Gynaecology & Genitourinary

Conditions:
Menopause

Dr. R. M. Maboa
BSc. MBCHB. DOMH
(Diploma in Occupational Health & Medicine)
Pharmacology & Therapeutics Department
11 February 2020
MBCHB IV
 2

Menopause

 “ defined as the permanent cessation of menstrual periods, determined

retrospectively after a woman has experienced 12 months of amenorrhea without
any other obvious pathological or physiological cause. ”

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3 Menopause

 Functions and unwanted effects of the various oestrogens

 Functions and unwanted effects of the various progestins
 Advantages and Disadvantages of long-term oestrogen therapy
 Alternative drugs for treatment of menopausal symptoms
 Suggest rational HRT for climacteric symptoms and prevention of
osteoporosis

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4 Indications of HRT

 Treatment of menopausal symptoms where the risk:benefit ratio is

favourable, in fully informed women.
 For women with early menopause until the age of natural menopause
(around 51 years), even is they are asymptomatic.
 For those women under 60 years who are at risk of an osteoporotic fracture
in whom non-oestrogen treatments are unsuitable

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5 Premenstrual Syndrome(PMS)
Treatment

 -SSRIs: selective serotonin re uptake inhibitor

 Fluoxetine 20 mg daily is usually sufficient to improve symptoms in most women.
 Side effects such as loss of libido may be partially avoided by administering the
drug only during the luteal phase.
 Cycle suppression:
 Suppression of the cycle can be achieved with Oestrogen ,Danazol , GnRH
agonist analogues or Danazol, even at doses of 200 mg, is particularly effective
for most symptoms of PMS but is limited by masculinizing side effects.

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6 Menopausal hormone therapy=MHT

 “is the broad term used to describe unopposed estrogen (ET)use for
women who have undergone hysterectomy or combined estrogen-
progestin therapy (EPT) for women with an intact uterus who need a
progestin to prevent estrogen-associated endometrial hyperplasia”

 https://www.uptodate.com/contents/treatment-of-menopausal-symptoms-
with-hormone-
therapy?source=search_result&search=menopause%20management&sele
ctedTitle=1~150

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 9 Hot Flashes Management

Mild Moderate to Severe

 Simple behavioural measures:  MHT
 lowering room temperature,  Bazedoxifene/conjugated
 use of fans estrogen =SERM
 Light dressing (((selective estrogen receptor
 avoid triggers (such as spicy foods modulator(SERM) and oestrogen)
and stressful situations)  treatment of postmenopausal
 Weight loss vasomotor symptoms (VMS) and
osteoporosis prevention
 Cognitive behavioural therapy
 Combination of estrogen plus
 Vitamin E intrauterine levonorgestrel
 Hypnosis 2020/02/23
 10 Cont…

 SSRIs/SNRIs/ centrally acting agents

 SSRI= citalopram/escitalopram/paroxetine
 Anti-epileptic drug: gabapentin (@night)
 paroxetine blocks/inhibits the conversion of tamoxifen to active metabolites
endoxifen through CYP2D6, it should not be used in women on tamoxifen.
 SNRI=Desevenlafxine/venlafaxine(minimal inhibition) is an option
 Pregablin
 Clonidine

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 11 High Progestogenes

 Medroxyprogesterone acetate depot without oestrogen

 Mechanism of action: inhibition of gonadotropin secretion inhibits the secretion of gonadotropins which,
in turn, prevents follicular maturation and ovulation and results in endometrial thinning. These actions
produce its contraceptive effect
 Limited data suggest that high doses of progestins may be as effective as MHT for hot flashes
 Norethisterone acetate 10mg po
 Tibolone

 * the long term use of medroxyprogesterone acetate has been associated with osteoporosis

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 12 Benefits of MHT
 Relieve menopausal/ vasomotor symptoms (VSM)
 hot flushes
 Improvement in mood changes
 mood lability/depression
 Improvement of urogenital symptoms
 vaginal atrophy, urinary syptoms
 Improve quality of life
 sleep disturbances (when related to hot flashes)
 joint aches and pains
 Reduction in osteoporosis risk
 ↑BMD-↓fractures
 Reduction in cardiovascular disease
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 ↑HDL ↓LDL
 13 Risk MHT

 Venous thromboembolic (VTE)=Transdermal HRT is preferred in this case instead of

oral.
 Stroke
 Breast cancer-no evidence
 Endometrial cancer-if on estrogen only with intact uterus
 Ovarian cancer-no evidence
 contra-indications for the use of hormone replacement therapy to prevent
osteoporosis:
 Undiagnosed abnormal vaginal bleeding
 Previous pulmonary embolism
 Endometrial cancer
 Acute liver disease 2020/02/23
 14
Menopause=Oestrogen

Hot flushes should be treated with systemic oestrogen

Vulvovaginal atrophy /Genitourinary syndrome of
menopause (GSM) should be treated with low-dose
vaginal estrogen

