Gab Kovacs1 and Paula Briggs2
(1)
Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia
(2)
Sexual and Reproductive Health, Southport and Ormskirk Hospital, Southport, UK
Hormonal
Combined Hormonal Contraception: Pills, Patches and Vaginal Rings
Progestin Only Methods: These Include Pills, Implants, Injections and Intrauterine Systems
Emergency Contraception
Non-hormonal
Barriers
CuIUD
Natural Family Planning (NFP)
Sterilisation (Male and Female)
Hormonal
Combined Hormonal Contraception: Pills, Patches and Vaginal Rings
Introduction
These are methods containing two sex steroid hormones; an oestrogen and a progestin.
Table 15.1
Classification of contraceptives
|
Abbreviation |
Contraceptive methods |
|
|
LARCs |
Long acting reversible contraception |
Subdermal implants |
|
Intrauterine LNG system Injectable progestin |
||
|
MARCs |
Medium acting reversible contraception |
Vaginal ring |
|
Patches |
||
|
SARCs |
Short acting reversible contraception |
COC |
|
Condoms |
||
|
NARCs |
Not actually reliable contraception |
Diaphragms |
|
Diaphragms |
||
|
Natural methods |
||
All sex steroid hormones are derived from cholesterol and both oestrogens and progestins share a structural similarity.
Oestrogens are characterised by a C18 carbon skeleton.
The early “pills” all contained the synthetic oestrogen – ethinyl oestradiol (EE), or mestranol (which is metabolised to EE), but there are two newer combined oral contraceptives (COCs) which contain “natural” oestrogen, Qlaira® (oestradiol valerate/dienogest in a variable dosing regimen) and Zoely® (oestradiol/nomegestrol acetate).
Progestins are characterised by a C21 carbon skeleton.
Progestogen is a hormone with a progestational effect on the endometrium, and synthetic progestogens are called progestins.
It is important to remember that as all sex steroid hormones share the basic “chicken wire” structure, it is possible for the hormones to “morph” between structural forms, hence sharing specific features of the different sex steroids (Fig. 15.1).
Fig 15.1
Basic steroid hormone structure
Naturally occurring progesterone interacts with the progesterone receptor in a “key in a lock fashion”. Synthetic progestins interact in a “less perfect fit fashion”. They also interact with other hormone receptors, either blocking or stimulating these receptors. These include all other steroid receptors, namely oestrogen, androgen, mineralocorticoid and glucocorticoid.
During the last 55 years, the progestins in COCs have been refined to maximize efficacy, and minimise side effects. They have been categorised into “generations”.
First Generation Progestins
Norethisterone is a first generation progestin, still used frequently today for contraception and to manage gynaecological problems.
Norethisterone also stimulates the oestrogen receptor to some degree, giving it an oestrogenic profile.
Second Generation Progestins
Norgestrel was developed as a more potent progestin. This meant that smaller amounts could be used, to achieve the desired effect, hence minimising potential side effects. It is 20–30 times more potent, weight for weight than norethisterone. Initially a mixture of d and l isomers were used. However, as only the levo (Levonorgestrel) form is orally active, using this alone enabled the amount of hormone administered to be reduced by 50 %, thus potentially further reducing side effects.
Third Generation Progestins
These include, Desogestrel, Gestodene and Norgestimate.
These progestins have minimal androgenic activity, with a more favourable effect on lipid profile and are twice as potent as levonorgestrel. They provide high efficacy with less side effects, but have been tainted by the venous thromboembolism (VTE) controversy of 1995.
Fourth Generation Progestins
This group are in a class of their own, being derived from 17 alpha spironolactone and having a mild diuretic effect. This helps to reduce the fluid retaining effect of oestrogen when used in a COC. The pharmacological action of drospirenone is similar to progesterone and there is no androgenic activity associated with this synthetic hormone. Drospirenone blocks the androgen receptor – i.e. it is anti androgenic and in addition has anti-mineralcorticoid effects as described above. This reduces the risk of common side effects associated with taking the COC occurring, namely bloating, weight gain and acne.
Cyproterone Acetate
This synthetic steroid hormone stimulates the progesterone receptor and also blocks the androgen receptor. In the UK, a combination of 35 micrograms of ethinyl oestradiol and 2 mg of cyproterone acetate (Dianette®) is licensed as a treatment for acne, but not as a method of contraception. However, it is known to be, and is used as, an effective method of contraception.
There are two regimens available for COC- monophasic and multiphasic.
