Endocrine and reproductive systems

Question 1

What is the indication for metformin?

Answer 1

T2D, as first line medication for control of blood glucose, used alone or in combination with other oral drugs or insulin.

Question 2

What is the mechanism of action of metformin?

Answer 2

Metformin is a biguanide that lowers blood glucose by increasing the sensitivity of cells to insulin.

It suppresses hepatic glucose production (glycogenolysis and gluconeogenesis), increases glucose uptake and utilization by skeletal muscle and suppresses intestinal glucose absorption.

It does not stimulate pancreatic insulin secretion and therefore does not cause hypoglycemia.

It reduces weight loss, which can prevent worsening of insulin resistance and slow deterioration of diabetes mellitus.

Question 3

Why does metformin not cause hypoglycemia?

Answer 3

It does not stimulate pancreatic insulin secretion, it works by suppressing hepatic glucose production (glycogenolysis and gluconeogenesis), increases glucose uptake and utilization by skeletal muscle and suppresses intestinal glucose absorption.

Question 4

What is the most common side effect of metformin and how can it be overcome?

Answer 4

Causes GI upset, can be overcome by taking with or after food or by changing to MR release formulation.

The GI upset can contribute to weight loss in patients taking metformin.

Lactic acidosis is a rare adverse effect associated with metformin use, which can be fatal if left untreated.

Question 5

In what cases is metformin contraindicated?

Answer 5

Metformin is excreted unchanged by the kidney, therefore it is contraindicated in severe renal impairment and a dose reduction is required for patients with moderate renal impairment.

Metformin should be withheld where there is acute kidney injury, e.g. in sepsis, shock, or dehydration or severe tissue hypoxia.

Metformin should be withheld during acute alcohol intoxication, when it may precipitate lactic acidosis, and be used with caution in chronic alcohol overuse, where there is a risk of hypoglycaemia.

Question 6

What do prednisolone, thiazide-like and loop diuretics have in common?

Answer 6

All elevate blood glucose, and hence oppose the actions and reduce the efficacy of metformin.

Question 7

Why should patients be advised to tell a doctor that they are taking metformin before having an X-ray or operation?

Answer 7

Metformin must be withheld before and for 48 hours after injection of IV contrast media (e.g. for CT scans, coronary angiography) when there is an increased risk of renal impairment, metformin accumulation and lactic acidosis.

Question 8

Why can insulin and sulphonylureas worsen diabetes mellitus over the long term?

Answer 8

Insulin is an anabolic hormone, it and drugs which increase insulin secretion (e.g. sulphonylureas) cause weight gaine, which can worsen diabetes mellitus in the long term.

Question 9

What are the two indications for oestrogens and progestogens?

Answer 9

1. For hormonal contraception in women who require highly effective and reversible contraception, particularly if they may also benefit from its other effects, such as imporved acne symptoms with oestrogens.
2. For hormone replacement therapy (HRT) in women with early menopause (when it is given until 50 years of age) and those who have distressing menopause symptoms.

Question 10

An improvement in acne symptoms is a benefit of treatment with which hormonal contraception?

Answer 10

Oestrogens.

Question 11

How do oestrogens and progesterones work as contraception?

Answer 11

Luteinising hormone (LH) and follicle-stimulating hormone (FSH) control ovulation and ovarian production of oestrogen and progesterone.

In turn, oestrogen and progesterone exert predominantly negative feedback on LH and FSH release.

In hormonal contraception, an oestrogen (such as ethinylestradiol) and/or progestogen (e.g. desogestrel) are given to suppress LH/FSH release and hence ovulation.

Question 12

What type of contraception is ethinylestradiol? How does it work as a contraception?

Answer 12

Ethinylestradiol is an oestrogen and works to suppress LH/FSH and hence ovulation.

Question 13

What type of contraception is desogestrel?

Answer 13

Desogestrel is a progestogen.

Question 14

Oestrogens and progestogens also have effects outside of the ovary, what are these?

Answer 14

Effects on the cervix and endometrium may contribute to their contraceptive effect (this is especially important in progestogen only pills).

Some cause reduced menstrual pain and bleeding, and improvements in acne (oestrogens).

Question 15

All forms of oestrogens and progestogens are contraindicated in patients with what?

Answer 15

Breast cancer

Question 16

Why should combined hormonal contraception be avoided in patients at an increased risk for VTE? what would constitute being ‘at an increased risk for VTE’?

Answer 16

The oestrogens in the combined hormonal contraceptive products double the risk of venous thromboembolism, VTE, but the absolute risk remains low.

A past VTE or a known thrombogenic mutation would constitute an increased risk for VTE.

Question 17

All forms of combined hormonal contraceptives should be avoided in those with cardiovascular disease, such as what?

Answer 17

If Age >35 years; cardiovascular risk factors; migraine with aura, heavy smoking history.

Question 18

Concurrent use of Rifampicin may reduce the efficacy of the hormonal contraceptive, particularly progestogen-only forms. Why is this?

Answer 18

Rifampicin = cytochrome p450 inducer, increased metabolism.

Most other antibiotics are fine to use.

Question 19

When can COC pills be started in a womans cycle?

Answer 19

COC pills can be started at any day of the cycle. If this is within the first 6 days, no additional contraception is needed. If it is beyond day 6, a barrier method should be used or sex avoided for the first 7 days.