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
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.
Supression of ovulation by inhibition of gonadotrophins- oestradiol principally inhibits FSH, whilst the progestin inhibits the LH rise.
2.
Whilst oestrogen and progesterone are essential for the proliferation and maturation of the endometrium when secreted in a sequential manner, the administration of these hormones in a fixed pharmacological dose throughout the cycle has an anti-endometrial effect, and results in a typical “pill endometrium” which has few glands and does not support implantation of the embryo.
3.
The progestin in CHC has an anti-mucous effect, thus obstructing sperm penetration.
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.
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