In monophasic pills the same combination of oestrogen and progestin is administered every day for 21–24 days, followed by a pill free period of 4–7 days, during which time the woman gets a withdrawal bleed. Some women prefer to not have these bleeds and run the cycles together, “tailored pill taking”. In the United States, commercially packaged preparations with a reduction in the hormone free interval are available. A combination of drospirenone and ethinyl oestradiol (3 mg/20 ug) (YazFlex®) is available in a flexible extended regimen, allowing the woman a choice of when she bleeds. During days 25–120 a woman may decide to take a 4-day tablet-free break, but not before day 24. A tablet-free interval should not be longer than 4 days. A 4-day tablet free interval has to be taken after 120 days of continuous tablet-taking. YAZ Flex can only be used in combination with a dedicated CLYK tablet dispenser.
Multiphasic pills contain different concentrations of oestrogen and progestin over 21–26 days, with placebo pills making up the remainder of the 28 day pack in some preparations. This reduces the total amount of hormone administered and may improve cycle control. The quadra-phasic preparation Qlaira® has an additional license for the treatment of HMB in women requiring contraception.
Patches contain EE and Norelgestromin (Evra®) and are applied once a week, in a 3 weeks “on”, 1 week “off” regime.
Vaginal ring (Etonogestrel/ EE; Nuvaring®) are inserted for 3 weeks, with a ring free week resulting in a withdrawal bleed.
Patches and vaginal rings have the same mode of action as the COC (inhibition of ovulation), and the same contraindications. The advantages include non-daily delivery, and avoidance of the entero-hepatic circulation. Direct absorption of the hormones into the systemic circulation, theoretically improves cycle control.
Mechanism of Action
Combined hormonal contraceptives have three modes of action:
1.
2.
3.
Eligibility
The Faculty of Sexual and Reproductive Healthcare (FSRH), has developed the Medical Eligibility Criteria (UKMEC) for contraceptive use:
· Category 1: there is no restriction for use.
· Category 2: the advantages of using the method out way risk.
· Category 3: referral to a specialist contraceptive provider may be indicated as the associated risk may out way any advantage of using the method.
· Category 4: indicates that the risks outweigh the benefits and the method should not be used.
For CHC MEC 3 and 4 conditions include: Obesity, smoking more than 15 cigarettes per day over the age of 35, VTE past or current, known thrombogenic mutations, hypertension (systolic >160, diastolic >95), ischaemic heart disease, complicated valvular congenital heart disease, history of stroke or TIAs, migraine with aura, diabetes with vascular complications, breast cancer, severe liver disease, SLE with antiphospholipid antibody, Raynauds with lupus anticoagulant, planning major surgery and the concomitant use of enzyme inducing medication.
These apply to all CHCs – pills patches and rings.
Efficacy
Efficacy reflects how well fertility is controlled by a method of contraception. The failure rate is the sum of the method failure plus user failure i.e. failure rates with perfect and typical use. With the COC perfect use failure rates are low and may be associated with malabsorption or drug interactions. On the other hand, typical user failure rates are quite high due to women forgetting to take their pills. Overall the failure rate including both perfect and typical use, for CHC is approximately 9 %.
Side Effects
Serious side effects include venous thrombo embolism (VTE) – deep vein thrombosis (DVT) and pulmonary embolism (PE) and arterial thrombosis. The risk of VTE in COC users is approximately twice that in a comparable population not taking the “pill”- 9–10/10,000 vs 4.4/10,000 per year. The risk is highest in the first 3 months. There are specific risk factors, which can increase the likelihood of a cardiovascular event occurring – these include migraine with aura, hypertension and smoking over the age of 35. Use of CHC is a co-factor for cervical cancer. COCs appear to have little effect on the risk of breast cancer.
Nuisance side effects reported by women include weight gain, breast tenderness, acne, nausea and mood changes. Although these side effects are not life threatening, they may result in women discontinuing their contraceptive method and therefore should not be dismissed lightly.
Non-contraceptive Benefits
The most important non-contraceptive benefit of the COC is its effect on the menstrual cycle. It regulates bleeding, allowing a woman to choose if and when she bleeds and blood loss is reduced by approximately 40 % with a corresponding reduction in dysmenorrhoea. There is also a significant decrease in ovarian and uterine cancer in COC users. Because ovulation is suppressed, functional ovarian cysts (follicular and luteal) occur less frequently. Acne usually improves with the use of CHCs, especially if anti-androgenic progestins are used.
Progestin Only Methods: These Include Pills, Implants, Injections and Intrauterine Systems
Introduction
Progestin only methods have none of the risks associated with the use of oestrogen, as described above. There are very few contraindications. The disadvantage is, that in contrast to CHC, they do not provide good cycle control, and irregular bleeding and/or amenorrhoea are common. This may result in some women discontinuing the method.
