COMBINED ORAL CONTRACEPTIVES Mechanism of action
The combined oral contraceptive (COC) pills currently available in the UK are shown in Table 2. They combine an estrogen (ethinylestradiol (EE) in all cases but one) with one of seven progestogens. Aside from secondary contraceptive effects on the cervical mucus and to impede implantation, COCs primarily prevent ovulation. This makes the method highly effective in ‘perfect’ use (Table 1), but it removes the normal menstrual cyle and replaces it with a cycle that is user-produced and based only on the end-organ, i.e. the endometrium.
The text of this manual, an update of the second edition of our Concise Guide
to Women’s Mental Health, reflects the latest data on women’s mental health.
Although every section has been revised, particularly extensive revisions have
been made in the sections describing the use of psychiatric medications in pregnant
and breast-feeding women, abortion and contraception, and the use of
hormones in menopausal women. The book continues to reflect our expanding
clinical experiences in the Women’s Life Center.
Contraceptive methods can be divided into two subgroups as hormonal and non-hormonal.
Hormonal contraceptives include combined-oral contraceptives, progestin only pills,
hormonal implants, progestin releasing intrauterine systems, depomedroxyprogesterone
acetate injections, and vaginal rings. Non-hormonal contraceptive methods include male and
female condoms, copper intrauterine device, tubal ligation and vasectomy of the companion.
Combined oral contraceptives are a widely used and well accepted form of contraception.
For the purposes of excluding pregnancy, the CEU would advise that hormonal, intrauterine
and barrier methods can be considered reliable providing they have been used consistently
and correctly on every incidence of intercourse. This should be assessed on an individual
Quick starting may also mean starting a method immediately after the administration of
emergency contraception (EC). In this situation there is a possibility of EC failure and
pregnancy, therefore such practice would always be outside the licence of hormonal
When starting hormonal contraception after POEC (Levonelle 1500® or Levonelle One Step®)
additional contraception should be advised until contraceptive efficacy is established (see
Summary on page iv).
There are no data on quick starting hormonal contraception after use of the emergency
contraceptive, ulipristal acetate (UPA) (ellaOne®). As UPA is a progesterone receptor
modulator that blocks the action of progesterone, it may affect the contraceptive efficacy of
hormonal methods.35,36 However, no interaction studies have been carried out to date.
A Cochrane review has found limited evidence that immediate (‘quick’) start of hormonal
contraception reduces unintended pregnancies or improves continuation rates.15 None of
the studies included in the review were powered to detect contraceptive efficacy. Whilst
there is currently a paucity of evidence demonstrating effectiveness, there are data to
suggest women find quick starting acceptable.
It is possible that effectiveness may vary depending on method type.
The half-life of UPA is 32.4 hours, which means that most of the drug is eliminated by 1 week
and the interaction with hormonal contraception is likely to be clinically insignificant by this
time. If a hormonal method is quick started the CEU advises use of additional contraceptive
precautions for 1 week after taking UPA plus the time required for contraceptive efficacy to
be established (see Summary on page iv).
On the federal level, three agencies regulate ART. The Centers for Disease Control
and Prevention (CDC) collects and publishes data on ART procedures. The Food
and Drug Administration (FDA) controls approval and use of drugs, biological
products, and medical devices and has jurisdiction over screening and testing of
reproductive tissues, such as donor eggs and sperm. The Centers for Medicare and
Medicaid Services (CMS) is responsible for implementation of the Clinical
Laboratory Improvement Act to ensure the quality of laboratory testing....
Inadvertent fetal exposure to contraceptive hormones is common, with a USA study
estimating that approximately 70 000 fetuses are exposed to oral contraceptives annually.23
Most of the data on fetal outcomes relate to COC. The CEU found no studies that specifically
assessed exposure through quick starting contraception. Studies are often limited by their
observational nature, potential confounding factors and small sample size. Reassuringly there
have been no consistent findings of specific fetal abnormalities.
Estrogen acts as a proconvulsant in several animal models of epilepsy, including amygdalal
kindling and pentylenetetrazol administration in ovariectomized rats (Hom and
Buterbaugh, 1986). Estrogen induces the formation of new excitatory synapses in the CA1
region of the hippocampus; and further, this estrogenic induction involves activation of Nmethyl-
Daspartate (NMDA) receptors (McEwen, 2002). Increasing the complexity of
hippocampal synaptic density is likely a mechanism for the proconvulsant activity of
The appropriate time to start contraception depends on the contraceptive method and may
also depend on medical and social factors. Traditionally, initiation of hormonal and
intrauterine methods of contraception has been delayed until the onset of the next menstrual
period in order to avoid inadvertent use during pregnancy. Starting early in the cycle also
avoids the need for additional contraception. The manufacturers’ Summaries of Product
Characteristics (SPCs) vary in their advice on contraceptive start dates and the need for
Approach to the Patient: Hepatocellular Carcinoma
History and Physical
The history is important in evaluating putative predisposing factors, including a history of hepatitis or jaundice, blood transfusion, or use of intravenous drugs. A family history of HCC or hepatitis should be sought, and a detailed social history taken to include job descriptions for industrial exposure to possible carcinogenic drugs as well as contraceptive hormones.