People living with diabetes should consider the use of either female or male hormones during their lifetime to improve quality of life, however, many factors need to be considered. Dr Louise Johnson walks us through these factors, explaining diabetes and sex hormones.

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Women and sex hormones

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In the reproductive years, a female should consider contraception methods (sex hormones) to prevent unplanned pregnancies. The risk of unplanned pregnancies has a possibility of miscarriage and foetal abnormalities if the HbA1c (average 3-month glucose value) is not at a normal or near normal value. The HbA1c should be 6 to 6,5% to promote developing a healthy baby.

The menstrual cycle

During a 28-day cycle, there are two different hormones, oestrogen and progestogen, at play that prepare the ovaries to produce an egg, which can then be fertilised should it encounter sperm.

The cycle starts off with the follicle of the ovary secreting oestrogen so that the endometrium (inside of the uterus lining) increases rapidly in thickness, from the 5^th to the 14^th day of the menstrual cycle. This is where blood vessels grow in preparation of a possible egg cell. This is called the proliferative phase.

On day 14, ovulation occurs and the egg cell is secreted from the ovaries. The blood vessels are then on its thickest, under the influence of oestrogen. Should there be no implantation of a fertilised egg cell and sperm, the hormonal support begins to be withdrawn. This causes the inner layer of the uterus to be necrotic, and then bleeding of the inner wall occurs, known as menstruation.

After the bleeding, the endometrium becomes ready again for the proliferative phase, which is the preparation of the lining for possible implantation, which will occur after day 14 in the secretory phase. The secretory phase is constant at 14 days. The variation in the menstrual days is due to the thickness of the layer that formed in the proliferative phase³.

Oral contraceptives

There are two types of contraceptives – local and systemic contraceptives.

Local contraceptive

• An intrauterine device (IUD) is placed inside the womb and can prevent pregnancies. This is a Copper T and does not release sex hormones.
• The intrauterine system (IUS) is placed inside the womb and secretes low-doses of levonorgesterol hormone to prevent pregnancy.
• Implantable contraceptive in arm. It releases a steady dose of progestogen to prevent pregnancy.

Systemic contraceptives

• Progestogen-only tablets or depot injection every eight to 12 weeks. This is usually the safest systemic combination for women: living with diabetes, who smoke, suffer with migraines, are overweight, or have other medical conditions.
• Combination therapy of oestrogen and progestogen.

Choosing the correct method

In deciding which would be the correct method for you, your doctor should take into consideration that it should not interfere with your carbohydrate metabolism or with your lipid profile. The method should not increase long-term microvascular and macrovascular complications.

In a review of literature, it was found that there is currently no one method that is superior to another. The methods should be discussed with the female diabetic patient, where all the pros and cons of each method are understood⁷.

It’s important to remember that only condoms can protect against STDs. Other methods can protect against pregnancy only.

Contraceptives that are more than 99% effective, if used correctly:

• Contraceptive implant – lasts up to three years.
• IUS system – lasts up to five years.
• IUD – lasts up to five to 10 years.
• Female sterilisation – permanent.
• Male sterilisation or vasectomy – permanent.

Contraceptives that are more than 99% effective, if always used correctly but generally less than 95% effective with typical use:

• Contraceptive injection – important to renew strictly every eight to 12 weeks, depending on the type.
• Combination pill – take every day for three weeks out of four weeks. Can skip the red or placebo tablets, if menstruation is wanted to be avoided.
• Progesterone-only pill – take every day.
• Contraceptive patch – renewed each week for three weeks in every month.
• Vaginal ring – renewed once a month.

Contraceptives that are 92 to 96% effective, if used correctly:

• Female condom (every time you have sex).
• Diaphragm with spermicide (every time you have sex).
• Cap with spermicide (every time you have sex).

Factors to consider

• How soon do you want to fall pregnant and is your HbA1c level at target?
• How conscientious are you in taking medication or applications regularly? Do you remember to take tablets on a daily basis? This is vital with the contraceptive pill, since it is not effective if not taken regularly.
• Do you want to menstruate every month or would you prefer a method that takes that away, or alter it causing lighter or sometimes heavier bleeding?
• Do you smoke? Diabetic patients should not be smoking due to the increased vascular risk of atherosclerosis (calcification of blood vessels) of small and large vessels disease, such as eye-, feet-, kidney-, brain- and heart blood vessel damage.
• If you are currently smoking and are over 35 years of age, the combination pill will not be suitable to use due to the possible increase in vascular disease. If you prefer a pill, the progestogen-only pill would be an option, or the IUD, IUS, or contraceptive injection.
• Are you overweight? The contraceptive method that can cause a slight increase in weight is the contraceptive injection, if used for more than two years.
• Do you have additional medical conditions, such as breast cancer? If yes, you are not suitable to use combination hormonal therapy. Other methods, such as IUD, are suitable.
• Do you suffer from migraines? If so, you should be careful when using contraceptives, since it can aggravate this condition. You should use the IUD, IUS, progestogen-only pill, contraceptive injection or implantation. Stay clear from oestrogen preparations.

Hormonal replacement therapy (HRT) in menopause

Usually around 50 years of age, women reach menopause when their ovaries stop producing sex hormones. The symptoms of menopause may differ between women. Some have profuse sweating, palpitations, moodiness, tiredness and insomnia, while others have very little symptoms.