Mechanism of Action
The primary action of progestins is to make the cervical mucous thick and impenetrable by sperm. Some progestins also inhibit ovulation by suppressing the LH surge.
Progestogen only pills (POP) – also called “mini-pills”
The first and second generation POPs acted mainly by their cervical mucous effects, although more than half of the cycles were anovulatory. This necessitated that each tablet was taken within a 3 h window.
In the UK a third generation POP is available containing desogesterel, which inhibits the LH surge and ovulation. It has a 12 h window, which is reflected in an decrease in failure rate.
Progestins can be administered by injection either intramuscularly (depot medroxyprogesterone acetate (DMPA- DepoProvera®)) 150 mg, or subcutaneously (Sayana Press®; 104 mg/0.65 ml MPA) every 12 weeks. MPA inhibits folliculogenesis by suppressing the release of gonadotrophins, thus inducing a hypo-oestrogenic state.
The subdermal progestogen only implant (SDI) contains etonogestrel impregnanted in a ethinyl vinyl acetate polymer with a rate limiting membrane, which secretes a small amount of hormone into the circulation each day (60–70 ug/day initially, decreasing to half that by end the third year), for 3 years. Its primary mode of action is ovulation inhibition (suppression of the LH peak), but there is still some follicular development, resulting in oestrogen levels in the mid follicular range. This is in contrast to the injectables, where oestrogen levels are suppressed, with no folliculogenesis in some women and a potential for reduction in bone mineral density. Progestogen only implants have secondary effects on cervical mucous and the endometrium, making it thin and non-receptive.
Levonorgestrel releasing Intra Uterine System (LNG-IUS)
There are two available options with different doses of levorgestrel released daily – 20 micrograms (Mirena®), licensed for up to 5 years or 12 micrograms (Jaydess®), licensed for use up to 3 years.
An IUS is fitted like an IUD, but that is the end of the similarity. Both intrauterine systems release progestin directly into the endometrial cavity, causing atrophy, which prevents implantation and reduces bleeding. They have a negative effect on sperm penetration through the cervical mucous. There is no effect on the hypothalamo-pituitary axis, and most women continue to ovulate.
Eligibility
These methods are suitable for women who cannot take oestrogen and consequently there are fewer contraindications.
These include the presence of unexplained vaginal bleeding, and for intrauterine methods, pelvic inflammatory disease including TB, cervical or endometrial cancer, the presence of gestational trophoblastic disease and distortion of the endometrial cavity.
Nuliparity is not a contraindication to the use of intrauterine contraception.
Efficacy
All long acting reversible contraceptive (LARC) choices, reduce user failure. These methods are described as “fit and forget”.
The injectable has a higher typical failure rate, as women need to attend 3 monthly for their injection.
The LNG-IUS and SDI have no user failure once inserted, and are effective for 5 and 3 years respectively, with less than 1 % failure per year.
Side Effects
The most common “side effect” for progestin only methods is unscheduled bleeding. With injectables (DMPA/MPA) up to 70 % of users are amenorrhoeic by 1 year of use. Some women experience weight gain whilst using injectable progestins, but there is no evidence to support weight gain for women using the POP, a SDI or IUS. There is no evidence for a causal relationship between the use of progestins and mood change, loss of libido or headaches. There is no causal relationship between progestin only contraception and cardiovascular disease, venous thromboembolism or breast cancer. However, women using injectable progestins may have a reduction in bone mineral density, which recovers when the method is stopped.
Non Contraceptive Benefits
Progestins reduce bleeding. They also alleviate dysmenorrhoea, and have a beneficial effect on endometriosis.
The use of the LNG-IUS has revolutionised the treatment of HMB, virtually eliminating the need for surgical treatment due to a 90 % reduction in bleeding on average after 12 months. Mirena® has a license to treat heavy menstrual bleeding.
Emergency Contraception
Introduction
Post-coital contraception has been used to try and prevent pregnancies for many decades. Originally high dose norethisterone (50 mg) was administered with the aim of disrupting the endometrium and preventing implantation. The Yuzpe regimen of four 50 μg COCs taken within 72 h of coitus followed, but the side effects associated with such high oestrogen doses was poorly tolerated. The use of levonorgestrel 1500 ug is now widely available, and ulipristal acetate (UPA) 30 mg in a stat dose is also available in many countries. UPA is three times as effective as LNG. It can still delay or inhibit ovulation, even if the LH surge has already started.
