSH and LH and consequently low oestrogen.
As a result, if you have hypogonadism, your periods usually become lighter or stop completely.
Low oestrogen levels can cause:
- Low mood
- Vginal dryness with pain during intercourse
- Reduction in energy levels
If you are affected, you may not feel up to sexual intercourse. An important cause of hypothalamic amenorrhoea is a having a low body weight, either as a result of excessive dieting, exercise or both.
Management involves weight regain and maintenance of a normal body weight. This may not be acceptable to you if you wish to retain your thin body habitus.
Sometimes, if your weight loss has been present for a long time, it may take a while for your periods to return. Although fertility can be restored by treatment of FSH/LH or GnRH, it is important that you regain a healthy weight before trying to conceive.
Otherwise, the lack of adequate nutrition will affect your baby’s growth and development.
1.1 Low oestrogen levels due to premature menopause
A much less common but still important cause of low oestrogen is premature menopause. The normal age for menopause to start is about 50 years old, and is considered premature if occurs before the age of 40.
If your periods stop and you experience symptoms of menopause (eg hot flushes), you will notice pretty quickly and can seek treatment for these symptoms.
However, if you are on the oral contraceptive pill, you will only realize something is wrong when you come off the pill and notice that your periods haven’t returned.
Premature menopause may be due to:
- Autoimmune condition (up to 1/3 of these women may have another autoimmune condition, most commonly hypothyroidism)
- Chromosomal abnormalities
- Previous chemo/radiotherapy
- Unidentifiable causes
A large proportion of women with premature menopause have no identifiable cause. As they have almost no eggs left, their chance of spontaneous conception is less than 5%.
If you experience premature menopause, your chance of spontaneous conception is not completely zero. There have been women who have experienced a spontaneous return of ovarian function.
I have a young woman under my care who has premature menopause and conceived spontaneously and delivered a healthy baby. But this is more the exception than the rule.
However, there is nothing that can help predict if this will occur and no treatment that will increase the likelihood of this happening.
I usually start my patients on hormone replacement therapy as this will help with their symptoms of menopause. As this is not a form of contraception, the rare occurrence of conception can still occur.
Indeed, if you are sexually active and do not want to have children, I would advise you to continue to use some form of contraception.
2. Hyperprolactinemia (high prolactin levels)
Prolactin is a hormone produced by the pituitary gland. An excess of prolactin causes galactorrhoea (breast milk production). It also affects ovulation and causes infertility. It can affect the gonadal axis at any level (hypothalamus, pituitary or ovary).
If you have hyperprolactinemia, you will experience irregular or absent periods. However, there are some women who have monthly periods and only realize they have high prolactin levels when they are get blood tests done to evaluate infertility.
This can be effectively treated with medications, and fertility is usually restored once prolactin levels normalize.
3. Polycystic Ovary Syndrome (PCOS)
PCOS causes infertility by preventing ovulation from taking place.
Weight loss and improvement in insulin sensitivity may restore ovulatory cycles. If this fails, there are medications such as Clomiphene that help induce ovulation.
The pregnancy rate in women with PCOS (including PCOS women who have received treatment such as ovulation induction) is excellent and is similar to that of the general population. You may require some help along the way but the outcomes are generally positive.
Want to know more about PCOS? Why not check out: Essential Guide to PCOS in Singapore?
4. Congenital adrenal hyperplasia (CAH)
This is a rare condition where one of the enzymes responsible for steroid production is deficient. This means that the body is unable to make enough steroid hormones (in this case, the hormone cortisol).
In response to this, the body pushes the adrenal gland harder to correct the low cortisol. A downstream effect of this is increased testosterone production.
If you have CAH, you would be given daily steroid medications and put under the care of endocrinologists. Once steroid doses are optimal, you will find you have regular periods and would be able to conceive naturally.
Non-classic CAH is the mildest form of CAH and usually presents with unwanted hair growth or irregular periods. If steroid treatment doesn’t work, Clomiphene can be tried, as women with CAH have a higher incidence of PCOS.
5. Thyroid dysfunction
Hyperthyroidism (overactive thyroid gland) causes symptoms such as:
- Palpitations (feeling your heart beat really quickly)
- Heat intolerance
- Weight loss
- Menstrual irregularities
Conversely, hypothyroidism (underactive thyroid gland) causes symptoms such as:
- Cold intolerance
- Weight gain
- Menstrual irregularities.
Hyperthyroidism is effectively treated with antithyroid medications such as Carbimazole or Propylthiouracil (radioactive iodine treatment is contraindicated if you are trying to get pregnant). Once thyroid function normalizes, regular menstrual periods should be restored.
Hypothyroidism is effectively treated with thyroxine.
If you find that your periods are still irregular despite restoring normal thyroid function, other causes need to be considered. One of my patients with hypothyroidism had persistently absent periods even after her thyroid function had normalized, and further evaluation revealed the presence of premature menopause.
What about hormonal causes for infertility in men?
Endocrine causes account for under 5% of male infertility. A semen analysis should be done in the first instance.
There are different aspects of the sperm that is evaluated. An abnormal result can be due to:
- Low sperm concentration
- Abnormal morphology (how the sperm look)
- And/or abnormal motility (how fast the sperm swim)
As with women, any condition that affects the hypothalamic-pituitary-gonadal axis can affect testosterone levels and fertility.
Low testosterone resulting from problems with the hypothalamus and pituitary is treatable with LH/FSH.
LH is usually given first and once testosterone level normalizes, semen analysis is repeated. There have been situations where replacing LH alone results in improvement in semen analysis.
If the problem is at the level of the testes, as with premature menopause in women, there is not much that can be offered medically and testicular sperm extraction can be considered (with varying degrees of success).
What can you expect during your initial consultation?
A thorough history from both partners is crucial. This allows for exclusions to be made from the possible list of conditions described above.
There are some important points you should tell your doctor:
- Duration of infertility
- Fertility in previous relationships/previous pregnancies
- Previous medical/surgical histories
- Sexual dysfunction
- Frequency and timing of intercourse
The examination should assess for potential causes of infertility.
- Body habitus (too thin or overweight)
- Signs of excess male hormones in women
- Signs of hyper/hypothyroidism
This is followed by blood tests which test for (but are not limited to):
- LH levels
- FSH levels
- Prolactin levels
- Thyroid function
- Oestrogen/testosterone levels
If any abnormality is found, treatment can be initiated.
Apart from premature menopause in women and testicular failure in men, treatment can be offered for all other endocrine causes of infertility. Hence, it is well worth your time to get an evaluation done.
Dr Marilyn Lee served as Adjunct Assistant Professor in Medicine at Yong Loo Lin School of Medicine (NUS), and is currently a committee member of the Chapter of Endocrinologists (Academy of Medicine Singapore). Dr Lee previously set up the reproductive endocrine service at Khoo Teck Puat Hospital. She deals with all aspects of endocrinology, and has a special interest in reproductive endocrinology. Dr Lee has 2 young daughters, and they enjoy traveling and exploring new places.