 Unopposed estrogen use for

women who have undergone
hysterectomy

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15 Menopause=Oestrogen & Progestin

 combined estrogen-progestin therapy (EPT) for women with an intact

uterus who need a progestin to prevent estrogen-associated endometrial
hyperplasia

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 16 Menopause

 Hormone replacement therapy in women with an intact uterus :

 Dydrogesterone/oestrogen: Femoston
 Cyproterone/oestrogen:Climen
 Drospirenone/oestrogen: Angeliq
 Medroxyprogesterone/oestrogen:Premelle
 Norethisterone/oestrogen:Novofem
 Medroxyprogesterone acetate: Provera
 Progesterone: Cyclogest
 Norgestrel/oestrogen: Postoval
 Ethinylestradiol combinations plus progestogen
 HRT in women without uterus:
 Conjugated oestrogen: Premarin add progestogen
 Ethinylestradiol combinations: menoflush
 Use of oral contraceptives during the menopausal transition — A low-estrogen oral contraceptive (OC) is an
option for perimenopausal women who seek relief of menopausal symptoms, who also desire contraception,
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and who in some instances need control of bleeding when it is heavy
 17 Tibolone

Tibolone is a selective oestrogen receptor modulator (SERM) which combines oestrogenic and
progestogenic activity with weak androgenic activity

I: VSM symptoms ff. natural or surgical menopause

 Prevention of postmenopausal osteoporosis
 C/I: thromboembolic ds/severe liver dsd
 Used >1 year after LNMP can cause irregular vaginal bleeding

 It can be used in women with an intact uterus who have had no bleeding for more than
one year, without the need for cyclical progestogen.
 May improve sexual function and vasomotor symptoms.
 There may be a small increased risk of stroke, endometrial cancer and breast cancer
(including breast cancer recurrence) with tibolone.
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 Tibolone is less effective than combined HRT in alleviating menopausal symptoms.
18 Side Effects of HRT

 Oestrogen: breast tenderness, leg cramps, bloating, nausea, headaches.

 Progestogen: premenstrual syndrome-like symptoms, breast tenderness,
backache, depression, pelvic pain.
 Bleeding: monthly sequential preparations should produce regular,
predictable and acceptable bleeds starting towards the end, or soon after,
the progestogen phase. Breakthrough bleeding is common in the first 3-6
months of continuous combined and long-cycle HRT regimens.

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19 SERM

 Selecive estrogen receptor modulator –non steroidal synthetic agents

whose agonist or antagonist activities on estrogen receptor (ER) are tissue
selective.

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20 SERM DRUGS…

Tamoxifen
Raloxifene
Clomifene citrate
Toremifene

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21 SERM-Raloxifene

 Uses: reduce the risk of invasive oestrogen-dependent breast cancer

 Prevention and treatment of osteoporosis in postmenopausal women
 Mx of anovulatory or oligo-ovulatory infertility in women (intact hypothalamic-pituitary-ovarian axis
 Increased risk of venous thromboembolism
 Lowers the risk of breast cancer in high risk women
 Lowers cholesterol level

MOA: bids to oestrogen receptors and inhibits bone resorption without stimulating the uterine endometrium

DOES NOT RELIEVE THE VASOMOTOR SYMPTOMS OF THE MENOPAUSE

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22 Clomiphene

MOA USES
 Acts as a competitive Estrogen  Infertility due to anovulation
Receptor (ER) the hypothalamus
 Male infertility-oligozoospermia
 Inhibits negative feedback on the
 In vitro fertilization
release of GnRH
 Increases the pulse frequency of
GnRH

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23 Clomiphene
Adverse Effects Dosing
 Multiple pregnancy  50mg daily for 5days starting on
day 3-5 days of menstrual cycle
 Weight gain
 Or after induced bleeding
 Hot flushes
 Polycystic ovarian-withdraw
therapy  On repeat: if ovulation fails,
100mg daily for 5 days
 Reversible ovarian enlargement
 3 courses=adequate
 Reversible alopecia
 Vertigo
 Abnormal uterine bleeding
 CNS Effects: dizziness, depression,
fatigue, insomnia, diplopia,
photophobia, blurring of vision,
lightheadedness 2020/02/23
24

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25 Tamoxifen
Drug Interactions
 Potent CYP2D6 inhibitor-SSRI
reduce tamoxifen effectiveness by
Inhibiting conversion of active
metabolite, endoxifen
Adverse Effects
 Thromboembolic dsd
 Hepatic enzyme change
 Ocular complications
 Malignant uterine tumours
 Ovarian cysts in premenopausal
women
 Hair loss
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26 Case scenario

 60 years old woman presents with amenorrhoea for 2 years.

 What are your thoughts?
 she tells you that she has vasomotor symptoms (hot flushes) associated with
menopause. She has an intact uterus. No significant past medical history
 If you think its menopause, what do you do next?
 Drugs?
 MOA
 Adverse Effects
 . What would you recommend and why?
 Medroxyprogesterone acetate and estradiol orally. You can’t give an
unopposed oestrogen to a woman with an intact uterus. Prevent possible
endometrial hyperplasia with can develop into endometrial cancer.

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