The most effective method of emergency contraception is a copper IUD. This is effective up to 120 h after unprotected sex and can also be fitted up to 5 days after the predicted day of ovulation in a regular cycle. In addition to emergency contraception a CuIUD also provides ongoing contraception for up to 10 years.
Mechanism of Action
Levonorgestrel (LNG) is thought to act by inhibiting the LH peak, and delaying or preventing ovulation. UPA also principally works by inhibiting ovulation, but there is evidence that it still has some effect after the LH surge has started. Whilst it has some effect on the endometrium, there is no evidence to suggest that it prevents implantation.
The copper IUD is toxic to the ovum and sperm, inhibiting fertilization, but it also has an anti-implantation effect. There is no evidence that the LNG-IUS is effective for emergency contraception.
Eligibility
There are no contraindications to the use of LNG for emergency hormonal contraception. The dose should be doubled for women taking an enzyme inducing drug (out of product license).
UPA should be avoided if there is a pre-existing risk of pregnancy, the woman is taking an enzyme inducing drug or is breast feeding.
Efficacy
The most effective method of EC is the insertion of a Cu IUD within 5 days or up to 5 days after the predicted day of ovulation. Pregnancy rates are thought to be less than 1 %.
Comparative studies have shown a trend for greater effectiveness for UPA. Although LNG is licensed to be used up to 72 h after UPSI, historically it was used up to 120 h. There is a sixfold increase in the risk of pregnancy between 96 and 120 h. UPA is licensed to be used up to 120 h and there is no change in efficacy during that time.
Side Effects
Insertion of an IUD may be accompanied by discomfort. At the time of insertion of intrauterine contraception, there is a sixfold increase in infection in the first 20 days, a risk of expulsion and a risk of perforation of the uterus (2/1,000).
The use of LNG or UPA can be associated with headache, nausea (less than 20 % of users), abdominal pain, dizziness, and an altered bleeding pattern.
Non-contraceptive Benefits
None.
Non-hormonal
Barriers
Introduction
Condoms have been in common usage for several centuries. Initially animal intestines and treated linen were used to prevent infection as well as pregnancy. Rubber condoms became available in the nineteenth century, and latex in the twentieth century.
Mechanism of Action
The mechanism of action of barrier contraception is to separate the sperm from the ovum. Barriers can be separated into male methods – condoms and female methods – diaphragms and female condom.
Eligibility
Virtually any couple can use a barrier method. Latex free condoms are available for people with latex allergies. Newer diaphragms do not require expert fitting but the user has to be comfortable with insertion and removal and with the use of a spermicide.
Efficacy
An intact condom, properly used, is an effective method of contraception. Proper usage requires no genital contact, application onto an erect penis with no air bubble in the teat, withdrawal immediately on ejaculation, and safe disposal of the condom. Should a condom break or come off during sexual intercourse, emergency contraception should be used.
Female barrier methods are less reliable. Studies have reported around 20 % pregnancy rates for users per year
There are no side effects. Condoms may be a problem for an aging male who has difficulty maintaining an erection.
Non-contraceptive Benefits
A great advantage of condoms is that an intact condom will decrease the risk of transmission for many infections.
CuIUD
Introduction
The first CuIUD to be used was the Grafenberg ring, which was introduced in 1929. It consisted of a copper spring wound into a coil. It had to be inserted with a hook, which pushed it into the uterine cavity, and it was “fished out blind”, when it was time for removal! This was followed by a series of plastic IUDs, the most notorious of which was the Dalkon Shield, which resulted in a number of deaths, due to pelvic infection, because of the multifilament tail, which was thought to be a vehicle for organisms to reach the uterine cavity. These inert IUDs have now been superseded by copper or medicated devices.
Mechanism of Action
Copper is toxic to both sperm and the ovum. Its primary action is to prevent fertilisation. It also has a toxic effect on the endometrium, inhibiting implantation, as well as having a negative effect on the cervical mucous to inhibit sperm penetration.
Eligibility
Contraindications include introduction of a CuIUD in the presence of unexplained vaginal bleeding, pelvic inflammatory disease including TB, cervical or endometrial cancer, or continuing use in the presence of gestational trophoblast disease. Uterine fibroids disrupting the endometrial cavity, or an anatomical abnormality of the uterus are relative contraindications to insertion. CuIUDs can be used in nuliparous women.
Efficacy
There are many copper IUDs on the market. In the UK there are 14 different models, licensed for use for between 5 and 10 years. After 5 years follow up pregnancy rates of less than 2 % are reported.
