Illustration by Marta Pucci
Sex Hormone Binding Globulin (SHBG) 101
Getting to know our hormones.
Hormones are so much more interesting than what we’re taught in health class. So we’ve created a guide to aaaall of the hormones. Here's everything you need to know about estrogen, progesterone, androgens, progestins, synthetic estrogen, and sex hormone binding globulin (SHBG).
Top things to know:
SHBG helps to control the the amount of sex hormones available to the body—this helps keep sex hormone-related processes in balance
SHBG may be related to insulin function, affecting conditions like metabolic syndrome and PCOS
SHBG is important even after menopause—those with high levels of SHBG have a lower risk for developing postmenopausal breast cancer
What is Sex Hormone Binding Globulin?
Sex hormone binding globulin (SHBG) is a protein that affects the function of some sex hormones, including testosterone and estrogen (1,2). It is primarily made in the liver (1).
In short, SHBG binds to specific sex hormones, removing them from direct circulation in the body (1).
What does SHBG do for the body?
In the bloodstream, sex hormones can be found in two forms: free and bonded. Hormones can bind to different molecules. In the case of testosterone and estrogen, one of those molecules is SHBG. Another is the protein albumin (1,2).
When a sex hormone is either free or bonded to albumin, the hormone is considered to be bioavailable (1). This means it can enter tissue and have a biological effect.
In contrast, when bound to SHBG, the sex hormone is essentially inactive and has minimal—if any— biological impact on the body until it’s released (1).
In this way, SHBG acts almost as buffer, controlling the amount of sex hormones available to the body. This helps keep sex hormone-related processes in balance.
In women and people with female reproductive organs, the vast majority of testosterone and estradiol in the blood are bound to SHBG and other proteins, and are not bioavailable—only around 2% of these sex hormones are free to bind to receptors and make an impact on the body (3,4).
SHBG can also release hormones at specific tissues and possibly into cells directly (1,2). This binding has an effect on both the sex hormones and on SHBG. Sex hormones that are bound to SHBG don’t impact the function of the body until they are released, and sex hormones bound to SHBG can affect how well SHBG binds to its own receptor (1).
(Receptors are like locks, and only certain keys—like hormones, or SHBG—can open the locks.)
Low SHBG levels: how do they impact the body? Effects & associations
Because SHBG binds to sex hormones, its relative level can affect levels of sex hormones available to be used by the body—thus having an impact on the processes that sex hormones regulate.
For example, when SHBG levels are relatively low in women, testosterone levels can become abnormally high, causing side effects like hirsutism and acne (2).
There also may be a relationship between SHBG, testosterone, and libido (sex drive). (We delve into that in this article.)
SHBG may have a relationship to other bodily processes, too.
Low SHBG levels are also associated with:
metabolic syndrome
insulin resistance
type 2 diabetes
cardiovascular risk
gestational diabetes
It's not clear if SHBG levels impact these disorders, or vice versa (1,5-7).
SHBG and PCOS
Relatedly, people with polycystic ovary syndrome (PCOS), a disorder associated with metabolic syndrome, tend to have low levels of SHBG (2,5,8). This might be driven by high levels of androgens (a class of hormones that includes testosterone) which both causes sex hormone imbalances and suppresses SHBG production in people with PCOS (5).
SHBG and weight
SHBG levels are also associated with weight. In general, SHBG decreases as weight increases (5,9,10). People with anorexia nervosa have high levels of SHBG, while people who are obese tend to have low levels (5,9,10).
How do I know if my SHBG levels are normal?
Everyone has their own unique “normal” when it comes to hormones, and what is “normal” changes over the course of a person’s life.
That being said, on average, SHBG levels fluctuate as we age. Levels start out high throughout childhood then fall at the onset of puberty, between ages 9 and 12 for most people (9). As someone progresses through puberty, their level of SHBG rises again (11).
For non-pregnant cis-women and people with female reproductive organs, “normal” SHBG levels usually fall between 18 and 144 nmol/L after puberty (9).
Studies have found that ethnicity may also impact SHBG levels. In one small study, SHBG levels were found to be lower in non-Swedish women than Swedish women, but the levels for both groups of women were still in the normal range (18 and 144 nmol/L) (12).
Does the menstrual cycle affect SHBG levels?
Studies have found that SHBG levels may fluctuate over the course of the menstrual cycle. In one study on women with cycles lengths of 25 to 31 days, the average SHBG level peaked around ovulation and was lower during the early follicular phase and the luteal phase (13).
(This might occur because estrogen levels affect SHBG (9,14). Estrogen peaks just prior to ovulation, and so it’s possible the increase in SHBG around ovulation is due to fluctuating estrogen levels. But this is only a guess.)
However, ranges of SHBG levels were the same across all phases of the cycle for 95% of participants (13), which suggests that not everyone necessarily experiences fluctuation.
More research is needed to confirm these results and to understand why this fluctuation happens (if it happens at all).
Cycle length may be associated with SHBG levels. In one study, SHBG levels were higher in people with cycles less than 26 days than people with cycles 27+ days (15).
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How does hormonal birth control affect levels of SHBG?
Hormonal birth control (like the pill, the implant, and hormonal intrauterine devices) affects levels of SHBG, depending on the birth control type.
The impact of hormonal contraceptives on SHBG levels—and the resulting effect of SHBG levels on androgen levels—may explain why hormonal birth control can impact libido. You can read more about the relationship between birth control and sex drive here and here.
SHBG and the pill, the patch, and the vaginal ring
Birth control that contains estrogen (the combined pill, the contraceptive patch, and vaginal ring) increases levels of SHBG (14,16-19). (In these cases, the increase in SHBG is caused by the estrogen contained in these forms of birth control (14,20).
SHBG and the hormonal IUD, implant, injection, and minipill
Progestin-only forms of birth control (the hormonal IUD, etonogestrel implant, the DMPA contraceptive injection (shot), and the levonorgestrel mini pill) have been shown to decrease SHBG (21-25).
SHBG, hormonal birth control, and blood clots
Also, SHBG levels may be an informative indicator for risk of blood clot while using hormonal birth control (26,27).
Among combined hormonal birth control users, higher SHBG levels are associated with increased risk of blood clot.
This association is probably not causal—that is, SHBG doesn’t cause an increased risk in blood clot. Rather, the association is probably driven by the relationship between both these things and estrogen.
Estrogen from the combined hormonal contraceptive increases SHBG levels (9,14), and the amount of estrogen in birth control is also thought to increase the risk of blood clots among hormonal birth control users (28).
What else should I know about SHBG?
SHBG levels appear to have an effect on breast health. For instance, in studies of premenopausal women who were not using birth control, higher SHBG levels corresponded to higher fluid levels in breasts (29).
Relatedly, the risk of postmenopausal breast cancer may be lower among those with high levels of SHBG, in comparison to those with low levels of SHBG (30). Also, weight loss and use of some breast cancer treatments, like tamoxifen, may decrease the risk of breast cancer by increasing the levels of SHBG (5,31,32). Higher levels of SHBG may be beneficial because SHBG binds to estrogen, thus reducing the ability of estrogen to promote cancer growth (5,31). Also, SHBG may impact cancer growth directly (32).
Higher levels of SHBG have also been associated with better cardiovascular health and metabolic status in postmenopausal women (33,34).
Although SHBG is mostly known for its affect on sex hormones, future research may show that it has its own specific role to play in our bodies.