The natural menopause can be divided into three stages:

• Perimenopause – this is the time between the start of the symptoms and up to one year after the final menstruation.
• Menopause is confirmed 12 months after the last menstrual cycle.
• Post-menopause is the years after the menopause.

The replacement of female sex hormones should be carefully evaluated in each person since there are risks associated with this. There are two types of HRT:

• Oestrogen-only therapy (ET): oestrogen is the hormone that provides the most menopausal symptom relief. ET is prescribed for women without a uterus (womb) due to a hysterectomy.
• Oestrogen plus progestogen therapy (EPT): the progestogen is added to the oestrogen therapy to protect the uterus against endometrial cancer (womb cancer) from oestrogen alone.

Diabetic women and HRT

The diabetic women with symptoms severe enough to require systematic hormones should be started on the lowest effective dose for the shortest amount of time.

The benefit-risk ratio is favourable for women who initiate HRT close to menopause (ages 50-59 years) but the benefits becomes riskier with time from menopause and advancing age.

Women with early menopause (before 40 years of age) without a family history of breast cancer can take HRT until the typical age of menopause at 51.

Your doctor will evaluate your risks and possible benefits since there is no ‘one size fits all’ therapy.

Benefits of HRT

Improvement of symptoms of hot flashes, vaginal dryness, night sweats, and bone loss which can lead to osteoporosis. These benefits can lead to improved sleep, sexual relations and quality of life.

Risks of HRT

The importance of low-hormonal dosage for a short period of time cannot be reiterated enough. In the Women’s Health Initiative (WHI), done in 2002, an evaluation was done on the side effects of HRT. It was shown that there was an increased risk of breast cancer. Also, an increased risk of blood clots in the veins were shown, known as deep venous thrombosis (DVT) and pulmonary embolism (PE). The risks were higher in women older than 60 years of age.

Women who still have their uterus, should be prescribed a combination of oestrogen and progestogen to protect against uterine cancer.

Remember, there are other options available to help with hot flashes and moodiness other than sex hormones. Certain antidepressants, such as Venlafaxine and Clonidine, can help with vascular symptoms of hot flashes.

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Men and sex hormones

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Sexual dysfunction in Type 2 diabetes

The most common presentation of Type 2 diabetes with sexual dysfunction is erectile dysfunction (ED), also called impotence.

ED is defined as the inability to sustain adequate penile erection for satisfactory sexual activity. It is common in adult men with Type 2 diabetes (50-75%). This has a negative impact on quality of life. ED has been described in up to a third of newly diagnosed men with diabetes¹.

Low testosterone levels in men have been shown to predict insulin resistance and the future development of Type 2 diabetes⁵. In studies, it was found that hypogonadism (diminished functional activity of testes) in Type 2 diabetic men may be as high as 33%².

Additional risk factors for ED include:

• Duration of diabetes
• Increasing age
• Poor glycaemic control
• Cigarette smoking
• Hypertension
• High cholesterol
• Cardiovascular disease

ED in diabetic men

ED occurs 10-15 years earlier in men with diabetes. It is more severe and less responsive to oral drugs than in non-diabetic subjects.

It is important to tell your doctor if you suffer from ED since it is associated with an earlier risk for cardiovascular disease. The risk for cardiovascular disease, such as heart attacks, is 20% higher in low-testosterone groups.

In the Copenhagen City Heart Study, it was shown that a low testosterone level could increase the risk of stroke with 34%, compared with normal testosterone individuals⁶.

Screening with an effort ECG will help to identify the high-risk individual. The first line of treatment for ED is addressing the risk factors effectively. The first therapeutic option would be to start with a PDE5 inhibitor (Viagra, Cialis, Levitra). A specialist should be consulted for second line therapy, should the patient not respond to these tablets.

Testosterone replacement

It is important to measure testosterone in all adult Type 2 diabetic men since up to 40% will have low levels⁴. It is also important to measure these levels in all patients presenting with ED.

A change in hormonal state is not unique to women. In men, it is called andropause; men will suffer with irritation, aggression, depression, hair loss and, sometimes even, loss in muscle mass.

Hypogonadism or andropause is present when there are symptoms, such as impaired cognitive and sexual functioning, associated depression and low testosterone levels. It is of importance to remember that the testosterone levels should be tested between 7am and 11am, after an overnight fast.

Testosterone therapy is approved for treatment if these factors are present. A trial therapy of three to 12 months is of importance to fully access response.

Types of testosterone replacement

• Tablets (testosterone undecanoate) three to four capsules daily.
• Intramuscular injection every six to 10 weeks. The interval will depend on the response to medication and testosterone levels.

Monitoring of testosterone treatment

It is important to monitor a few parameters after three, six and 12 months of starting therapy. These parameters are:

• Serum testosterone level towards the end of the testosterone interval.
• PSA (prostate specific antigen).
• Haematocrit (red blood cell count).
• Regular examination of the prostate.

The evaluation of the prostate, before and during treatment, is important because of concerns that exist between prostate cancer and testosterone therapy.

The importance of measuring the haematocrit is that testosterone can increase the haematocrit in some individuals and they then have an increase risk in cardiovascular events. The haematocrit should stay below 54%. If treatment is needed and this value continues to be above 54% then the person should have regularly phlebotomies (donating of blood for medical purposes).