Side Effects
The most sinister side effect following insertion of an IUD is pelvic inflammatory disease (PID). The risk of PID is increased sixfold during the first 20 days after insertion. Complications of insertion such as perforation are rare (2/1,000), but expulsion is more common (1 in 20 women), most commonly during the first 3 months after insertion.
Non-contraceptive Benefits
None
Natural Family Planning (NFP)
Introduction
There are couples who do not want to use hormonal, chemical or mechanical contraception, and who wish to use natural methods to avoid pregnancy. These methods aim to avoid sexual intercourse around the time of ovulation. Sperm may live for several days within the cervical mucus, and couples require strong will power during this time.
Mechanism of Action
The estimation of the time of ovulation is the main basis of NFP.
This can be done based on cycle rhythm (rhythm method), changes in body temperature, or by studying changes in the cervical mucus through the cycle (Billings method).
The rhythm method works on the basis that the luteal phase is usually about 14 days long, so that if one subtracts 14 days from the longest cycle and from the shortest cycle during the last 6 months, then the range of ovulation days can be predicted. The couple should then abstain from sexual intercourse for 4–5 days before the earliest possible day (to allow sperm to die), until after the latest day. The problem is that we are predicting ovulation on the basis of past cycles, and there is no guarantee that there may not be variation.
The temperature method relies on the thermogenic effect of progesterone. After ovulation the basal body temperature rises about 0.4 of a degree. A woman needs to take her temperature every morning on wakening, and when she detects a significant rise, she can presume she has ovulated. Again, the couple need to abstain for several days before the temperature rise, until there is persistent elevation of the body temperature. This method at least actually detects presumed ovulation, rather than estimating it.
The Billings method based on the mucous changes is a “bio-assay” of the menstrual cycle. This was discussed in Chap. 1, but the principle is that a woman predicts when her follicles are ripening, abstains from sexual intercourse until signs of ovulation have been noted when the couple can resume having sexual intercourse.
Eligibility
There are no medical contra-indications to the use of NFP. However, couples for whom an unplanned pregnancy would cause serious problems, should be encouraged to use a more reliable method of contraception.
Efficacy
Whilst the principles of NFP are valid, it requires strong willpower and user compliance for it to be effective. Some clinical trials have reported efficacy rates above 90 % but widespread use has a much higher failure rate.
Side Effects
None
Non-contraceptive Benefits
Women who wish to conceive can use the principles of NFP in reverse to help time when sexual intercourse is most likely to result in pregnancy.
Sterilisation (Male and Female)
Introduction
Sterilisation literally means “to make sterile”. It is only an option for couples who have completed their families and are 110 % certain they do not want any more children.
Mechanism of Action
In women, it is usually accomplished by obstructing the fallopian tubes. Originally this required surgical ligation (known as tubal ligation), but with the introduction of laparoscopy to gynaecology, simpler options such as burning the tubes or applying clips and rings were developed. The most popular method today is applying Filshie clips (titanium and silastic) to the mid isthmus part of the tube under laparoscopic vision.
A hysteroscopic method of sterilisation (Essure®) is available. This involves the insertion of a self expanding microcoil containing Dacron fibres, which results in fibrosis and obstruction of the isthmus over 3 months, during which time on going contraception is required. In contrast to laparoscopy, which is usually performed under general anaesthetic, Essure® can be inserted as an outpatient.
In men sterilisation requires vasectomy – disruption of the vas deferens. It can be done under local anaesthetic as an outpatient procedure. The newer non- scalpel technique is associated with a lower failure rate and fewer complications.
Eligibility
Anyone can be sterilised, but the aim is to avoid regret. Couples may require counselling.
Efficacy
There is a failure rate associated with sterilisation. Following vasectomy semen analysis is required to ensure azoospermia after 10–15 ejaculations. Re-canalisation is very rare, and method failure is less than 1 %.
The failure rate with Filshie clip sterilisation is about 5 per 1,000 operations.
Side Effects
Both female and male sterilisation cause no changes except for preventing the passage of sperm or ova. There is no reason why any other side effects should occur.
Both techniques can have operative complications. Vasectomy may be associated with haemorrhage and haematoma, or very rarely infection. Occasionally a granuloma may result at the operative site.
For laparoscopic sterilisation there are the usual although infrequent complications. These include anaesthetic problems (1:10,000), trauma to organs or blood vessels (1 in a 1,000) and gas embolism.
Non-contraceptive Benefits
In some couples the fear of pregnancy causes stress. For these couples having an effective method of contraception may improve their general well being.